Alzheimer’s disease (AD) is characterized by cognitive impairment and different non-cognitive deficits called “Behavioural and psychological symptoms of dementia” (BPSD) related to neurotrophin alterations, which differ from those presented in normal aging. Mouse models, both transgenics and inbreed mice models of AD, are a useful tool in understanding the underlying mechanisms of the disease. The SAMP8 (senescence-accelerated mouse prone 8) mice line was generated from AKR/J strain by Professor Toshio Takeda at the University of Kyoto. This strain exhibited a particular early-onset and accelerated aging phenotype. The present study characterizes and provides information regarding the non-cognitive, cognitive and neurotrophin alterations and their correlation, demonstrating the AD-like symptoms presented in older males SAMP8. The cognitive impairment presented was accompanied by a reduction in sociability and an increase in aggressive as well as anxiety behaviours. Furthermore, changes in two of the most important neurotrophins, such as brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT3) were found. Thus, the present results reveal new insights in this useful inbred mouse model of neurodegeneration and AD, demonstrating the potential relationship between neurotrophin modifications, cognitive impairment and neuropsychiatric disorders (ND).

The study of complex systems deals with emergent behaviour that arises as a result of nonlinear spatio-temporal interactions between a large number of components both within the system, as well as between the system and its environment. There is a strong case to be made that neural systems as well as their emergent behaviour and disorders, can be studied within the framework of complexity science. In particular, the field of neuroimaging has begun to apply both theoretical and experimental procedures originating in complexity science – usually in parallel with traditional methodologies. Here, we demonstrate that the use of such traditional models may distort the outcomes of neuroimaging experiments – hence affecting their interpretability and raising questions about their reliability.Therefore, we argue in favor of adopting a complex systems-based methodology in the study of neuroimaging, alongside appropriate experimental paradigms, and with minimal influences from non-complex systems approaches. Our exposition includes a review of the fundamental mathematical concepts, combined with practical examples and a compilation of results from the literature.

Monitoring the ratio of forested and deforested areas plays a key role in studying the dynamics of forest areas. Appropriate mapping of anthropogenic forest disturbances is particularly important in the context of sustainable forest management. It provides ecological, social and economic information which is crucial for forest policymakers. In the last two decades, the forest areas of the Moldo-Transylvanian Carpathians have been subject to a high rate of deforestation which at present state lacks proper quantification. We present a novel methodology for monitoring the forest disturbance dynamics in Moldo-Transylvanian Carpathians by use of fractal analysis including entropy, Fractal Fragmentation Index (FFI) and Tug-of-War lacunarity (Λ_(T-o-W)). This was necessary to quantify and identify the disorder (entropy), the fragmentation (FFI) and heterogeneity of the spatial distribution (Λ_(T-o-W)) patterns. Based on satellite images of the forest areas (annually 2000-2014), increased fragmentation was demonstrated by FFI increase, a measure of the degree of disorder (entropy) and heterogeneity (lacunarity). Our results revealed that textural and fractal analysis can be an effective tool for the extraction of quantitative information about the spatiotemporal dynamics of forest disturbance. The methods developed, and results obtained are a complementary approach to forest disturbance mapping (based on traditional image classification) for future development and adaptation of forestry management policies to ensure a sustainable management and exploitation of forest areas.

The functionalization of polymeric substances is of great interest for the development of innovative materials for advanced applications. For many decades, the functionalization of chitosan has been a convenient way to improve its properties with the aim to prepare new materials with specialized characteristics. In the present article, we summarize the latest methods for the modification and derivatization of chitin and chitosan, trying to introduce specific functional groups under experimental conditions, which allow a control over the macromolecular architecture. This is motivated because an understanding of the interdependence between chemical structure and properties is an important condition for proposing innovative materials. New advances in methods and strategies of functionalization such as click chemistry approach, grafting onto copolymerization, coupling with cyclodextrins and reactions in ionic liquids are discussed.

The prevalence of food allergy has increased in recent years, especially in children. Food allergen avoidance and symptomatic drugs in case of an allergic reaction remain the standard of care in food allergy. Nevertheless, increasing attention has been given to the possibility to treat food allergy, through immunotherapy, particularly oral immunotherapy (OIT). Several OIT protocols and clinical trials have been published. Most of them focus on children allergic to milk, egg, or peanuts, although recent studies developed protocols for other foods, such as wheat and different nuts. OIT efficacy in randomized controlled trials is usually evaluated as the possibility for patients to achieve desensitization, while the issue of a possible long-term sustained unresponsiveness has not been completely addressed. Here, we evaluated current OIT knowledge, focusing on the results of clinical trials and current guidelines. Specifically, we wanted to highlight what is known in terms of OIT efficacy and effectiveness, safety, and impact on quality of life. For each aspect, we reported the pros and the cons, inferable from published literature. In conclusion, even though many protocols, reviews and meta-analysis have been published on this topic, OIT remains a controversial therapy and no definitive generalized conclusion may be drawn so far. It should be an option provided by specialized teams, when both patients and their families are prone to adhere to the proposed protocol. Efficacy, long-term effectiveness, possible role of adjuvant therapies, risk of severe reactions including anaphylaxis or eosinophilic esophagitis, and impact on the quality of life of both children and caregivers are all aspects that should be discussed before starting OIT. Future studies are needed to provide firm clinical and scientific evidence, which should also consider patient reported outcomes.

Agricultural Production today has to deal with different challenges. It has to increment production for a continuously increasing population, reducing the environmental burdens on the natural systems. In conventional agriculture, this is possible through the increase of inputs, especially nutrients, which, however, are responsible for the biggest part of emissions. It becomes more complicated though, adopting sustainable agricultural practices, to improve the quality and the quantity of agricultural production reducing the inputs use. Plant growth regulators are described in the literature for the significant role in securing crop management of modern agriculture. Therefore, this joint field experiment has been carried out on a pear orchard (Pyrus communis L. cv. Abate Fètel) in Emilia Romagna (Italy) by Fondazione Navarra and TIMAC AGRO Italia S.p.A., to test the “less for more” theory which consists in getting more and better agricultural produce using fewer inputs. Preliminary results of two consecutive years have confirmed our assumption as it was possible to substantially reduce the total fertilisation units applied, improving significantly quantitative and qualitative production indicators (i.e. flower and fruit density, fruit set (%), the average weight of fruits (g) and the total yield (t/ha)). Results have also shown a positive correlation between plant growth regulators and agronomic efficiency of pears.

Pathogen genomics is a critical tool for public health surveillance, infection control, outbreak investigations, as well as research. In order to make use of pathogen genomics data, it must be interpreted using contextual data (metadata). Contextual data includes sample metadata, laboratory methods, patient demographics, clinical outcomes, and epidemiological information. However, the variability in how contextual information is captured by different authorities and how it is encoded in different databases poses challenges for data interpretation, integration, and its use/re-use. The DataHarmonizer is a template-driven spreadsheet application for harmonizing, validating, and transforming genomics contextual data into submission-ready formats for public or private repositories. The tool’s web browser-based JavaScript environment enables validation and its offline functionality and local installation increases data security. The DataHarmonizer was developed to address the data sharing needs that arose during the COVID-19 pandemic, and was used by members of the Canadian COVID Genomics Network (CanCOGeN) to harmonize SARS-CoV-2 contextual data for national surveillance and for public repository submission.In order to support coordination of international surveillance efforts, we have partnered with the Public Health Alliance for Genomic Epidemiology to also provide a template conforming to its SARS-CoV-2 contextual data specification for use worldwide. Templates are also being developed for One Health and foodborne pathogens. Overall, the DataHarmonizer tool improves the effectiveness and fidelity of contextual data capture as well as its subsequent usability. Harmonization of contextual information across authorities, platforms and systems globally improves interoperability and reusability of data for concerted public health and research initiatives to fight the current pandemic and future public health emergencies. While initially developed for the COVID-19 pandemic, its expansion to other data management applications and pathogens is already underway.

The World Health Organization has defined the outbreak of the new coronavirus as a public health emergency of international concern. The average age of patients affected by the disease caused by the virus ranges from 49 to 59 years. The symptoms of coronavirus disease 2019 (COVID-19) infection include fever, cough, acute respiratory disease, and, in severe cases, the disease may progress to pneumonia and renal failure that may lead to death. Many oral and maxillofacial hospital procedures produce aerosol and droplets contaminated by blood, bacteria, and viruses. The purpose of this study is to gather recommendations from health authorities and scientific articles in order to educate surgeons regarding the procedures to assist and treat in oral and maxillofacial surgeries. The objective is to prevent the transmission of COVID-19 during the treatment of patients in urgent and emergency situations. The study’s methodology used the guidelines provided by the Brazilian College of Oral and Maxillofacial Surgery, in addition to the recommendations and epidemiologic data from national and international health authorities. The implementation of special precautions in oral and maxillofacial surgeries may elucidate questions related to the transmission of the disease by asymptomatic carriers and help control the spread of the virus.

Flavonoids are widely recognized as natural polydrugs, given their anti-inflammatory, antioxidant, sedative and antineoplastic activities. Recently, different studies have shown that flavonoid have the potential to inhibit BET bromodomains. Previous reports suggest that flavonoids are putative inhibitors of the ZA channel due to their orientation and interactions with P86, V87, L92, L94 and N140. Herein, a comprehensive characterization of the binding mode of the biflavonoid amentoflavone and fisetin is discussed. To this end, both compounds were docked with BRD4 using four docking programs. Results were post-processed with protein-ligand interaction fingerprints. To gain further insights into the binding mode of the two natural products, docking results were further analyzed with molecular dynamics. Results showed that amentoflavone makes numerous contacts in the ZA channel, as previously described for flavonoids and kinase inhibitors. It was also found that amentoflavone can potentially make contacts with non-canonical residues for BET inhibition. Most of these contacts were not observed with fisetin. Based on these results, amentoflavone was tested for BRD4 inhibition, showing activity in the micromolar range. This work may serve as basis for scaffold optimization and further characterization of flavonoids as BET inhibitors.

This paper investigates the mental health stressors experienced by Central American youth immigrants and asylum seekers, including unaccompanied minors, surveyed in the U.S. in 2017. This population is hard to reach, vulnerable, and disproportionately exposed to trauma from a young age. They face numerous challenges to mental health, and increased psychopathological risk, exacerbated by high levels of violence and low state-capacity in sending countries, restrictive immigration policies, the fear of deportation for themselves and their family members, and the pressure to integrate once in the U.S. Using survey data and the validated PHQ-9 questionnaire and Child PTSD Symptom Scale (CPSS), we find that Central American youth have seen improvements in their self-reported mental health after migrating to the U.S. but remain at risk of further trauma exposure, depression, and PTSD. They exhibit a disproportionate likelihood of having lived through traumatizing experiences that put Central American immigrants at higher risk for psychological distress and disorders and may also create obstacles to integration that in turn create new stressors that compound with PTSD and depression. PTSD, depression, or anxiety can be minimized through programs that aid their integration and mental health.

This paper presents a review of the electrical heating method for heavy oil recovery based on past, current, and future prospects of electrical heating. Heavy oil is one of the potential crude oil used as a link to reduce the crisis of light oil used today. The obstacle of heavy oil is a high viscosity and density in which thermal injection is a method for heavy oil recovery, but it results in economic and environmental issues. Electrical heating is one of the thermal methods by transferring heat into the reservoir. The basic process of electrical heating is to increase the mobility of the oil. Because the temperature rises, it can reduce oil viscosity and makes it easier for heavy oil to flow. The past and current developments have been carried out to fill up the gap of electrical heating projects. The future prospects must meet energy efficiency, and the excessive heat will damage formation that must be tackled in the future prospect. the works adopt several electrical heating projects and applications in the world where the works give a brief future prospect of electrical heating.

The aim of this work is the preparation of contact active antimicrobial films by blending copolymers with quaternary ammonium salts and polyacrylonitrile as matrix material. A series of copolymers based on acrylonitrile and methacrylic monomers with quaternizable groups were designed with the purpose of investigating the influence of their chemical and structural characteristics on the antimicrobial activity of these surfaces. The biocide activity of these systems was studied against different microorganisms, such as the Gram-positive bacteria Staphylococcus aureus and the Gram-negative bacteria Pseudomona aeruginosa and the yeast Candida parapsilosis. The results confirmed that parameters such as flexibility and polarity of the antimicrobial polymers immobilized on the surfaces strongly affect the efficiency against microorganisms. In contrast to the behavior of copolymers in water solutions, when they are tethered to the surface, the active cationic groups are less accessible and then the mobility of the side chain is critical for a good contact with the microorganism. Blend films composed of copolymers with high positive charge density and chain mobility present up to a more than 99.999% killing efficiency against the studied microorganisms.

Music and language are hypothesized to share neural resources, particularly at the level of syntax processing. Recent reports suggest that attention modulates this sharing of neural resources, but the time-course of the effects of attention, and the degree to which attention operates similarly on music and language, are yet unclear. In this EEG study we manipulate the syntactic structure of simultaneously presented musical chord progressions and garden-path sentences in a modified rapid serial visual presentation paradigm, while varying top-down attentional demands to the two modalities. The Early Right Anterior Negativity (ERAN) was observed in response to both attended and unattended musical syntax violations. In contrast, an N400 was only observed in response to attended linguistic syntax violations, and a P3 only in response to attended musical syntax violations. Results show that top-down allocation of attention indeed affects the processing of syntax in both music and language, with different neural resources acting upon the two modalities particularly at later stages of cognitive processing. However, the processing of musical syntax at an earlier stage of the perceptual-cognitive pathway, as indexed by the ERAN, is partially automatic, and is strongly indicative of separate neural resources for music and language.

In this article we review the advances that have been made on the understanding of the high-pressure structural, vibrational, and electronic properties of wolframite-type oxides since the first works in the early 1990s. Mainly tungstates, which are the best known wolframites, but also tantalates and niobates, with an isomorphic ambient-pressure wolframite structure, have been included in this review. Apart from estimating the bulk moduli of all known wolframites; the cation-oxygen bond distances and their change with pressure have been correlated with their compressibility. The composition variations of all wolframites have been employed to understand their different structural phase transitions to post-wolframite structures as a response to high pressure. The number of Raman modes and band gap energy changes have been also analyzed in the basis of these compositional differences. The reviewed results are relevant for both fundamental science and for the development of wolframites as scintillating detectors. The possible next research venues of wolframites have also been evaluated.

