Coronavirus is now a significant human pathogen with the emergence of SARS-CoV-2. Until now there has been no data to support a threat to agricultural industries. Using a comparative genomic protein analysis, this study examined the angiotensin-converting enzyme II (ACEII) gene of 17 animal species with an emphasis on agriculture. To determine viral vulnerability the 20 known SARS-CoV-2 receptor-binding domain (RBD)/ACEII receptor interaction sites were compared to determine their potential susceptibility to the SARS-CoV-2 virus. With the known bat host’s (XP_032963186) number of binding sites as a threshold, we note that ALL animal species examined in this study contained significant numbers (≥10) of SARS-CoV-2 binding sites and could be at risk for SARS-CoV-2 infection. The data from this study suggest SARS-CoV-2 imposes a grave threat to the safety and security of the agricultural industry. Urgent studies are needed to determine if infected animals can transmit SARS-CoV-2 before and/or after processing.

Background and motivation: Combining Deep Reinforcement Learning (Deep RL) and Health Systems Simulations has significant potential, for both research into improving Deep RL performance and safety, and in operational practice. While individual toolkits exist for Deep RL and Health Systems Simulations, no framework to integrate the two has been established. Aim: Provide a framework for integrating Deep RL Networks with Health System Simulations, and to ensure this framework is compatible with Deep RL agents that have been developed and tested using OpenAI Gym. Methods: We developed our framework based on the OpenAI Gym framework, and demonstrate its use on a simple hospital bed capacity model. We built the Deep RL agents using PyTorch, and the Hospital Simulation using SimPy. Results: We demonstrate example models using a Double Deep Q Network or a Duelling Double Deep Q Network as the Deep RL agent. Conclusion: SimPy may be used to create Health System Simulations that are compatible with agents developed and tested on OpenAI Gym environments. GitHub repository of code: https://github.com/MichaelAllen1966/learninghospital

In the last three decades, the robust scientific data emerged, demonstrating that the immune-inflammatory response is a fundamental component of the pathophysiology of major depressive disorder (MDD). Psychological stress and various inflammatory comorbidities contribute to such immune activation. Still, this is not uncommon that patients with depression do not have defined inflammatory comorbidities, and alternative mechanisms of immune activation need to take place. The gastrointestinal (GI) tract, along with gut-associated lymphoid tissue (GALT), constitutes the largest lymphatic organ in the human body and forms the biggest surface of contact with the external environment. It is also the most significant source of bacterial and food-derived antigenic material. There is a broad range of reciprocal interactions between the GI tract, intestinal microbiota, increased intestinal permeability, activation of immune-inflammatory response, and the CNS that has crucial implications in brain function and mental health. This intercommunication takes place within the microbiota-gut-immune-glia (MGIG) axis, and glial cells are the main orchestrator of this communication. A broad range of factors, including psychological stress, inflammation, dysbiosis and other, may compromise the permeability of this barrier. This leads to excessive bacterial translocation and the excessive influx of food-derived antigenic material that contributes to activation of the immune-inflammatory response and depressive psychopathology. This chapter summarizes the role of increased intestinal permeability in MDD and mechanisms of how the "leaky gut" may contribute to immune-inflammatory response in this disorder.

We have an unprecedented ability to map the Earth’s surface as deep learning technologies are applied to an abundance of high-frequency Earth observation data. Simple, free, and effective methods are needed to enable a variety of stakeholders to use these tools to improve scientific knowledge and decision making. Here we present a trained U-Net model that can map and delineate ground mounted solar arrays using publicly available Sentinel-2 imagery, and that requires minimal data pre-processing and no feature engineering. By using label overloading and image augmentation during training, the model is robust to temporal and spatial variation in imagery. The trained model achieved a precision and recall of 91.5% each and an intersection over union of 84.3% on independent validation data from two distinct geographies. This generalizability in space and time makes the model useful for repeatedly mapping solar arrays. We use this model to delineate all ground mounted solar arrays in North Carolina and the Chesapeake Bay watershed to illustrate how these methods can be used to quickly and easily produce accurate maps of solar infrastructure.

Alzheimer's disease (AD) has been the subject of extensive investigation as to its biological underpinnings. However, this has produced little of therapeutic benefit or indeed provided any accepted biomarkers that could tailor treatment. This chapter reviews data on the main pathophysiologic processes that have been widely shown to be altered in AD, including circadian dysregulation, mitochondrial dysfunction, gut dysbiosis, and immune-glia-platelet activation. It is proposed that alterations in the gut microbiome, including gut dysbiosis and increased gut permeability drive changes in mitochondrial function that are intimately associated with significant variations in sirtuin expression. Both mitochondria-located and nucleus/cytoplasm located sirtuins can act on mitochondrial function in different cells and body systems to co-ordinate the ageing-associated changes that underpin AD. The sirtuins are therefore key aspect to a developmental model of AD that is more 'holistic' in perspective, thereby providing a framework for the detection of earlier biomarkers and more successful treatment for the heterogenous nature of AD pathoetiology.