Low-temperature processed ITO thin films offer the potential of overcoming the doping limit by suppressing the equilibrium of compensating oxygen interstitial defects. To elucidate this potential, electrical properties of Sn-doped In₂O₃ (ITO) thin films are studied in dependence on film thickness. In-operando conductivity and Hall effect measurements during annealing of room temperature deposited films with different film thickness in different environments allow to discriminate between the effects of crystallization, grain growth, donor activation and oxygen diffusion on carrier concentrations and mobilities. At 200 °C, a control of carrier concentration by oxygen incorporation or extraction is only possible for very thin films. The electrical properties of thicker films deposited at room temperature are mostly affected by grain size. The remaining diffusivity of compensating oxygen defects at 200 °C is sufficient to screen the high Fermi level induced by deposition of Al₂O₃ using atomic layer deposition (ALD), which disables the use of defect modulation doping at this temperature. The results indicate that achieving higher carrier concentrations requires a control of the oxygen pressure during deposition in combination with seed layers to enhance crystallinity or the use of near room temperature ALD.

Primary varicella-zoster virus (VZV) infection causes varicella (chickenpox) and the establishment of a lifelong latent infection in ganglionic neurons. VZV reactivates in about one-third of infected individuals to cause herpes zoster, often accompanied by neurological complications. The restricted host range of VZV and, until recently, the lack of suitable in vitro models to study VZV latency have seriously hampered molecular studies of viral latency. Nevertheless, recent technological advances facilitated a series of exciting studies that resulted in the discovery of a VZV latency-associated transcript (VLT) and have redefined our understanding of VZV latency and factors that initiate reactivation. Together, these findings pave the way for a new era of research that may finally unravel the precise molecular mechanisms that govern latency. In this review, we will summarize the implications of recent discoveries in the VZV latency field from both a virus and host perspective and provide a roadmap for future studies.

Pipeline integrity is an important area of concern for the oil and gas, refining, chemical, hydrogen, carbon sequestration, and electric-power industries, due to the safety risks associated with pipeline failures. Regular monitoring, inspection, and maintenance of these facilities is therefore required for safe operation. Large standoff magnetometry (LSM) is a non-intrusive, passive magnetometer-based mea- surement technology that has shown promise in detecting defects (anomalies) in regions of elevated mechanical stresses. However, analyzing the noisy multi-sensor LSM data to clearly identify regions of anomalies is a significant challenge. This is mainly due to the high frequency of the data collection, mis-alignment between consecutive inspections and sensors, as well as the number of sensor measurements recorded. In this paper we present LSM defect identification approach based on ma- chine learning (ML). We show that this ML approach is able to successfully detect anomalous readings using a series of methods with increasing model complexity and capacity. The methods start from unsupervised learning with "point" methods and eventually increase complexity to supervised learning with sequence methods and multi-output predictions. We observe data leakage issues for some methods with randomized train/test splitting and resolve them by specific non-randomized splitting of training and validation data. We also achieve a 200x acceleration of support-vector classifier (SVC) method by porting computations from CPU to GPU leveraging the cuML RAPIDS AI library. For sequence methods, we develop a customized Convolutional Neural Network (CNN) architecture based on 1D convolutional filters to identify and characterize multiple properties of these defects. In the end, we report the scalability of the best-performing methods and compare them, for viability in field trials.

Thanks to advanced semiconductor microfabrication technology, chip-scale integration and miniaturization of lab-on-a-chip components, silicon-based optical biosensors have made significant progress for the purpose of point-of-care diagnosis. In this review, we provide an overview of the state-of-the-art in evanescent field biosensing technologies including interferometer, microcavity, photonic crystal, and Bragg grating waveguide-based sensors. Their sensing mechanisms and sensor performances, as well as real biomarkers for label-free detection, are exhibited and compared. We also review the development of chip-level integration for lab-on-a-chip photonic sensing platforms, which consist of the optical sensing device, flow delivery system, optical input and readout equipment. At last, some advanced system-level CMOS-chip packaging examples are presented, indicating the commercialization potential for the low cost, high yield, portable biosensing platform leveraging CMOS processes.

There is high prevalence of hypertension and is rapidly increasing around the world, despite the intervention programme implemented, this study aimed at estimating the prevalence rate, test of association between hypertension and risk factors and model hypertension rate. Data used was obtained from the health record of Federal Medical Centre, Keffi from January 2016 – January 2019. Ordinal logistic regression model was used; Model Fitting Information, Goodness-of-Fit, Pseudo R-Square and Test of Parallel Lines are fitted to the data sets to test the accuracy and correctness of the model. The results indicated that the overall prevalence of hypertension rate is high at 36.4%, among the adult population, body mass index and gender are statistically significant, and Age is not significant in the study. Individuals that are overweight are more likely to be hypertensive compare to other weights. At age 40 – 49 years which have the highest rate of 26.5% and the odd ratio is 0.75 compared to others. One year increase in age 30 – 39, the cumulative odd of being hypertensive is 0.91 while other independent variables are held constant. The odd ratio of female being hypertensive is 0.85, therefore the females are more likely to be hypertensive with 54.4% compared to the males at 45.6% . There is no presence of multicolinearity among the variables and Logit models were formulated to calculate probabilities of the various possible outcomes.

Remote sensing data are essential for monitoring Earth’s surface waters, especially since the number of publicly available in-situ data is declining. Satellite altimetry provides valuable information on water level and its variations for lakes, reservoirs, and rivers. In combination with satellite imagery, the derived time series allow for monitoring lake storage changes and river discharge. However, satellite altimetry is limited in spatial resolution due to its measurement geometry, only providing information in nadir direction beneath the satellite’s orbit. In a case study in the Mississippi River Basin (MRB), this study investigates the potential and the limitations of past and current satellite missions to monitor basin-wide storage changes. For that purpose an automated target detection is developed and the extracted lake surfaces are merged with the satellites’ tracks. This reveals that the current altimeter configuration misses about 80% of all lakes larger than 0.1 km2 in the MRB, and still 20% of lakes larger than 10 km2, corresponding to 30% and 7% of surface area, respectively. Past altimetry configurations perform even worse. From the water bodies represented by a global hydrology model, at least 91% of targets and 98% of storage changes are captured by the current altimeter configuration. This will significantly improve with the launch of the planned SWOT mission.

We report the influence of ammonium hydroxide (NH4OH), as growth additive, on zinc oxide nanomaterial through the optical response obtained by photoluminescence (PL). A low-temperature hydrothermal process is employed for the growth of ZnO nanowires (NWs) on seedless Au surface. A more than two order of magnitude change in ZnO NW density is demonstrated via careful addition of NH4OH in the growth solution. Further, we show by systematic experimental study and PL characterization data that the addition of NH4OH can degrade the optical response of ZnO NWs produced. The increase of growth solution basicity with the addition of NH4OH may slowly degrade the optical response of NWs by slowly etching its surfaces, increasing the point defects in ZnO NWs. The present study demonstrates the importance of growth nutrients to obtain quality controlled density tunable ZnO NWs on seedless conducting substrates.

Introduction: Clinicians have been struggling with the optimal diagnostic approach of patients with suspected COVID-19. We evaluated the added value of chest CT over RT-PCR alone. Methods: Consecutive adult patients with suspected COVID-19 presenting to the emergency department (Academic Medical Center, Amsterdam University Medical Centers, the Netherlands) from March 16^th to April 16^th were retrospectively included if they required hospital admission and underwent chest CT and RT-PCR testing for SARS-CoV-2 infection. The CO-RADS classification was used to assess the radiological probability of COVID-19, where a score of 1-2 was considered as negative, 3 as indeterminate, and 4-5 as positive. CT results were stratified by initial RT-PCR results. For patients with a negative RT-PCR but a positive CT, serology or multidisciplinary discussion after clinical follow-up constituted the final diagnosis. Results: 258 patients with suspected COVID-19 were admitted, of which 239 were included because they had both CT and RT-PCR testing upon admission. Overall, 112 patients (46.9%) had a positive initial RT-PCR, and 14 (5.9%) had a positive repeat RT-PCR. Of 127 patients with a negative or indeterminate initial RT-PCR, 38 (29.9% [95%CI 21.3-39.3%]) had a positive CT. Of these, 13 had a positive RT-PCR upon repeat testing, and 5 had positive serology. The remaining 20 patients were assessed in a multidisciplinary consensus meeting, and for 13 it was concluded that COVID-19 was ‘very likely’. Of 112 patients with a positive initial RT-PCR result, CT was positive in 104 (92.9% [95%CI 89.3-97.5%]). Conclusion: In a high-prevalence emergency department setting, chest CT showed high probability of COVID-19 (CO-RADS 4-5) in 29.9% of patients with a negative or indeterminate initial RT-PCR result. As the majority of these patients had proven or ‘very likely’ COVID-19 after follow-up, we believe that CT helps in the identification of patients who should be admitted in isolation.

Following the general aim of recapitulating the native mechanical properties of tissues and organs in vitro, the field of materials science and engineering has benefited from recent progress in developing compliant substrates with similar physical and chemical properties. In particular, in the field of mechanobiology, soft hydrogels can now reproduce the precise range of stiffnesses of healthy and pathological tissues to study the mechanisms behind cell response to mechanics. However, it was shown that biological tissues are not only elastic but also relax at different timescales. Cells can indeed perceive and actually need this dissipation because it is a critical signal integrated with other signals to define adhesion, spreading and even more complicated functions. The mechanical definition of hydrogels used in mechanobiology is however commonly limited to the elastic stiffness (Young’s modulus) and this value is known to depend greatly on the measurement conditions that are rarely reported. Here, we report that a simple relaxation test performed under well defined conditions can provide all the necessary information to characterize soft materials mechanically, by fitting the dissipation behavior with a generalized Maxwell model (GMM). The method was validated using soft polyacrylamide hydrogels and proved to be very useful to unveil precise mechanical properties of gels that cells can sense and offer a set of characteristic values that can be compared with what is typically reported from microindentation tests.

The increasing complexity of the design and operation evaluation process of multi-energy grids (MEGs) requires tools for the coupled simulation of power, gas and district heating grids. Most tools analyzed in this paper either do not allow coupling of infrastructures, simplify the grid model or are not publicly available. We introduce the open source piping grid simulation tool pandapipes that – in interaction with pandapower - fulfills three crucial criteria: clear data structure, adaptable MEG model setup and performance. In an introduction to pandapipes we illustrate how it fulfills these criteria through its internal structure and demonstrate how it performs in comparison to STANET®. Then we show two case studies that have been performed with pandapipes already. The first case study demonstrates a peak shaving strategy as interaction of a local electricity and district heating grid in a small settlement. The second case study analyzes the potential of a power-to-gas device to serve as flexibility in a power grid under consideration of gas grid constraints. They both show the importance of a clear database, a simple simulation setup and good performance to set up different large and complex studies on grid infrastructure design and operation.

Survival following Ebola virus (EBOV) infection correlates with the ability to mount an early and robust interferon (IFN) response. The host IFN-induced proteins that contribute to controlling EBOV replication are not fully known. Among the top genes with the strongest early increases in expression after infection in vivo is IFN-induced HERC5. Using a transcription- and replication-competent VLP system, we showed that HERC5 inhibits EBOV virus-like particle (VLP) replication by depleting EBOV mRNAs. The HERC5 RCC1-like domain was necessary and sufficient for this inhibition and did not require zinc finger antiviral protein (ZAP). Moreover, we showed that EBOV (Zaire) glycoprotein (GP) but not Marburg virus GP antagonized HERC5 early during infection. Our data identifies a novel ‘protagonist-antagonistic’ relationship between HERC5 and GP in the early stages of EBOV infection that could be exploited for the development of novel antiviral therapeutics.

Scrub typhus threatens one billion people in the Asia-Pacific area and cases have emerged outside this region. It is caused by infection with any of the multitude of strains of the bacterium, Orientia tsutsugamushi. A vaccine that affords heterologous protection and a commercially available molecular diagnostic assay are lacking. Herein, we determined that the nucleotide and translated amino acid sequences of outer membrane protein A (OmpA) are highly conserved among 51 O. tsutsugamushi isolates. Molecular modeling revealed the predicted tertiary structure of O. tsutsugamushi OmpA to be very similar to that of the phylogenetically related pathogen, Anaplasma phagocytophilum, including the location of a helix that contains residues functionally essential for A. phagocytophilum infection. PCR primers were developed that amplified ompA DNA from all O. tsutsugamushi strains, but not from negative control bacteria. Using these primers in quantitative real-time PCR enabled sensitive detection and quantitation of O. tsutsugamushi ompA DNA from organs of mice that had been experimentally infected with the Karp or Gilliam strains. The high degree of OmpA conservation among O. tsutsugamushi strains evidences its potential to serve as a molecular diagnostic target and justifies its consideration as a candidate for developing a broadly protective scrub typhus vaccine.

All infections are potentially curable as long as the etiological agents are susceptible to antimicrobials. The increased rate at which antimicrobials are becoming ineffective is a global health risk of increasing concern that threatens withdrawal of beneficial antimicrobials for disease control. Increased demand for food of animal origin, in particular eggs, meat and milk has led to intensification and commercial production systems where excessive use and misuse of antimicrobials may prevail. Antimicrobials, handled and used by farmers and animal attendants with no formal education may predispose to incorrect dosages, misuse, incorrect applications and non-adherence to withdrawal periods. A multimethod approach (desk review, field study and interviews) was used. Relevant establishments were also visited. High levels of resistance to penicillin G, chloramphenicol, streptomycin and oxytetracycline have been reported especially for Actinobacter pyogenes, Staphylococcus hyicus, Staphylococcus intermedius and Staphylococcus aureus from dairy cattle with mastitis and in humans. Similar trends were found in poultry where eggs and meat are contaminated with Escherichia coli strains resistant to amoxicillin + clavulanate, sulphamethoxazole and neomycin. An increasing trend of emerging multidrug resistant E. coli, Klebsiella pneumoniae, Staphylococcus aureus, and Salmonella was also found in food animals. An in-crease in methicillin resistant Staphlococcus aureus (MRSA) and extended-spectrum beta-lactamase (ESBL) in the livestock sector in Tanzania have been reported. Specific antimicrobials resistant to were ampicillin, augmentin, gentamicin, cotrimoxazole, tetracycline, amoxicillin, ampicillin, gentamicin, streptomycin, erythromycin, tetracycline, ciprofloxacin, nalidixic acid, azithromycin, chloramphenicol, tylosin, erythromycin, cefuroxime, norfloxacin and ciprofloxacin. An in-creased usage of antimicrobials for prophylaxis, anaphylaxis and therapeutics against pathogens and for growth promotion in livestock, aquaculture and crops production were observed. One Health strategic approach is advocated to combat AMR in the food and agriculture sectors in Tanzania. Practical recommendations include a) legislation review and implementation, b) AMU, AMR and AR awareness and advocacy among stakeholders along the value chain, c) strengthening of surveillance and monitoring programs for AMU, AMR and AR, d) enhance development and use of rapid and innovative diagnostic tests and promotion biosecurity principles and e) good husbandry practices. The utilization of this information to improve public health policies and reduce the burden of AMR will be beneficial.

Patients with chronic obstructive pulmonary disease (COPD) often require frequent hospitalization due to worsening symptoms. Preventing prolonged hospital stay and readmission becomes a challenge for healthcare professionals treating patients with COPD. Although the integration of health and social care supports greater collaboration and enhanced patient care, organizational structure and poor leadership may hinder the implementation of patient-oriented goals. This paper presents a case of a 64-year-old chronic smoker with severe COPD who was to be discharged on long-term oxygen therapy (LTOT). It further highlights the healthcare decisions made to ensure the patient’s safety at home and further provides a long-lasting solution to the existing medical and social needs. The goal was accomplished through a discharge plan that reflects multidisciplinary working, efficient leadership, and change management using Havelock’s theory. While COPD is characterized by frequent exacerbation and hospital readmission, it was emphasized that most failed discharges could be attributed to bureaucratic organizational workflow which might not be in the patient’s best interest. It was further demonstrated that healthcare professionals are likely to miss the window of opportunity to apply innovative and long-lasting solutions to the patient’s health condition in an attempt to remedy the immediate symptoms of COPD

The Lewy Body Dementia Association (LBDA) held a virtual event, the LBDA Biofluid/Tissue Biomarker Symposium, on January 25, 2021, to present advances in biomarkers for Lewy Body Dementia (LBD), which includes Dementia with Lewy Bodies (DLB) and Parkinson's Disease Dementia (PDD). The meeting featured eight internationally known scientists from Europe and the United States and attracted over 200 scientists and physicians from academic centers, the National Institutes of Health and the pharmaceutical industry. Methods for confirming and quantifying the presence of Lewy body and Alzheimer pathology as well as novel biomarkers were discussed.

This paper presents a novel micro-segmented genetic algorithm (μsGA) to identify the best solution for the locomotion of a quadruped robot designed on a rectangular ABS plastic platform. We compare our algorithm with three similar algorithms found in the specialized literature: a standard genetic algorithm (GA), a micro-genetic algorithm (μGA), and a micro artificial immune system (μAIS). The quadruped robot prototype guarantees the same conditions for each test. The platform was developed using 3D printing for the structure and can accommodate the mechanisms, sensors, servomechanisms as actuators. It also has an internal battery and a multicore embedded system (mES) to process and control the robot locomotion. This research proposes a μsGA that segments the individual into specific bytes. μGA techniques are applied to each segment to reduce the processing time; the same benefits as the GA are obtained, while the use of a computer and the high computational resources characteristic of the GA are avoided. This is the reason why some research in robot locomotion is limited to simulation. The results show that the performance of μsGA is better than the three other algorithms (GA, μGA and AIS). The processing time was reduced using a mES architecture that enables parallel processing, meaning that the requirements for resources and memory were reduced. This research solves the problem of continuous locomotion of a quadruped robot, and gives a feasible solution with real performance parameters using a μsGA bio-micro algorithm and a mES architecture.

Synthesis and characterization of anhydrous LiZn(IO₃)₃ powders prepared from an aqueous solution are reported. Morphological and compositional analyses were carried out by scanning electron microscopy and energy dispersive X-ray measurements. The synthesized powders exhibit a needle-like morphology after annealing at 400°C. A crystal structure for the synthesized compound has been proposed from powder X-ray diffraction and density-functional theory calculations. Rietveld refinements led to a monoclinic structure, which can be described with space group P21, number 4, and unit-cell parameters a = 21.874(9) Å, b = 5.171(2) Å, c = 5.433(2) Å, and beta = 120.93(4)º. Density-functional theory calculations supported the same crystal structure. Infrared spectra were also collected and the vibrations associated to the different modes discussed. The non-centrosymmetric space group determined for this new polymorph of LiZn(IO₃)₃, the characteristics of its infrared absorption spectrum, and the observed second harmonic generation suggest a promising infrared non-linear optical material.

Hepatotoxic microcystins (MCs) are the most widespread class of cyanotoxins and the one that has most often been implicated in cyanobacterial toxicosis. One of the main challenges in studying and monitoring MCs is the great structural diversity within the class. The full chemical structure of the first MC was elucidated in the early 1980s and since then the number of reported structural analogues has grown steadily and continues to do so, thanks largely to advances in analytical methodology. The structures of some of these analogues have been definitively elucidated after chemical isolation using a combination of techniques including nuclear magnetic resonance, amino acid analysis and tandem mass spectrometry (MS/MS). Others have only been tentatively identified using liquid chromatography-MS/MS without chemical isolation. An understanding of the structural diversity of MCs, the genetic and environmental controls for this diversity and the impact of structure on toxicity are all essential to the ongoing study of MCs across several scientific disciplines. However, because of the diversity of MCs and the range of approaches that have been taken for characterizing them, comprehensive information on the state of knowledge in each of these areas can be challenging to gather. We have conducted an in-depth review of the literature surrounding the identification and toxicity of known MCs and present here a concise review of these topics. At present, at least 269 MCs have been reported. Among these, about 20% (54 of 269) appear to be the result of chemical or biochemical transformations of MCs that can occur in the environment or during sample handling and extraction of cyanobacterial, including oxidation products, methyl esters, or post-biosynthetic metabolites. The toxicity of many MCs has also been studied using a range of different approaches and a great deal of variability can be observed between reported toxicities, even for the same congener. This review will help clarify the current state of knowledge on the structural diversity of MCs as a class and the impacts of structure on toxicity, as well as to identify gaps in knowledge that should be addressed in future research.

This paper describes a novel thruster fault-tolerant control system (FTC) for open-frame remotely operated vehicles (ROVs). The proposed FTC consists of two subsystems: a model-free thruster fault detection and isolation subsystem (FDI) and a fault accommodation subsystem (FA). The FDI subsystem employs fault detection units (FDUs), associated with each thruster, to monitor their state. The robust, reliable and adaptive FDUs use a model-free pattern recognition neural network (PRNN) to detect internal and external faulty states of the thrusters in real time. The FA subsystem combines information provided by the FDI subsystem with predefined, user-configurable actions to accommodate partial and total faults and to perform an appropriate control reallocation. Software-level actions include penalisation of faulty thrusters in solution of control allocation problem and reallocation of control energy among the operable thrusters. Hardware-level actions include power isolation of faulty thrusters (total faults only) such that the entire ROV power system is not compromised. The proposed FTC system is implemented as a LabVIEW virtual instrument (VI) and evaluated in virtual (simulated) and real-world environments. The proposed FTC module can be used for open frame ROVs with up to 12 thrusters: eight horizontal thrusters configured in two horizontal layers of four thrusters each, and four vertical thrusters configured in one vertical layer. Results from both environments show that the ROV control system, enhanced with the FDI and FA subsystems, is capable of maintaining full 6 DOF control of ROV in the presence of up to 6 simultaneous total faults in the thrusters. With the FDI and FA subsystems in place the control energy distribution of the healthy thrusters is optimised so that the ROV can still operate in difficult conditions under fault scenarios.

Here we evaluate the chemistry of mineral soil solutions collected by suction lysimeters in a small mountain catchment that was affected by acidification-related spruce die-back. The aim was to obtain new insights into spatial patterns of nutrient partitioning during acidification recovery. This was achieved by comparing nutrient concentrations in soil solutions, collected along a V-shaped valley, with those in runoff. Five nests of suction lysimeters were installed in the 33-ha UDL catchment at different topographic positions (hilltops, slopes and valley). Following a 1-year equilibration, monthly samples of soil solutions were collected over a 2-year period. In the vicinity of each lysimeter nest, soil pits were excavated for a study of soil chemistry. Soil solutions were analyzed for SO42-, NO3-, DOC, NH4+, Na+, K+, Ca2+, Mg2+, and total dissolved Al concentrations, DOC and pH. For a P release estimation, ammonium oxalate extraction of soil samples was performed. Comparison of soil water data from this study with other European studies indicated that major environmentally relevant chemical species at UDL had concentrations similar to median concentrations across numerous previously acidified sites. CEC (≤ 58 meq kg-1) and BS (≤ 13 %), however, were significantly lower at UDL than at other European sites, documenting incomplete recovery from acidification. Spatial trends and seasonality in soil water chemistry support belowground inputs from mineral-stabilized legacy pollutants and soil nutrients. Seasonal variability of soil water sulfate and nitrate was significant. High nitrate in soil solutions during summer originated during the preceding dormant season, and high sulfate concentrations observed during the winter originating from recycled organic S during the summer. Higher concentrations of SO42-, NO3-, and base cations in runoff than in soil solutions may be explained by lateral surficial runoff leaching pollutants and nutrients from very shallow soil horizons. Nearly 30 years after peak acidification, solutions in mineral subsoil at UDL exhibited similar concentrations of SO42-, Ca2+ and Mg2+ as median values at the Pan-European International Co-operative Program (ICP) Forest sites, yet NO3- concentrations were an order of magnitude higher than the ICP sites. Calcium applied on soil surface by liming 32 to 11 years ago affected runoff more than soil solutions, suggesting contribution of both shallow soil water and groundwater to runoff.

The key anthropogenic effects on climate include the changes in land use and emission of greenhouse gases into the atmosphere. Depletion of vegetation poses serious threat that speeds the process of climate change and reduces carbon sequestration by the environment. Thus, the preservation of natural environment in urban areas is an essential component of the garden city model, proposed by Sir Ebenezer Howard in 1898, to ensure ecological balance. Recent Landsat images showed that Kumasi does not have the required percentage of green vegetation as was stipulated in the garden city model on which the city was built. It was observed that most parts of Kumasi's green vegetation have been lost to built environments. This study was conducted to assess the impact of urbanization on the garden city status and its effect on the micro-climate of the city. Significant changes in the vegetation cover of the city was evaluated from Landsat-TM imagery and analysis of a long term climatic data of Kumasi carried out over a 55-year period (1960 to 2015). It was observed that, climatic conditions have slightly changed, as mean surface temperature of has increased by 1.2 °C/ 55 years, due to the significant landuse changes from development of non-transpiring, reduced evaporative urban surfaces. However, the impact is not greatly felt due to the geographical location of the city on the globe despite the evidence of a considerable temperature change. Green vegetation conservation for the city is recommended as a top priority in future for city authorities and planners.

Temperature field is an essential attribute of metal additive manufacturing in view of its bearings on the prediction, control, and optimization of residual stress, part distortion, fatigue, balling effect, etc. This work provides an analytical physics-based approach to investigate the effect of scan strategy parameters including time delay between two irradiations and hatching space on thermal material properties and melt pool geometry. This approach is performed through the analysis of the distribution of material properties and temperature profile in three-dimensional space. The moving point heat source approach is used to predict the temperature field. To predict the temperature field during the additive manufacturing process some important phenomena are considered. 1) Due to the high magnitude of temperature in the presence of the laser, the temperature gradient is usually high which has a crucial influence on thermal material properties. Consequently, the thermal material properties of stainless steel grade 316L are considered to be temperature-dependent. 2) Due to the repeated heating and cooling, part usually undergoes several melting and solidification cycles. This physical phenomenon is considered by modifying the heat capacity using the latent heat of melting. 3) The multi-layer aspect of metal AM process is considered by incorporating the temperature history from the previous layer since the interaction of the successive layers has an impact on heat transfer mechanisms. 4) Effect of heat affected zone on thermal material properties is considered by the superposition of material properties in regions where the temperature fields of two consecutive irradiations have an overlap since the consecutive irradiations change the behavior of the material properties. The goals are to 1) investigate the effects of temperature-sensitive material properties and constant material properties on the temperature field. 2) Study the behavior of thermal material properties under different scan strategies. 3) Study the importance of considering the effect of heat affected zone on thermal material through the prediction of melt pool geometry. 4) Investigate the effect of hatching space on melt pool geometry. This work is purely employed physics-based analytical models to predict the behavior of material properties and temperature field under different process conditions, and no finite element modeling is used.

Gastroenteritis cases associated with non-toxigenic strains of Vibrio parahaemolyticus have been reported in many countries, suggesting the contribution of novel virulence factors. One candidate is zonula occludens toxin (Zot), which increases the intestinal permeability by other bacteria. Recently we identified prophages belonging to the Inoviridae family encoding putative Zot-like toxins in Chilean strains. Based on this information we performed sequence-based analyses of these toxins, followed by phylogenetic and structural analyses using computational tools. Our results showed that Zots found in Chilean V. parahaemolyticus strains are grouped into three different phylogenetic clusters, sharing two conserved motifs (Walker A and B) in their N-terminal region. These motifs are also conserved in Zots from the human pathogens Vibrio cholerae, Neisseria meningitidis and Campylobacter concisus. Although Zots of V. parahaemolyticus do not possess the FCIGRL sequence responsible for the effects produced by V. cholerae, they do possess a conserved secondary structure within their C-terminal region with Zots proteins able to disrupt the intestinal barrier, which is interesting since it has been suggested that the structure and not the Zot sequence would be responsible for the biological effects. This preliminary study provides the basis to study the function of Zots found in V. parahaemolyticus on the intestinal barrier and their possible role as a virulence factor.

The building sector has a big potential to reduce the material resource demand needed for building construction and therefore, greenhouse gas (GHG) emissions. Digitalisation can help to make use of this potential and improve sustainability throughout the entire building’s life cycle. One way to address this potential is through the integration of Life-Cycle Assessment (LCA) into the building process by employing Building Information Modelling (BIM). BIM can reduce the effort needed to carry out an LCA and therefore facilitate the integration into the building process. A review of current industry practice and scientific literature shows two main approaches to address BIM-LCA integration. Either the LCA is performed in a simplified way at the beginning of the building process, or it is done at the very end when all the needed information is available, but it is too late for decision-making. One reason for this is the lack of methods, workflows and tools to implement BIM-LCA integration over the entire building process. Therefore, the main objective of this study is to develop an integrated BIM-LCA workflow implemented into a method for the whole building process using an existing structure for cost estimation. A tool is created and used in a case study in Switzerland to test the developed approach. The results of this study show that LCA can be performed continuously in each building phase over the entire building process using existing BIM modelling techniques. The main benefit of this approach is that the re-work caused by the need for re-entering data and the usage of many different software tools that characterise most of the current LCA practices is minimised. Furthermore, decision-making, both at the element and building levels, is supported.

Members of the genus Mycoplasma and related organisms impose a substantial burden of infectious diseases on humans and animals, but the last comprehensive review of mycoplasmal pathogenicity was published 20 years ago. Post-genomic analyses have now begun to support the discovery and detailed molecular biological characterization of a number of specific mycoplasmal virulence factors. This review covers three categories of defined mycoplasmal virulence effectors: 1) specific macromolecules including the superantigen MAM, the ADP-ribosylating CARDS toxin, sialidase, cytotoxic nucleases, cell-activating diacylated lipopeptides, and phosphocholine-containing glycoglycerolipids; 2) the small molecule effectors hydrogen peroxide, hydrogen sulfide, and ammonia; and 3) several putative mycoplasmal orthologs of virulence effectors documented in other bacteria. Understanding such effectors and their mechanisms of action at the molecular level connects the biology of the bacteria to direct effects on the host and host responses they elicit, and is expected to translate into new interventions for human and veterinary mycoplasmosis.

Influenza A viruses (IAV) are widespread viruses affecting avian and mammalian species worldwide. Outbreaks of IAV in poultry are usually associated with substantial morbidity and mortality, significantly affecting the poultry industry and food security. IAVs from avian species can be transmitted to mammals including humans and, thus, they are of inherent pandemic concern. Most of the efforts to understand the pathogenicity and transmission of avian origin IAVs have been focused on H5 and H7 subtypes due to their highly pathogenic phenotype in poultry. However, IAV of the H9 subtype that circulate endemically in poultry flocks in some regions of the world have also been associated with cases of zoonotic infections. As a result, the World Health Organization includes avian origin H9N2 IAV among the top in the list of IAVs of pandemic concern. In this review, we discuss the interspecies transmission of H9N2 between avian and mammalian species and the molecular factors that are thought relevant for this spillover. Additionally, we discuss factors that have been associated with the ability of these viruses to transmit through the respiratory route in mammalian species.

Blackcurrant leaf chlorosis associated virus (BCLCaV) was detected recently by next-generation sequencing (NGS) and proposed as a new and distinct species in the genus Idaeovirus. Genomic components of BCLCaV that were detected and confirmed include: 1) RNA-1 that is monocistronic and encodes the replicase complex; 2) a bicistronic RNA-2 that encodes a movement protein (MP) and the coat protein (CP) of the virus, with open reading frames (ORF) that overlap by a single adenine (A) nucleotide (nt) representing the third position of an opal stop codon of the MP ORF2a and the first position of the start codon of the CP ORF2b; 3) a subgenomic form of RNA-2 (RNA-3) that contains ORF2b; and 4) a concatenated form of RNA-2 that consists of a complementary and inverted RNA-3 conjoined to the full-length RNA-2. Analysis of NGS-derived paired-end reads revealed the existence of bridge reads encompassing the 3’-terminus and 5’-terminus of RNA-2 or RNA-3 of BCLCaV. The full RNA-2 or RNA-3 could be amplified using outward facing or abutting primers; also RNA-2/RNA-3 could be detected even after three consecutive RNase R enzyme treatments with denaturation at 95 ^oC preceding each digestion. Evidence was obtained indicating that there are circular forms of BCLCaV RNA-2 and RNA-3.

Although RNA modifications were discovered decades ago, the identification of enzymes that write, read, and erase RNA modifications enabled their functional study and spawned the field of epitranscriptomics. Coupling that knowledge to new methods has enabled the precise pinpointing of epitranscriptomic modifications across the transcriptome plus the elucidation of their functional consequences. PCIF1 (Phosphorylated CTD Interacting Factor 1) was shown to add N6, 2’-O-dimethyladenosine (m⁶Am) marks at the first nucleotide after the 5’ N7-methylguanosine (m⁷G) cap. In this review, we discuss the epitranscriptomic regulation of mRNA in general, and focus on m⁷G cap-adjacent m⁶Am in particular. m⁶Am positions can now be distinguished from N6-methyladenosine (m⁶A) using new techniques leveraging PCIF1-knockout cells. Although m⁶Am modification sites can be detected precisely, conflicting data have been published regarding how cap-adjacent m⁶Am marks affect their host mRNA. Discrepancies in the data mean that the effects of cap-adjacent m⁶Am on mRNA stability, decapping, and translation continue to be debated. Finally, while PCIF1 is predominantly nuclear, a subset of results suggest a possible cytoplasmic role as well. Taken together, these contradictory results which employed different methodologies and cell lines means that further experiments are required to determine the ultimate biological function(s) of m⁷G cap-adjacent m⁶Am.

The green biomass of horticultural plants contains valuable secondary metabolites (SM) which can potentially be extracted and sold. When exposed to stress, plants accumulate higher amounts of these SMs, making the extraction and commercialization even more attractive. We evaluated the potential for accumulating of the flavones cynaroside and graveobioside A in leaves of two bell pepper cultivars (Mavras and Stayer) when exposed to salt stress (100 mM NaCl), UVA/B excitation (UVA 4-5 W/m²; UVB 10-14 W/m² for 3 hours per day) or a combination of both stressors. HPLC analyses proved the enhanced accumulation of both metabolites under stress conditions. Cynaroside accumulation is effectively triggered by high-UV stress, whereas graveobioside A contents increase under salt stress. Highest contents were observed in plants exposed to combined stress. Effects of stress on overall plant performance differed significantly between treatments, with least negative impact on aboveground biomass found for high-UV stressed plants. The usage of two non-destructive instruments (Dualex and Multiplex) allowed us to gain insights in ontogenetical effects at the leaf level and temporal development of SM contents over time. Indices provided by those devices correlate fairly with amounts detected via HPLC (Cynaroside: R2 = 0.46 – 0.66; Graveobioside A: R2 = 0.51 – 0.71). The concentrations of both metabolites tend to decrease at leaf level during the ontogenetical development even under stress conditions. High-UV stress is a promising tool for enriching plant leaves with valuable SM without major effects on plant biomass. All data is available online [1].

In the last few decades, a lot has been written on the use of sustainable agriculture to improve ecosystem services for resilience to climate change. However, no tangible and systematic evidence exists on how this would participate in alleviating impacts on vulnerable rural communities. This paper provides a narrative systematic review (SR) integrated with a bibliometric analysis and a concept network analysis to understand how, in a changing climate, sustainable agriculture builds the resilience of agro-systems. The search was set from the date of the first relevant article until the end of 2018. Results generated have demonstrated that: a. Only single practices and methods have been studied to assess impacts on single ecosystem services. b. Soil quality and health are considered a key indicator of sustainable agriculture. c. Albeit the assessed practices and methods have shown to improve the biodiversity of agro-systems, which makes them more resilient to extreme climate events, we are still far from reaching interdisciplinary and multi-dimensional agriculture which integrates all management aspects and generates a full range of ecosystem services. In conclusion, the study addressed the following recommendations for the scientific community and for decision-makers to orient future research strategies and efforts: a. Integration of all agro-systems services into sustainable management using an ecosystem-based approach on a life-cycle basis using Life Cycle Assessment (LCA) method; b. Improving the scientific understanding of traditional knowledge for higher synergies and for further integration; c. Unification of assessment methods and indicators for the quantification of impacts; d. Creation of a platform to share, monitor, screen, and approve assessments and evaluations of sustainable agriculture by region.

Acrylamide (AA), a molecule which potentially increases the risk of developing cancer, is easily formed in food rich in carbohydrates, such as biscuits, wafers and breakfast cereals, at temperatures above 120 °C. Thus, it is eminent the need to detect and quantify the AA content in processed foodstuffs, in order to delineate the limits and mitigation strategies. This work reports the development and validation of a high-resolution mass spectrometry-based methodology for identification and quantification of AA in specific food matrices of biscuits, by using LC-MSⁿ with electrospray ionization and Orbitrap as mass analyser. The developed analytical method showed good repeatability (RSD_r 11.1%) and 3.55 μg kg^-1 and 11.8 μg kg^-1 as limit of detection (LOD) and limit of quantification (LOQ), respectively. The choice of multiplexed targeted-SIM mode (t-SIM) for AA and AA-d3 isolated ions provided enhanced detection sensitivity, as demonstrated in this work. Results for AA concentration obtained vary between 323.7 and 2056.1 μg kg^-1. During baking an increase in AA concentration was observed, as well as between samples taken from different areas of the baking oven. Statistical processing of data was performed in order to compare the AA levels with several production parameters, such as time/cooking temperature, placement on the cooking conveyor belt, color and moisture for different biscuits. The composition of the raw materials was statistically the most correlated factor with the AA content when all samples are considered. The statistical treatment presented herein enables an important prediction of factors influencing AA formation in biscuits contributing for putting in place effective mitigation strategies.

1) Background: The objective was to evaluate the corrosion resistance of different commercially pure ultrafine-grained (UFG) titanium and its alloys with acid etched surface processed by equal-channel angular pressing (ECAP); 2) Methods: Coarse-grained and UFG titanium samples were investigated using polarization resistance technique. Surface characteristics of the native oxidized layer were evaluated by TEM and XRD. Electrochemical tests were under physiological electrolyte at a rate of 1 and 10 mV/s. Weight loss tests were performed after immersion into HCl solution for up to 3 years; 3) Results: UFG titanium was less susceptible to corrosion which was identified under lower rates and at higher polarization resistance than its coarse grain counterparts. Titanium Grade 2 and Grade 4 demonstrated similar corrosion susceptibility. Titanium Grade 5 revealed a thin and tightly adhered native oxide layer with adequate corrosion resistance; 4) Conclusions: ECAP process imposed a more compact and adhered oxidized layer. Surface etching techniques delivered a thicker native TiO₂ layer, being both grain refinement and surface etching techniques responsible for the improved corrosion resistance of Titanium samples under physiological environment after 3 years of observation.

The effect of reprocessing on the quasi-static uniaxial tensile behavior of two commercial polypropylene (PP) based composites is experimentally investigated and modeled. In particular, the studied materials consist of an unfilled high-impact PP and a talc-filled high-impact PP. These PP composites are subjected to repeated processing cycles including a grinding step and an extrusion step to simulate recycling at the laboratory level, the selected reprocessing numbers for this study being 0, 3, 6, 9 and 12. Because the repeated reprocessing leads to thermo-mechanical degradation by chain scission mechanisms, the tensile behavior of the two materials exhibits a continuous decrease of elastic modulus and failure strain with increasing number of reprocessing. A physically consistent three-dimensional constitutive model is used to predict the tensile response of non-recycled materials with strain rate dependence. For the recycled materials, the reprocessing effect is accounted by incorporating the reprocessing sensitive coefficient into the constitutive model for Young’s modulus, failure strain, softening and hardening equations. Our predictions of true stress - true strain curves for non-recycled and recycled 108MF97 and 7510 are in a good agreement with experimental data.

State-of-the-art dielectrophoretic (DEP) separation techniques provide unique properties to separate particles from a liquid or particles with different properties such as material, morphology or size from each other. However, such separators do not operate at throughput that is sufficient for a vast fraction of separation tasks. The reason for this limitation is that, in order to move particles by dielectrophoresis, high electric field gradients to drive the separation are required. Conventionally, those gradients are generated by electrode microstructures that limit the maximum channel size. Here, we investigate DEP filtration, a technique that uses open porous microstructures instead of microfluidic devices to easily increase the filter cross section and therefore also the processable throughput by several orders of magnitude. Previously, we already separated baker’s yeast by DEP filtration in open porous ceramic structures. Now, we give a more elaborate experimental study about DEP filtration in these open porous structures and separate model particles, that are an order of magnitude smaller (500 nm, polystyrene), from aqueous suspensions. Almost 100% separation at flow rates of up to 9 mL min^-1 was achieved while the majority of the trapped particles could be recovered. We show how particle separation depends on key parameters (voltage, throughput, filter structure size). Further, we work towards selective particle separation and show that particle separation is very dependent on the particle polarizability: This creates the possibility to adjust selectivity by changing the electrical conductivity of the suspension around that of the particle. This study highlights the unique qualities of dielectrophoretic filtration enabling switchable, selective, and scalable particle separation to solve existing problems such as cell separation or precious metal recovery.

The conversion of methane into chemicals is of interest to achieve a decarbonized future. Fuel cells are electrochemical devices commonly used to obtain electrical energy, but can be utilized either for chemicals production or both energy and chemicals cogeneration. In this work, the partial oxidation of methane in fuel cells for electricity generation and valuable chemicals production at the same time is reviewed. For this purpose, different types of methane-fed fuel cells, both low temperature fuel cells, such as PEMFCs and AAEMFCs, and high temperature fuel cells, such as SOFCs, have been used. Also if few works have been devoted to this topic, the promising results drive the development of fuel cells using methane as the source for the cogeneration of power and valuable chemicals.

Lipophilicity can be measured with different methods, such as Shake-Flask or liquid chromatography. HPLC presents the advantage of overcoming solubility issues and therefore extending the range of lipophilicity to high values. A specific HPLC method, called ELogD, had been developed 20 years ago on a C₁₆-amide stationary phase, enhancing hydrophobic and hydrogen bond interactions to mimic octanol-water partition. The emergence of novel stationary phases added to the need for a less complex mobile phase has led to the development of a new HPLC assay called alphaLogD, applicable to neutral and basic compounds at pH 7.4, that combines superficially porous particles, a high number of equilibriums between solutes and stationary phase, and results in a lower number of isocratic methods to determine the logk’_w at a higher throughput. Statistical studies have been run to successfully evaluate the alphaLogD method compared to the Shake-Flask method and to allow this lipophilicity measurement into the so-called Beyond-Rule-of-5-molecules space.

Recent results have shown that the human malaria-resistant hemoglobin S mutation originates de novo more frequently in the gene and in the population where it is of adaptive significance, namely, in the hemoglobin subunit beta gene compared to the non-resistant but otherwise identical 20A>T mutation in the hemoglobin subunit delta gene, and in sub-Saharan Africans, who have been subject to intense malarial pressure for many generations, compared to Northern Europeans, who have not. This finding raises a fundamental challenge to the traditional notion of accidental mutation. Here we address this finding with the replacement hypothesis, according to which pre-existing genetic interactions can lead directly and mechanistically to mutations that simplify and replace them. Thus, a gradual evolutionary process under selection can hone in on interactions of importance for the currently evolving adaptations, from which large-effect mutations follow that are relevant to these adaptations. We exemplify this hypothesis using multiple types of mutation, including gene fusion mutations, gene duplication mutations, A>G mutations in RNA-edited sites and transcription-associated mutations, and place it in the broader context of a system-level view of mutation origination called Interaction-based Evolution. Potential consequences include that similarity of mutation pressures may contribute to parallel evolution in genetically related species, that the evolution of genome organization may be driven by mutational mechanisms, that transposable element movements may also be explained by replacement, and that long-term directional mutational responses to specific environmental pressures are possible. Such responses need to be further tested by future studies in natural and artificial settings.

Ammonia produced using renewable hydrogen is being viewed as a promising media for the export of energy from locations rich in renewable energy sources. Solid oxide fuel cells (SOFCs) are efficient devices for converting such exported ammonia back into electricity at the point of use, however investigations on materials and operating regime for direct ammonia fuelled SOFCs are limited. The studies on fuel electrodes tailored specifically for ammonia fuel are limited. In this work, we evaluated the direct ammonia SOFC performance with Silver-Lanthanum Strontium Cobalt Ferrite (Ag-LSCF) composite anode and a novel Palladium (Pd) nanoparticle decorated Silver-Lanthanum Strontium Cobalt Ferrite (Pd-Ag-LSCF) composite anode in the temperature range of 500 °C to 800 °C. It is hypothesized that Palladium nanoparticles in the anode provide hydrogen dissolution and shift the ammonia decomposition reaction towards the right. The cell performance was evaluated with both hydrogen and ammonia as fuels and a clear-cut improvement in the performance was observed with the addition of Pd for both the fuels. The results showed a performance enhancement by 20% and 43% with hydrogen and ammonia fuels respectively from the Pd addition of Ag-LSCF anode. Open circuit voltage (OCV) values of the cells with hydrogen and ammonia fuel recorded over the temperature range of 500 °C to 800 °C indicated the possibility of direct electro-oxidation of ammonia in SOFCs.

Nowadays, all the stakeholders, policy makers, regulators, aircraft designers, producers, operators, etc.) are intensively working on development of the aircraft with full electric and hybrid propulsion systems. However, the technical, technological constrains (like limit on accumulator energy density) require introducing a new approach to conceptual design of such aircraft. The new methods is based on energy and mass balance evaluation. This paper analyses the identified constrains; integrates the energy and mass balance equations into the preliminary definition and calculations of the aircraft performance. By this way, the technological constrains might be transferred into the limitation on the aircraft energy and mass breakdown, that initiates a new approach to aircraft conceptual design uses the knowledge based multidisciplinary optimization. The paper describes the developed methodology for conceptual design of aircraft. It show results of implementing this new development philosophy to conceptual design of a four-seat small electric/hybrid aircraft and a special hybrid cargo UAV. The discussion of the results including got by using the emerging and enabling new technologies and new methods and solutions (including for example distributed propulsion system, unconventional forms, morphing, biomimics, etc.), demonstrates the possible implementation of the new development philosophy, new approach to aircraft conceptual design.

Food consumption in Europe is changing. Red meat consumption has been steadily decreasing in the past decades. The rising interest of consumers for healthier and more sustainable meat products provide red meat producers with the opportunity to differentiate their offers by ecolabels, origin and health claims. This international study analyses the European consumer preferences for red meat (beef, lamb and goat) in seven countries: Finland, France, Greece, Italy, Spain, Turkey and the United Kingdom. Through a choice experiment, 2.900 responses were collected. Mixed multinomial logit models were estimated to identify heterogeneous preferences among consumers at the country level. Results indicate substantial differences between the most relevant attributes for the average consumers, as well as their willingness to pay for them in each country. Nevertheless, national origin and organic labels were highly valued in most countries.

Every year, General Practitioners (GPs) see over 13 million patients for dermatological concerns making dermatology the highest referring speciality. Artificial Intelligence (AI) systems could improve system efficiency by supporting clinicians in making appropriate referrals, but they are, like human clinicians, imperfect and there may be a trade-off between sensitivity and specificity that is likely to result in false negatives. In this paper, a study is presented to explore two areas. Firstly, the aptitude of GPs to trust appropriately (or not trust) the outputs of a fictitious AI-based decision support tool when assessing skin lesions. Secondly, to identify which individual characteristics could make GPs less prone to adhere to erroneous diagnostics results and to refrain from passive adherence to AI. Findings suggest that when the AI is correct, there is a positive effect on GPs’ performance and confidence suggesting the potential to reduce referrals for benign lesions. However, when an inexperienced GP is presented with a false-negative result, they may passively deviate from their initial clinical judgement to accept the wrong diagnosis provided. AI systems will have a false-negative rate and, when adopting new technologies, this needs to be acknowledged and fed into risk-benefit discussions and considerations around additional safety measures.

Investments in public transit infrastructure in Latin America and the Caribbean often aim to reduce spatial and social inequalities by improving accessibility to jobs and other opportunities for vulnerable populations. The Metropolitano, Lima’s Bus Rapid Transit (BRT) project had as one of its central goals to connect low-income populations living in the peripheries to jobs in the city center. We examine the contribution of Lima’s BRT system to accessibility to employment in the city, particularly for low-income public transit users. Building on secondary datasets of employment, household socio-demographics and Origin-Destination surveys before and after the BRT began operations, we assess its effects on potential accessibility to employment, comparing impacts amongst lower versus higher income populations. Findings suggest that the BRT line reduced travel times to reach jobs, in comparison with traditional public transport in the city, amongst populations living within walking distance of the system. However, we also find that the coverage of the BRT declines in areas with high concentrations of poor and extreme poor populations, limiting the equitability of the accessibility improvements. We analyze the distributional effects of BRT infrastructure and services, discussing policy avenues that can improve the prospects for BRT system investments to include the poor in their mobility benefits.

Antigen-based rapid diagnostic tests for Lymphatic filariasis do not come with quality control (QC) materials, and research and disease control programmes rely on stored positive plasma samples. This study was undertaken to evaluate the use of freeze-dried Wuchereria bancrofti antigen positive plasma samples to serve as QC materials for LF RDTs. 10 well characterized W. bancrofti positive samples were lyophilized and stored at 4°C, 28°C and 40°C. The samples were evaluated using the Filaria Test Strips before lyophilization and after one and three (3) months of storage. The sensitivity and stability of the lyophilized samples were evaluated. The results revealed a loss of sensitivity and stability with increasing temperature and duration of storage. The results are further discussed in terms of the use of Dried Blood Spot (DBS) in diagnostics studies on LF requiring quantitative assessments, and the need for thoughtful DBS preparation and storage.

The manipulation of participant allocation in randomized controlled trials to achieve equal groups sizes may introduce allocation bias potentially leading to larger treatment effect estimates. This study aimed to estimate the proportion of nursing trials that have precisely equal group sizes and examine if there was an association with trial outcome. Data were extracted from a sample of 148 randomized controlled trials published in nursing science journals in 2017. One hundred trials (68%) had precisely equal group sizes. Respectively, a positive outcome was reported in 70% and 58% of trials with equal/unequal groups. Trials from Asia were more likely to have equal group sizes than those from the rest of the world. Most trials reported a sample size calculation (n=105, 71%). In a third of trials (n=36, 34%), the number of participants recruited precisely matched the requirement of the sample size calculation; this was significantly more common in studies with equal group sizes. The high number of nursing trials with equal groups may suggest nurses con-ducting clinical trials are manipulating participant allocation to ensure equal group size increasing the risk of bias.

Live attenuated influenza virus (LAIV) vaccines elicit a combination of systemic and mucosal immunity by mimicking a natural infection. To further enhance protective mucosal responses, we incorporated the gene encoding the IgA-inducing protein (IGIP) into the LAIV genomes of the cold-adapted A/Leningrad/134/17/57 (H2N2) strain (caLen) and the experimental attenuated backbone A/turkey/Ohio/313053/04 (H3N2) (OH/04att). Incorporation of IGIP into the caLen background led to a virus that grew poorly in prototypical substrates. In contrast, IGIP in the OH/04att background (IGIP-H1att) virus grew to titers comparable to the isogenic backbone H1att (H1N1) without IGIP. IGIP-H1att- and H1caLen-vaccinated mice were protected against lethal challenge with a homologous virus. The IGIP-H1att vaccine generated robust serum HAI responses in naïve mice against the homologous virus, equal or better than those obtained with the H1caLen vaccine. Analyses of IgG and IgA responses using a protein microarray revealed qualitative differences in humoral and mucosal responses between vaccine groups. Overall, serum and bronchoalveolar lavage samples from the IGIP-H1att group showed trends towards increased stimulation of IgG and IgA responses compared to H1caLen samples. In summary, introduction of genes encoding immunomodulatory functions into a candidate LAIV that can serve as natural adjuvants to improve overall vaccine safety and efficacy.

The forest transition – or forest-area transition – has been put forward as a land-use concept by A.S. Mather in 1992 (The forest transition. Area 24, 367-379), to describe the historical trend generally observed in the forest area of developed countries, embodied in a V-shaped curve of the forest area over time, and that may serve as a paradigm to understand and anticipate deforestation in the developing world. Well in line with a geographical approach to forests, forest transition has thus been defined as one-dimensional, forest area being the reference state variable. From a forestry perspective, the analysis appears to be reductive, as forests are described by many other state variables than area, including forest growing stock, composition in tree species, or stand structure. Whether the drivers of forest transition (population dynamics, economic modes of production and consciousness, as classified by Mather) also impact these other forest state variables in a general way thus comes forth as a logical issue.From a deductive analysis of forest transition drivers, and from forest trends brought to light in Europe, France, and at other places in the world, we here argue that the forest transition concept can be extended to a multi-dimensional space of forest attributes, characterized by typical ideal dynamics. Cumulative impacts onto forests and irreversible losses in forest biodiversity over a forest transition are hence highlighted. Global change, as a parallel consequence of countries’ developing process, further appears as one additional albeit less coupled dimension of forest transition, as it modifies forest productivity and vitality over time. Since forest ecosystem services and forest profitability primarily depend on such attributes, we argue that the extension of the forest transition concept has significance for land-use change and forest protection issues. A prospect on future changes in the forests of developed countries with the European space as a benchmark is finally proposed that leads to extend the temporal significance of forest transition. Though poorly described, returning forests on abandoned agricultural lands are significant, and deserve greater attention.

Over the course of the pandemic due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), multiple new clinical manifestations, as the consequence of the tropism of the virus, have been recognized. That includes now the neurological manifestations and conditions, such as headache, encephalitis, as well as olfactory and taste disorders. We present a series of ten cases of RT-PCR confirmed SARS-CoV-2 infected patients diagnosed with viral-associated olfactory and taste loss from four different countries.

The genetic aetiology of familial glioma is largely unknown. To gain further insight into the role of rare disruptive variants we performed whole exome sequencing (WES) of 17 glioma families, identifying two families where loss of function mutations in dynein axonemal heavy chain 11 (DNAH11) co-segregated with glioma (DNAH11 p.Ser1470ArgfsTer6 and p.Thr3900Lys) and single families implicating Telomere Replication Complex Component 1 (CTC1 p.Leu1058ProfsTer32) and filamin alpha (FLNA p.Ser1356Phe). We complemented linkage analysis by WES of 150 additional unrelated familial glioma cases and conducting gene burden tests leveraging WES data on 691 cases of glioma from TCGA. Our analysis does not provide support for a hitherto unidentified major cancer gene for glioma but highlights a series of novel candidate predisposition variants/genes, worthy of further investigation to shed light on glioma risk.

Background and Objective: Type 2 diabetes mellitus (DM2) and breast cancer (BC) are diseases of high prevalence worldwide. Both alter lung function separately. So suffering both tables would increase this decrease in lung function. The objetive was to determine the effects of DM2 and BC on ventilation volumes and pressures in adult women. Material and Methods: Forty-two women patients were recruited, of whom 40 were accepted under the exclusion criteria. They were divided into four groups: control group (CG), DM2, BC and DM2+BC. Body plethysmography was used to measure forced vital capacity, lung volumes, airway resistance and muscle pressures. Finally the normality of the data was determined using Student's t test or the Mann-Whitney U test; the threshold of significance was p<0.05. Results: No significant differences were observed in the anthropometric variables between the control group and the other groups. The ventilation flows showed no significant differences, while the lung volumes presented significant differences in the inspiratory capacity (IC) variables (p<0,002). Maximum inspiratory and expiratory pressures (MIP-MEP) also presented significant diminution (p<0,001; p<0,041, respectively). Conclusions: From the results obtained we can conclude that the combination of type 2 diabetes mellitus with breast cancer caused a diminution in ventilation volumes and pressures, specifically in IC, MIP and MEP.

Replacing carbon by hydrogen is a huge step towards reducing CO₂ emissions in the iron- and steel-making industry. The reduction of iron oxides using hydrogen plasma smelting reduction as an alternative to conventional steel-making routes has been studied at Montanuniversitaet Leoben, Austria. The aim of this work was to study the slag formation during the reduction process and the reduction behaviour of iron oxides. Furthermore, the reduction behaviour of iron ore during continuous feeding was assessed. Mixtures of iron ore and calcined lime with a basicity of 0, 0.8, 1.6, 2.3, and 2.9 were melted and reduced by hydrogen. The off-gas composition was measured during the operations to calculate the process parameters. The reduction parameters, namely the degree of reduction, degree of hydrogen utilisation, produced iron, and slag, are presented. The results of the batch-charged experiments showed that at the beginning of the reduction process, the degree of hydrogen utilisation was high, and then, it decreased over the operation time. In contrast, during the continuous-feeding experiment, the degree of hydrogen utilisation could be kept approximately constant. The highest degrees of reduction and hydrogen utilisation were obtained upon the application of a slag with a basicity of 2.3. The experiment showed that upon the continuous feeding of iron ore, the best conditions for the reduction process using hydrogen could be applied.

Daily thousands of people and goods move along Brazilian Federal highways. Traffic accidents are numerous on these highways and have a significant impact, whether on the economy or the health system. Identifying predictor variables, the probability of an event occurring and how to mitigate them are of paramount importance for the actions of the transit authorities that manage these roads. The main contribution of this study is the development of a predictive machine learning model which uses open data to shows graphically the critical points in the highways. This model is fully reproducible and can be applied to any region worldwide helping to minimize the number of accidents and to prevent deaths by automotive collisions. For this study, 43 variables were analyzed supporting the identification of the causes of accidents with fatal victims on the main highways in the south of Brazil. RoadLytics is proposed as a supervised machine learning model, using the Random Forest algorithm to analyze about 33 thousand occurrences between 2017 and 2020. An exploratory analysis of the data was carried out to support the modeling and to facilitate data visualization. In this sense, heat maps were developed to support the analysis and identification of potential risk areas. The results show that BR386 highway registers the highest number of fatal occurrences, regardless of the season. Additionally, concerning the weather conditions, the analysis shows that 52% of accidents occurred in favorable conditions, such as clear skies, victimizing 501 people. The driver’s lack of attention is the main reason for the accidents’ occurrences. Applying the developed model, an accuracy of 77% was achieved for the classification of fatal accidents.

Methanol is a natural ingredient with major occurrence in fruit spirits, such as apple, pear, plum or cherry spirits, but also in spirits made from coffee pulp. The compound is formed during fermentation and the following mash storage by enzymatic hydrolysis of naturally present pectins. Methanol is toxic above certain threshold levels and legal limits have been set in most jurisdictions. Therefore, the methanol content needs to be mitigated and its level must be controlled. This article will review the several factors that influence the methanol content including the pH value of the mash, the addition of various yeast and enzyme preparations, fermentation temperature, mash storage, and most importantly the raw material quality and hygiene. From all these mitigation possibilities, lowering the pH value and the use of cultured yeasts when mashing fruit substances is already common as best practice today. Also a controlled yeast fermentation at acidic pH facilitates not only reduced methanol formation, but ultimately also leads to quality benefits of the distillate. Special care has to be observed in the case of spirits made from coffee by-products which are prone to spoilage with very high methanol contents reported in past studies.

Niemann-Pick type C (NPC) disease is a childhood autosomal recessive inherited rare neuro-degenerative disease, characterized by the accumulation of cholesterol and glycosphingolipids, implicating the autophagy-lysosome system. Inhibition of soluble epoxide hydrolase (sEH), an enzyme that metabolizes epoxy fatty acids (EpFAs) to 1,2-diols, exerts beneficial effects in mod-ulating inflammation and autophagy, critical features of the NPC disease. This study aimed to evaluate the effects of UB-EV-52 a sEH inhibitor (sEHi) in the Npc mouse model by administering for 4 weeks (5 mg/kg/day). Behavioral and cognitive assays (open field test (OF), elevated plus maze (EPM), novel object recognition test (NORT) and object location test (OLT) demonstrated that treatment produced an improvement in short- and long-term memory as well as in spatial memory. Moreover, the treatment with UB-EV-52 increased body weight and the lifespan by 25% and re-duced gene expression of the inflammatory markers (i.e. Il-1β and Mcp1) and improved oxidative stress (OS) markers (iNOS and Hmox1) in the treated Npc mice group. Regarding the autophagic markers, we surprisingly found significantly reduced levels of the ratio LC3B-II/LC3B-I and a significant reduction of brain protein levels of lysosomal-associated membrane protein-1 (LAMP-1) in Npc mice treated group compared to non-treated. Lipid profile analysis showed a significant reduction in lipid storage in the liver and some slight changes in brain tissue in treated Npc mice compared to non-treated groups. Thus, Our results suggest that the pharmacological inhibition of sEH ameliorates most of NPC’s characteristic traits in mice, demonstrating that sEH can be considered a potential therapeutic target for this condition.

Mitochondrial malfunction is supposed to be involved in the etiology and pathology of major depressive disorder (MDD). Here, we aimed to identify and characterize the molecular pathomechanisms related to mitochondrial disfunction in adult human skin fibroblasts which were derived from MDD patients or non-depressive control subjects. We found that MDD fibroblasts showed significantly impaired mitochondrial functioning: basal and maximal respiration, spare respiratory capacity, non-mitochondrial respiration and ATP-related oxygen consumption was lower. Moreover, MDD fibroblasts harbor lower ATP levels and showed hyperpolarized mitochondrial membrane potential. To investigate cellular resilience, we challenged both groups of fibroblasts with hormonal (dexamethasone) or metabolic (galactose) stress for one week, and found that both stressors increased oxygen consumption but lowered ATP content in MDD as well as in non-depressive control fibroblasts. Interestingly, the bioenergetic differences between fibroblasts from MDD or non-depressed subjects, which were observed under non-treated conditions, could not be detected after stress. Our findings support the hypothesis that altered mitochondrial function causes a bioenergetic imbalance which is associated with the molecular pathophysiology of MDD. The observed alterations in OXPHOS and other mitochondria-related properties represent a basis for further investigations of pathophysiological mechanisms and might open new ways to gain insight into antidepressant signaling pathways.

The long-term laboratory aspects of the effects of COVID-19 on liver function are still not well understood. Therefore, this study aimed to evaluate the hepatic clinical-laboratory profile of patients with up to 20 months of long-term COVID-19. A total of 243 patients of both sexes aged 18 years or older hospitalised in the acute phase of COVID-19 were included in this study. Liver function analysis was performed. Changes were identified in the mean levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), gamma-glutamyl transferase (GGT), and ferritin. Inflammatory markers such as ferritin > 300 U/L were observed in the group that presented more changes in liver function markers (ALT, AST, and GGT). Age ≥ 60 years, male sex, AST > 25 U/L, and GGT ≥ 50 or 32 U/L were associated with ALT > 29 U/L. There was a correlation between ALT and AST, LDH, GGT, and ferritin. Our findings suggest that ALT and AST levels may be elevated in patients with long-term COVID, especially in those hospitalised in the acute phase. In addition, ALT > 29 U/L was associated with other markers of liver injury, such as LDH, GGT, and ferritin.

This paper presents technical solutions to increase Industry 4.0 maturity. Within the “5G-Enabled Manufacturing” project, a 5G network has been deployed at the shop floor to enable fast and scalable connectivity. This network was used to connect a grinding machine to a private cloud to enable visibility and transparency of the production data, which is the basis for Industry 4.0 and smart manufacturing. Results indicate a present lack of commercially available product independent solutions for interconnection and data transfer despite the availability of open standards and well-documented demonstrator projects. The solution is described and discussed regarding technical interoperability, focusing on the system layout, communication standards, and open systems. From the discussion, it is derived that manufacturing end-users are in need to expand and further internalize knowledge on future information and communication technologies to reduce their dependency on equipment and technology providers.

Inducible genetically defined mouse models of cancer uniquely facilitate the investigation of early events in cancer progression, however there are valid concerns about the ability of such models to faithfully recapitulate human disease. We developed an inducible mouse model of progressive lung adenocarcinoma (LuAd) that combines sporadic activation of oncogenic KRas^G12D with modest overexpression of c-MYC (KM model). Histological examination revealed a highly reproducible transition from adenoma to locally invasive adenocarcinoma within 6 weeks of oncogene activation. Laser-capture microdissection coupled with RNA-SEQ was employed to determine transcriptional changes associated with tumour progression. Upregulated genes were triaged for relevance to human LuAd using datasets from Oncomine and cBioportal. Selected genes were validated by RNAi screening in human lung cancer cell lines and examined for association with lung cancer patient overall survival using KMplot.com. Depletion of progression-associated genes resulted in pronounced viability and/or cell migration defects in human lung cancer cells. Progression-associated genes moreover exhibited strong associations with overall survival, specifically in human lung adenocarcinoma, but not in squamous cell carcinoma. The KM mouse model faithfully recapitulates key molecular events in human lung cancer and is a useful tool for mechanistic interrogation of LuAd progression.

Background: The gut microbiome plays a major role in chronic diseases, of which several are characterized by an altered composition and diversity of bacterial communities. Large-scale sequencing projects allowed characterizing the perturbations of these communities. However, translating these discoveries into clinical applications remains a challenges. To facilitate routine implementation of microbiome profiling in clinical settings, portable, real-time, and low-cost sequencing technologies are needed. Results: Here, we propose a computational and experimental protocol for whole genome quantitative metagenomics studies of human gut microbiome with Oxford Nanopore sequencing technology (ONT) that could be applied to other microbial ecosystems. We developed a bioinformatic protocol to analyse ONT sequences taxonomically and functionally and optimized pre-analytic protocols including stool collection and DNA extraction methods to maximize read length. This is a critical parameter for the sequence alignment and classification. Our protocol was evaluated using simulations of metagenomic communities which reflect naturally occuring compositional variations. Next, we validated both protocols using stool samples from a bariatric surgery cohort, sequenced with ONT, Illumina and SOLiD technologies. Results revealed similar diversity and microbial composition profiles. Conclusion: This protocol can be implemented in the clinical or research setting, bringing rapid personalized whole genome profiling of target microbiome species.

Dengue is the most prevalent arthropod-borne disease globally and affects approximately 2.5 billion people living in over 100 countries. The increasing geographic expansion of Aedes aegypti mosquitoes which transmit the virus has made dengue fever a global health concern. There are currently no approved antivirals available to treat dengue, and the only approved vaccine used in some countries is limited to seropositive patients. Treatment of dengue therefore remains largely supportive to date; hence research efforts are being intensified for the development of antivirals against dengue. The NS3 and NS5 nonstructural proteins have been the major targets for dengue antiviral development due to their indispensable enzymatic and biological functions in the viral replication process. NS5 is the largest and most conserved nonstructural protein encoded by flaviviruses including dengue. Its multifunctionality makes it an attractive target for antiviral development against dengue, but research efforts are hindered due to its limited structural characterization compared to the NS5 of other flaviviruses like the Zika virus. Increase in structural insights into the dengue NS5 protein will accelerate drug discovery efforts focused on NS5 as an antiviral target. In this review, we will give an overview of the current state of therapeutic development against dengue.

Well differentiated liposarcoma (WD-LPS) is a relatively rare tumour, with less than 50 cases occurring per year in the UK. These tumours are both chemotherapy and radiotherapy resistant and present a significant treatment challenge requiring radical surgery. Little is known of the molecular landscape of these tumours and no current targets for molecular therapy exist. We aimed to carry out a comprehensive molecular characterisation of WD-LPS via whole genome sequencing, RNA-sequencing and methylation array analysis. A recurrent mutation within exon1 of FOXD4L3 was observed (chr9:70,918,189A>T; c.322A>T; p. Lys108Ter). Recurrent mutations were also observed in Wnt signalling, immunity, DNA repair and hypoxia-associated genes. Recurrent amplification of HGMA2 was observed, although this was in fact part of a general amplification of the region around this gene. Recurrent gene fusions in HGMA2, SDHA, TSPAN31 and MDM2 were also observed as well as consistent rearrangements between chromosome 6 and chromosome 12. Our study has demonstrated a recurrent mutation within FOXD4L3, which shows evidence of interaction with the PAX pathway to promote tumorigenesis.

Plant pathogenic fungi are the largest group of disease-causing agents on crop plants and represent a persistent and significant threat to agriculture worldwide. Conventional approaches based on the use of pesticides raise social concern for the impact on the environment and human health and alternative control methods are urgently needed. The rapid improvement and extensive implementation of RNAi technology for various model and non-model organisms has provided the initial framework to adapt this post-transcriptional gene silencing technology for the management of fungal pathogens. In this review, we describe exogenous RNAi involved in plant pathogenic fungi and discuss small RNA production, formulation, and RNAi delivery methods. We explore some challenges with possible solutions. Furthermore, exogenous RNAi holds great potential for RNAi-mediated plant pathogenic fungal disease control.

The astacin protease Meprin β represents an emerging target for drug development due to its potential involvement in disorders such as acute and chronic kidney injury and fibrosis. Here, we elaborate on the structural basis of inhibition by a specific Meprin β inhibitor. Our analysis of the crystal structure suggests different binding modes of the inhibitor to the active site. This flexibility is caused, at least in part, by movement of the C-terminal region of the protease domain (CTD). The CTD movement narrows the active site cleft upon inhibitor binding. Compared with other astacin proteases, among those the highly homologous isoenzyme Meprin α, differences in the subsites account for the unique selectivity of the inhibitor. Although the inhibitor shows substantial flexibility in the orientation within the active site, the structural data as well as binding analyses including molecular dynamics simulations support a contribution of electrostatic interactions, presumably by arginine residues, to binding and specificity. Collectively, the results presented here and previously support an induced fit and substantial movement of the CTD upon ligand binding and, possibly, during catalysis. To the best of our knowledge, we here present the first structure of a Meprin β holoenzyme containing a zinc ion and a specific inhibitor bound to the active site. The structural data will guide rational drug design and the discovery of highly potent Meprin inhibitors.

The present study uses the 3 years of data from a vertically pointed profile Radar (VPPR) at the mountain site (Huancayo at 3.2 km msl; HYO) in Peru to investigate the precipitation characteristics/patterns including diurnal variation, bright band (BB) characteristics and vertical structure of rain (VSR). VPPR provides continuous 1­min profiles of radar reflectivity (Ze), rain rate (RR), liquid water content (LWC) and Doppler velocity. At the same time, field campaign data are used to investigate the role of the surface and atmospheric variables in generating the rainfall and organization of the cloud systems over HYO. The precipitation shows the bimodal distribution; frequent and higher RR during afternoon and nighttime. The BB height also shows a diurnal pattern and BB height is higher during the afternoon and nighttime compared; and follows the diurnal heating of the Andes. More than 70% BB height lies between ~4.3­4.7 km and only 20% BB has altitude higher than 5 km. The austral summer monsoon (December to March months) have higher intense vertical profiles (higher Z e ) compared to pre monsoon seasons (September to November) and shows the nega­tive gradient for most of the altitude. The RR and LWC show the opposite characteristics, and both have a positive gradient below the 6 km altitude and then negative gradient above 6 km altitude. The raindrop size distribution (DSD) parameters show most of the variation below the freezing level, and a higher concentra­tion of large sized of hydrometeors are observed for higher RR, however the dominant modes of Dm are less than 1 mm. The changes in the VSR in DSD parameters are significant for the RR>20 mm/h, whereas for RR<2 mm/h the vertical structure in DSD parameters do not have much differences during monsoon and premonsoon seasons. Satellite and reanalysis data reveal the short periods of convective activity with higher ac­ cumulated rainfall over HYO compared to stratiform precipitation, which is more common in the nighttime and sustain for many hours. Wet spells (higher rainy days) have low pressure circulation, which favours the transport of moisture from the Amazon to the central Sierra of Peru, while the anticyclonic circulation at high levels favours the divergence at higher pressure levels and, enhances the convective in the region. During the dry spells, low level weaker circulation at the west of Brazil, restricts the transport of moisture to the central Sierra, while the circulation at high levels does not favor rain processes. The improved understanding of the tropical Andes precipitation would be very important for assessing climate variability and changes as well as to forecast precipitation using the numerical models.

Impaired wound healing is a significant financial and medical burden. The synthesis and deposition of extracellular matrix (ECM) in a new wound is a dynamic process that is constantly changing and adapting to the biochemical and biomechanical signaling from the extracellular microenvironments of the wound. This drives either a regenerative or fibrotic and scar-forming healing outcome. Disruptions in ECM deposition, structure, and composition lead to impaired healing in diseased states, such as in diabetes. Valid measures of the principal determinants of successful ECM deposition include bacterial contamination, tissue perfusion, and mechanical injury and strain. These measures are used by wound-care providers to intervene upon the healing wound to steer healing toward a more functional phenotype with improved structural integrity and healing outcomes and to prevent adverse wound developments.In this review, we discuss bioengineering advances in non-invasive detection of biologic and physiologic factors of the healing wound, visualizing and modeling the ECM, and computational tools to efficiently evaluate the complex data acquired from the wounds to prognosticate healing outcomes and intervene effectively. We focus on bioelectronics and biologic interfaces of the sensors and actuators for real time biosensing and actuation. We also discuss high-resolution, advanced imaging techniques, which go beyond traditional confocal and fluorescence microscopy to visualize microscopic details of the composition of the matrix, linearity of collagen, and live tracking of components within the ECM. Computational modeling of the matrix, including partial differential equation datasets as well as machine learning models that can serve as powerful tools for physicians to guide their decision-making process are discussed.

Network coding approaches typically consider an unrestricted recoding of coded packets in the relay nodes for increased performance. However, this can expose the system to pollution attacks that cannot be detected during transmission, until the receivers attempt to recover the data. To prevent these attacks while allowing for the benefits of coding in mesh networks, the Cache Coding was proposed. This protocol only allows recoding at the relays when the relay has received enough packets to decode an entire generation of packets. At that point, the relay node recodes and signs the recoded packets with its own private key allowing for the system to detect and minimize the effect of pollution attacks and make relays accountable for changes on the data. This paper analyzes the delay performance of Cache Coding to understand the security-performance trade-off of this scheme. We introduce an analytical model for the case of two relays in an erasure channel relying on an Absorbing Markov Chain and a approximate model to estimate the performance in terms of the number of transmissions before successfully decoding at the receiver. We confirm our analysis using simulation results. We show that Cache Coding can overcome security issues of unrestricted recoding with only a moderate decrease in system performance.

One of the critical tools for early detection and subsequent evaluation of the incidence of lung diseases is chest radiography. At a time when the speed and reliability of results, especially for COVID-19 positive patients, is important, the development of applications that would facilitate the work of untrained staff involved in the evaluation is also crucial. Our model takes the form of a simple and intuitive application, into which you only need to upload X-rays: tens or hundreds at once. In just a few seconds, the physician will determine the patient's diagnosis, including the percentage accuracy of the estimate. While the original idea was a mere binary classifier that could tell if a patient was suffering from pneumonia or not, in this paper we present a model that distinguishes between a bacterial disease, a viral infection, or a finding caused by COVID-19. The aim of this research is to demonstrate whether pneumonia can be detected or even spatially localized using a uniform, supervised classification.

The Avian retina is far less known than that of mammals such as mouse and macaque, and detailed study is overdue. The chicken (Gallus gallus) has potential as a model, in part because research can build on developmental studies of the eye and nervous system. One can expect differences between bird and mammal retinas simply because whereas most mammals have three types of visual photoreceptor birds normally have six. Spectral pathways and colour vision are of particular interest, because filtering by oil droplets narrows cone spectral sensitivities and birds are probably tetrachromatic. The number of receptor inputs is reflected in the retinal circuitry. The chicken probably has four types of horizontal cell, there are at least 11 types of bipolar cell, often with bi- or tri-stratified axon terminals, and there is a high density of ganglion cells, which make complex connections in the inner plexiform layer. In addition, there is likely to be retinal specialisation, for example chicken photoreceptors and ganglion cells have separate peaks of cell density in the central and dorsal retina, which probably serve different types of behaviour.

As time progresses and technology improves, biological data sets are continuously increasing in size. New methods and new implementations of existing methods are needed to keep pace with this increase. In this paper, we present a high performance computing(HPC)-capable implementation of Iterative Random Forest (iRF). This new implementation enables the explainable-AI eQTL analysis of SNP sets with over a million SNPs. Using this implementation we also present a new method, iRF Leave One Out Prediction (iRF-LOOP), for the creation of Predictive Expression Networks on the order of 40,000 genes or more. We compare the new implementation of iRF with the previous R version and analyze its time to completion on two of the world's fastest supercomputers Summit and Titan. We also show iRF-LOOP's ability to capture biologically significant results when creating Predictive Expression Networks. This new implementation of iRF will enable the analysis of biological data sets at scales that were previously not possible.

Over the years, sustainability, impact on the environment, as well as the operation expenditure have been a major concern to the deployment of mobile cellular base stations worldwide. This is because the mobile cellular base stations are known to consume a high percentage of power within the mobile cellular network. Such energy consumption contributes to the emission of Greenhouse Gases (GHG) through the use of conventional diesel generating a set. As a result, the mobile cellular operators are faced with the dilemma of minimising the power consumption, GHG emission, and the operation cost, while improving the Quality of Service of the networks. In attempting to find a solution, this study presents the feasibility and simulation of a solar photovoltaic (PV) with battery hybrid power system (HPS) as a predominant source of power for a specific mobile cellular base station site situated in Soshanguve area of the city of Pretoria, South Africa. It also presents the technical development, showed the environmental advantage and cost benefits of using a solar PV-battery HPS to power a base station site of a 24 hrs daily load of 241.10 kWh/d and the peak load of 20.31 kW as compared to using the HPS of solar PV-diesel generating set-battery. The solar resource pattern for the city of Pretoria was collected from The National Aeronautics and Space Administration and modelled statistically. Thus, the statistical modelling done using solar radiation resource exposure characteristic patterns of Pretoria, South Africa, revealed an average annual daily solar radiation of 5.4645 Wh/m2/d and 0.605 clearness index. The simulation and the design were done using the Hybrid Optimization Model for Electric Renewables and Matlab/Simulink software. The simulation finding shows that the HPS of solar PV-battery combination has about 59.62 % saving on Net Present Cost, Levelized Cost of Energy, and 80.87% saving on Operating cost as against conventional BS powered with Gen Set-Battery.

Levan is a fructan-type exopolysaccharide, which is produced by many microbes from sucrose via extracellular levansucrases. The hydrocolloid properties of levan depend on its molecular weight, while it is unknown why and to which extent levan is functionally diverse in dependence of its size. The aim of our study was to get deeper insights into the size-dependent, functional variability of levan. For this purpose, levans of different sizes were produced using the water kefir isolate Gluconobacter albidus TMW 2.1191 and subsequently rheologically characterized. Three levan types could be identified, which are similarly branched, but significantly differ in their molecular size and rheological properties among each other. The smallest levan (< 107 Da) produced without adjustment of the pH exhibited Newton-like flow behavior up to a specific concentration of 25% (w/v). On the contrary, larger levans (> 108 Da) produced at pH ≥ 4.5 were shear-thinning and showed a gel like behavior at ≥ 5% (w/v). A third (intermediate) levan variant was obtained via production in buffers at pH 4.0 and exhibited the properties of a viscoelastic fluid at ≥ 5% (w/v). Our study reveals that the variable size and composition of levan are controllable and more decisive for its functionality than the amount of exerted levan.

Objective: The objective of the present study was to evaluate the activities of daily living using the Barthel Index, before and after the infection by SARS-COV-2 and to see if the results vary according to sex. Methods: The activities of daily living of 68 cohabiting geriatric patients, 34 men and 34 women, in 2 nursing homes were measured before and after SARS-COV-2 infection using the Barthel index. Results: The Covid 19 infection affects the performance of daily life activities in institutionalized elderly in nursing homes, and it does so especially the older the subject, regardless of sex. Conclusions: The Covid 19 pandemic, in addition to having claimed some victims, especially in the elderly population, has reduced the ability of these people to carry out their activities of daily life, considerably worsening their quality of life despite have been able to overcome the disease.

The present review provides an in-depth look into the complex topic of delimiting species in sea anemones. For most part of history this has been based on a small number of variable anatomic traits, many of which are used indistinctly across multiple taxonomic ranks. Early attempts to classify this group succeeded to comprise much of the diversity known to date, yet numerous taxa were mostly characterized by the lack of features rather than synapomorphies. Of the total number of species names within Actiniaria, about 77% are currently considered valid and more than half of them have several synonyms. Besides the nominal problem caused by large intraspecific variations and ambiguously described characters, genetic studies show that morphological convergences are also widespread among molecular phylogenies. On the contrary, spatial distribution has been emerging as a more reliable parameter to explain cryptic relationships among sea anemones. Integrative approaches and genome-wide data have been especially helpful to unveil the mechanisms behind the speciation process, which is typically marked by large genetic differences among populations, even from neighbouring localities. This paper further discusses current gaps in our knowledge and offers some future directions on how to address the issue of species delimitation in the extremely polymorphic group of sea anemones.

Serological human birth cohort studies have identified maternal infection during pregnancy as a risk factor for development of disorders such as Autism Spectrum Disorder and schizophrenia in offspring. Similarly, in experiments using animal models, maternal immune activation (MIA) has been shown to alter neuroanatomical and behavioral development in offspring. This study employs magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) in conjunction with behavioral assays to refine our understanding of the impact of MIA on neurobiological development in exposed animals. On gestational day nine, pregnant dams were injected with either polyinosinic:polycytidylic acid (POL) to induce MIA or saline (SAL) as a control. Whole-brain MRI, localized proton MRS, and behavioral tests (open field, three chambered social approach, and prepulse inhibition) were acquired at two timepoints, during adolescence (postnatal day [PND] 35) and adulthood (PND 60). Whole-brain voxel-wise volumetric analyses revealed that MIA offspring exhibited altered volume in the hippocampus and caudate putamen (CPu) between adolescence and early adulthood. MRS data were assessed at each timepoint separately; MIA offspring during early adulthood but not adolescence exhibited trending reductions in γ-aminobutyrate (GABA) (p = 0.06) and myo-inositol (Ins) (p = 0.08) compared to saline controls. However, these metabolite differences did not reach levels of significance, even before multiple comparison corrections. Open field testing revealed that during adolescence, MIA offspring displayed a more anxious phenotype than controls wherein they spent less time in the anxiogenic center zone of the open field arena (p < 0.007), but this difference normalized by adulthood. There were no significant differences in sociability preference, novelty preference, or prepulse inhibition comparing the groups. Results suggest that early gestational exposure to MIA results in subtle neuroanatomical changes in the trajectories of development, trending behavioral changes in adolescent offspring, and slight neurochemical changes in young adult offspring. Maternal infection alone may not be enough; additional genetic or environmental risk factors may be required to elicit the more typical symptoms of neuropsychiatric disorders.

It is well established the complex exponential and logarithm are multivalued functions, both failing to maintain most identities originally valid over the positive integers domain. Moreover the general case of complex logarithm, with a complex base, is hardly mentionned in mathematic litterature. We study the exponentiation and logarithm as binary operations where all operands are complex. In a redefined complex number system using an extension of the C field, hereafter named E, we prove both operations always produce single value results and maintain the validity of identities such as log_u (w v) = log_u (w) + log_u (v) where u, v, w in E. There is a cost as some algebraic properties of the addition and subtraction will be diminished, though remaining valid to a certain extent. In order to handle formulas in a C and E dual number system, we introduce the notion of set precision and set truncation. We show complex numbers as defined in C are insufficiently precise to grasp all subtleties of some complex operations, as a result multivaluation, identity failures and, in specific cases, wrong results are obtained when computing exclusively in C. A geometric representation of the new complex number system is proposed, in which the complex plane appears as an orthogonal projection, and where the complex logarithm and exponentiation can be simply represented. Finally we attempt an algebraic formalization of E.

Dendritic cells (DCs) are unique immune cells that can link innate and adaptive immune responses and Immunometabolism greatly impacts their phenotype. Rapamycin is a macrolide compound that has immunosuppressant functions and is used to prevent graft loss in kidney transplantation. The current study evaluated the therapeutic potential of ex-vivo Rapamycin treated DCs to protect kidneys in a mouse model of acute kidney injury (AKI). For the Rapamycin single (S) treatment (Rapa-S-DC), Veh-DCs were treated with Rapamycin (10 ng/ml) for 1 hour before LPS. In contrast, Rapamycin multiple (M) treatment (Rapa-M-DC) were exposed to 3 treatments over 7 days. Only multiple ex-vivo Rapamycin treatments of DCs induced a persistent reprogramming of mitochondrial metabolism. These DCs had 18-fold more mitochondria, had almost 4-fold higher oxygen consumption rates, and produced more ATP compared to Veh-DCs (Veh treated control DCs). Pathway analysis showed IL10 signaling as a major contributing pathway to the altered immunophenotype after Rapamycin treatment compared to vehicle with significantly lower cytokines Tnfa, Il1b, and Il6, while regulators of mitochondrial content Pgc1a, Tfam, and Ho1 remained elevated. Critically, adoptive transfer of Rapamycin treated DCs to WT recipients 24 hrs before bilateral kidney ischemia significantly protected the kidneys from injury with a significant 3-fold improvement in kidney function. Last, the infusion of DCs containing higher mitochondria numbers (treated ex-vivo with healthy isolated mitochondria (10 µg/ml) one day before) also partially protected the kidneys from IRI. These studies demonstrate that pre-emptive infusion of ex-vivo reprogrammed DCs that have higher mitochondria content has therapeutic capacity to induce an anti-inflammatory regulatory phenotype to protect kidneys from injury.

Cyclic STAT3 decoy (CS3D) is a second-generation, double-stranded oligodeoxynucleotide (ODN) that mimics a genomic response element for signal transducer and activator of transcription 3 (STAT3), an oncogenic transcription factor. CS3D competitively inhibits STAT3 binding to target gene promoters, resulting in decreased expression of proteins that promote cellular proliferation and survival. Previous studies have demonstrated antitumor activity of CS3D in preclinical models of solid tumors. However, prior to entering human clinical trials, the efficiency of generating the CS3D molecule and its stability in biological fluids should be determined. CS3D is synthesized as a single-stranded ODN and must have its free ends ligated to generate the final cyclic form. In this study, we report a ligation efficiency of nearly 95 percent. The ligated CS3D demonstrated a half-life of 7.9 hours in human serum, indicating adequate stability for intravenous delivery. These results provide requisite biochemical characterization of CS3D that will inform upcoming clinical trials.

The effective management of Fusarium wilt of bananas (FW) depends on the knowledge of the disease dynamics in time and space. The objectives of this work were: To estimate disease intensity and impact, and to investigate the spatial and temporal dynamic of FW. Fields planted with Silk (n = 10), Pome (n = 17) or Cavendish (n = 3) banana subgroups were surveyed in Brazil, totaling 95 ha. In each field, all plants were visually assessed and diseased plants were georeferenced. The incidence of FW and the impact of the disease on yield on a regional scale were estimated. Spatial patterns were analyzed using quadrat- and distance-based methods. FW incidence ranged from 0.09 to 41.42%, being higher in Silk fields (median = 14.26%). Impacts of epidemics on yield ranged from 18.4 to 8,192.5 kg.ha-1.year-1, with a median of 935.2 kg.ha-1.year-1. The higher economic impact of the disease was observed on Silk cultivar with a median loss of US$ 910.5 ha-1.year-1. Overall, estimated losses increased on average by US$ 109.8 ha-1.year-1 at each 1% of incidence. Aggregation of FW was detected by all analytical methods in 13 fields (1 of Cavendish, 11 of Pome and 1 of Silk). In the other 17 fields, at least one analytical method did not reject the null hypothesis of randomness. One field (5 ha), composed of six plots, was selected for spatial and temporal studies during two years with bi-monthly assessments. A sigmoidal curve represented the FW progress and the Gompertz model best fitted disease progress. The level of aggregation varied over time, and evidence of secondary infection to neighboring and distant plants were detected. FW is a widespread problem in Brazil and yield losses can be of high magnitude. Epidemiology-based management strategies can now be better established.

The Human Gut Microbiome is an important host’s component defining its health. These microorganisms are mutualistic symbionts dependent on factors such as host’s age, subsistence models and sociocultural practices, among others. The conjunction of these factors define the microbial ecosystem dynamics. Using a fecal microbiome approach in children, a comparison of two Mexican communities with contrasting lifestyles: “westernized” (Mexico City) and “non-westernized” (Me’phaa indigenous group) was evaluated. The main differences between these two communities are in bacteria associated with different types of diets (high animal protein and refined sugars vs high fiber food, respectively). In addition, the gut microbiome of Me’phaa children showed higher total diversity and the presence of exclusive phyla, such as Deinococcus-Thermus, Chloroflexi, Elusimicrobia, Acidobacteria and Fibrobacteres. In contrast, Mexico City children had less diversity and the exclusive presence of Saccharibacteria phylum which is associated with the degradation of sugar compounds. This comparison allows further exploration of the selective pressures affecting microbial ecosystemic composition over the course of human evolution and the potential consequences of pathophysiological states correlated with westernization lifestyles.

The spreading global sea turtle fibropapillomatosis (FP) epizootic is threatening some of Earth’s ancient reptiles, adding to the plethora of threats faced by these keystone species. Understanding this neoplastic disease, and its likely aetiological pathogen, chelonid alphaherpesvirus 5 (ChHV5), is crucial to understand how the disease impacts sea turtle populations and species and the future trajectory of disease incidence. We generated 20 ChHV5 genomes, from three sea turtle species, to better understand the viral variant diversity and gene evolution of this oncogenic virus. We revealed previously underappreciated genetic diversity within this virus (with an average of 2,035 single nucleotide polymorphisms [SNPs], 1.54% of the ChHV5 genome) and identified genes under the strongest evolutionary pressure. Furthermore, we investigated the phylogeny of ChHV5 at both genome and gene level, confirming the propensity of the virus to be interspecific with related variants able to infect multiple sea turtle species. Finally, we revealed unexpected intra-host diversity, with up to 0.15% of the viral genome varying between ChHV5 genomes isolated from different tumours concurrently arising within the same individual. These findings offer important insights into ChHV5 biology and provide genomic resources for this oncogenic virus.

Fatty acids and glucose are the main bioenergetic substrates in mammals that are alternatively used during the transition between fasting and feeding. Impairment of mitochondrial fatty acid oxidation causes mitochondrial myopathy leading to decreased physical performance. Here, we report that haploinsufficiency of ADCK2, a member of the aarF domain-containing mitochondrial protein kinase family, in human is associated with liver dysfunction and severe mitochondrial myopathy with lipid droplets in skeletal muscle. In order to better understand the etiology of this rare disorder, we generated a heterozygous Adck2 knockout mouse model to perform in vivo and cellular studies using integrated analysis of physiological and omics data (transcriptomics-metabolomics). The data show that Aldh2+/- mice exhibits impaired fatty acid oxidation, liver dysfunction, and mitochondrial myopathy in skeletal muscle resulting in lower physical performance. Significant decrease in CoQ biosynthesis was observed and supplementation with CoQ partially rescued the phenotype both in the human subject and mouse model. These results indicate that ADCK2 is involved in organismal fatty acid metabolism and in CoQ biosynthesis in skeletal muscle. We propose that patients with isolated myopathies and myopathies involving lipid accumulation be tested for possible ADCK2 defect as they are likely to be responsive to CoQ supplementation.

Framed experiments and games are a useful medium to understand how context affects individual and group decision-making. They are particularly relevant for field research in agriculture, where alternative experimental designs can be costly and unfeasible. After a systematic review of the literature, we found that the volume of published studies employing coordination and cooperation games increased during the 2000-2020 period. In recent years, there has been greater attention given to natural resource management, conservation, and ecology areas, especially in strategic regions for agriculture sustainability. Other games, such as trust and risk games, have come to be regarded as standards of framed field experiments in agriculture. Regardless of sectoral focus, most games' results are subject to internal and external validity criticism. In particular, a significant portion of the games showed potential recruitment biases against women and no opportunities for a continued impact assessment. However, games' validity should be judged on a case-by-case basis. Specific cultural aspects of games might reflect the real context, and generalizing games' conclusions to different settings is often constrained by cost and utility. Overall, games in agriculture could benefit from more significant, frequent, and inclusive experiments and data – all possibilities offered by digital technology. Present-day physical distance restrictions may accelerate this shift. New technologies and engaging ways to approach farmers might represent a turning point for games in agriculture in the 21st century.

Mechanical robustness, biocompatibility, and antibacterial performances are key features for materials suitable to be used in tissue engineering applications. In this work, we investigated the link existing between structural and functional properties of TiCu(Ag) thin films deposited by physical vapor deposition magnetron sputtering on Si substrates. The thin films were characterized by X-ray diffraction (XRD), nanoindentation, atomic force microscopy (AFM), and X-ray photoelectron spectroscopy (XPS). The TiCu(Ag) thin films showed complete amorphous structure and improved mechanical properties in comparison with pure Ti films. However, for contents in excess of 20% Ag, we observed the appearance of nanometric Ag crystallite. The TiCu(Ag) thin films displayed excellent biocompatibility properties, allowing adhesion and proliferation of the human fibroblasts MRC-5 cell line. Moreover, all the investigated TiCu(Ag) alloy display bactericidal properties, preventing the growth of both Pseudomonas aeruginosa and Staphylococcus aureus. Results obtained from biological tests have been correlated to the surface structure and microstructure of films. The excellent biocompatibility and bactericidal properties of these multifunctional thin films opens to their use in tissue engineering applications.

Growing resistance is reported to carbamate insecticides in malaria vectors in Cameroon. However, the contribution of acetylcholinesterase (Ace-1) to this resistance remains uncharacterised. Here, we established that the G119S mutation is driving resistance to carbamates in Anopheles gambiae populations from Cameroon. Insecticide bioassay on field collected mosquitoes from Bankeng, a locality in southern Cameroon, showed high resistance to the carbamates bendiocarb (64.8 ± 3.5 % mortality) and propoxur (55.71 ± 2.9 %) but a full susceptibility to the organophosphate fenithrothion. The TaqMan genotyping of the G119S mutation in field-collected adults revealed the presence of this resistance allele (39%). A significant correlation was observed between the Ace-1^R and carbamate resistance at allelic [(bendiocarb; OR = 75.9; P<0.0001) and (propoxur; OR= 1514; P<0.0001)] and genotypic [RR vs SS (bendiocarb; OR = 120.8; P<0.0001) and (propoxur; OR= 3277; P<0.0001) levels. Furthermore, the presence of the mutation was confirmed by sequencing an Ace-1 portion flanking codon 119. The cloning of this fragment revealed a likely duplication of Ace-1 in Cameroon as mosquitoes exhibited at least three distinct haplotypes. Phylogenetic analyses showed that the predominant Ace-1^R allele is identical to that from West Africa suggesting a recent introduction of this allele in Central Africa from the West. The spread of this Ace-1^R represents a serious challenge to future implementation of IRS-based interventions using carbamates or organophosphates in Cameroon

The Sustainable Development Goals (SDGs) is a global strategy that aims to obtain a more equitable and just world. These objectives are organized in 17 SDGs, which are detailed in 169 targets. Different international institutions have emphasized education's relevance to developing citizens who contribute to the SDGs' achievement for 2030. However, a review focused on Physical Education exclusively has not been performed yet. Therefore, the objective of this work is double. First, to analyze and select the specific goals of the SDGs that can be implemented in the subject of Physical Education. And second, to relate these specific goals to the different models based on Physical Education practices. This review showed how three institutional documents have previously related sport, physical exercise and physical education to the specific goals of the SDGs. Based on the search done, this document selects those goals that could be integrated into the educational context through Physical Education. The bibliographic and narrative analysis carried out in this research shows that of the 169 specific goals proposed in the SDGs, only 24 could be worked on in Physical Education. In addition, after this previous analysis, a proposal for the relationship between the practice-based models and these 24 goals is presented. The contributions made in this paper will allow teachers to establish links between PE sessions and SDGs while raising awareness to develop students who contribute to a more sustainable world.

Phylogenetic and phylogeographic assessments of species should ideally include individuals of all known populations. However, this is difficult for species with large distribution areas. Previous molecular studies of the wide-ranging Eurasian lynx Lynx lynx focused mainly on its northern Palearctic populations, with the consequence that the reconstruction of this species’ evolutionary history did not include genetic variation present in its southern Palearctic distribution. We sampled a previously not considered Asian subspecies (L. l. dinniki), added published data from another Asian subspecies (L. l. isabellinus), and reassessed the Eurasian lynx mtDNA phylogeny along with previously published data from northern Palearctic populations. Our mitogenome-based analyses revealed that the subspecies L. l. isabellinus harbours the most basal matriline, consistent with the origin of Lynx lynx in this subspecies’ current range. L. l. dinniki harbours the second-most basal matriline, which is related to, and may be the source of, the mtDNA diversity of the critically endangered Balkan lynx L. l. balcanicus. Our results suggest that the Anatolian peninsula was a glacial refugium for Eurasian lynx, with previously unconsidered implications for the colonization of Europe by this species. Genetic variation present in southern Palearctic populations of Lynx lynx is clearly important for elucidating the evolutionary history of this species.

The catalytic decomposition of methane (CDM) process produces hydrogen in a single stage and avoids the CO₂ emission thanks to the formation of high added value carbon nanofilaments as by-product. In this work, Ni monometallic and Ni-Co, Ni-Cu and Ni-Fe bimetallic catalysts are tested in the CDM reaction for the obtention of fishbone carbon nanofibers (CNF). Catalysts, in which Al₂O₃ is used as textural promoter in their formulation, are based on Ni as main active phase for the carbon formation and on Co, Cu or Fe as dopants in order to obtain alloys with an improved catalytic behaviour. Characterization of bimetallic catalysts showed the formation of particles of Ni alloys with a bimodal size distribution. For the doping content studied (5 mol. %), only Cu formed an alloy with a lattice constant high enough to be able to favor the carbon diffusion through the catalytic particle against surface diffusion, resulting in higher carbon formations, longer activity times and activity at 750 °C, where Ni, Ni-Co and Ni-Fe catalysts were inactive. On the other hand, Fe also improved the undoped catalyst performance presenting a higher carbon formation at 700 °C and the obtention of narrow carbon nanofilaments from active Ni₃Fe crystallites.