There is robust evidence that major depression (MDD) is accompanied by a low-grade activation of the immune-inflammatory response system, which is involved in the pathophysiology of this disorder. It is also becoming apparent that glia cells are in reciprocal communication with neurons and orchestrate various neuromodulatory, homeostatic, metabolic, and immune mechanisms and have a crucial role in neuroinflammatory mechanisms in MDD. Those cells mediate the central nervous system (CNS) response to systemic inflammation and psychological stress, but at the same time, they may be an origin of the inflammatory response in the CNS. The sources of activation of the inflammatory response in MDD are immense, however, in recent years, it is becoming increasingly evident that the gastrointestinal tract with gut-associated lymphoid tissue (GALT) and increased intestinal permeability to bacterial LPS and food-derived antigens contribute to activation of low-grade inflammatory response with subsequent psychiatric manifestations. Furthermore, an excessive permeability to gut-derived antigenic material may lead to subsequent autoimmunities which are also known to be comorbid with MDD. In this chapter, we discuss fascinating interactions between the gastrointestinal tract, increased intestinal permeability, intestinal microbiota, and glia-neuron crosstalk, and their roles in the pathogenesis of the inflammatory hypothesis of MDD. To emphasize those crucial intercommunications for the brain functions, we propose the term of microbiota-gut-immune-glia (MGIG) axis.

The progesterone receptor (PR) mediates progesterone regulation of female reproductive physiology, as well as gene transcription in non-reproductive tissues, such as brain, bone, lung and vasculature, in both women and men. An unusual property of progesterone is its high affinity for the mineralocorticoid receptor (MR), which regulates electrolyte transport in the kidney in humans and other terrestrial vertebrates. In humans, rats, alligators and frogs, progesterone antagonizes activation of the MR by aldosterone, the physiological mineralocorticoid in terrestrial vertebrates. In contrast, in elephant shark, ray-finned fishes and chickens, progesterone activates the MR. Interestingly, cartilaginous fishes and ray-finned fishes do not synthesize aldosterone, raising the question of which steroid(s) activate the MR in cartilaginous fishes and ray-finned fishes. The simpler synthesis of progesterone, compared to cortisol and other corticosteroids, makes progesterone a candidate physiological activator of the MR in elephant sharks and ray-finned fishes. Elephant shark and ray-finned fish MRs are expressed in diverse tissues, including heart, brain and lung, as well as, ovary and testis, two reproductive tissues that are targets for progesterone, which together suggests a multi-faceted physiological role for progesterone activation of the MR in elephant shark and ray-finned fish. The functional consequences of progesterone as an antagonist of some terrestrial vertebrate MRs and as an agonist of fish and chicken MRs are not fully understood. Indeed, little is known of physiological activities of progesterone via any vertebrate MR.

Knowledge of a lasers beam’s profile throughout a laser system and experiment can help immensely in diagnosing laser problems and assisting in beam alignment and focusing at a sample. Obtaining such profiles is a trivial task in the ultraviolet-visible wavelength range but more challenging with near-infrared to infrared beams. Scientific grade bolometer arrays, suitable for such a task, do exist but are extremely costly, relatively large and have a large pixel size, of the order of 80 μm, which is adequate for profiling larger beams but poses an issue when trying to profile sub 100 μm beams for example at a focal point. This communication identifies a micro-bolometer array for near- to mid-infrared laser beam profiling, which is extremely low cost. In addition, the device is very compact, enabling use in confined spaces, and has a small, 12 μm, pixel size permitting the profiling of focused laser beams. The best scientific grade device identified has a pixel size of 17 μm. This device is a powerful tool for infrared laser spectroscopists, reducing the time required to measure the spot size of beams and to achieve spatial overlap of multiple infrared beams as used in two-dimensional infrared spectroscopy, saving many hours of setup time. The use of the bolometer array as a spectrographic detector and probe of long-term beam drifts is also demonstrated.

Premenstrual syndrome (PMS) frequently occurs in women of childbearing age. There are different case definitions of PMS, one proposed by the American College of Obstetricians and Gynecologists (ACOG) and another based on the Daily Record of Severity of Problems (DRSP) scores. Here we review our recent papers indicating that the discovery of biomarkers of menstrual cycle-related symptoms is strongly dependent on the case definitions used and that the gold standard methods used to asses PMS, including the ACOG case definition, induce a high degree of false-negative findings. We propose a new case definition of the menstrual cycle-associated syndrome (MCAS), which is characterized by increased DRSP scores during the menstrual cycle and additionally by an exaggerated increase in symptoms the week prior to the menses. This case definition performed well and was externally validated by diverse biomarkers including plasma levels of progesterone and estradiol, chemokines (e.g. CCL2, CCL5 and CCL11), epidermal growth factor, hydroperoxides, paraoxonase 1 activity and complement C4. In conclusion, when evaluating menstrual cycle-related symptoms and their associations with biomarkers, we propose to assess daily measurements of the DRSP and based on those scores to a) use the diagnosis of MCAS as an indicant of menstrual cycle-related symptoms; and b) examine the associations of the time series in the DRSP and its subdomains (e.g. depression, physio-somatic, anxiety) and those in biomarkers including distributed lag models.

Ongoing debates regarding the virtues and challenges of implementing open science for brain imaging research mirror those of the larger scientific community. The present commentary acknowledges the merits of arguments on both sides, as well as the underlying realities that have forced so many to feel the need to resist the implementation of an ideal. Potential sources of top-down reform are discussed, along with the factors that threaten to slow their progress. The potential roles of generational change and the individual are discussed, and a starter list of actionable steps that any researcher can take, big or small, is provided.

Using analytic approach we study the effect of HPA axis secretions to the emotional variation of bipolar II disorder patient. Modified Duffing – Van der Pol oscillator was used to model the emotional variation, that was solved analytically using multiple scale perturbation to obtain an asymptotic solution. The solution was graphed to understand the effect of the variation of the cortisol to the oscillator. It was observed that the increase or decrease of the HPA hormone from the basal level in the body system, affects the mood variation of bipolar II disorder patients.

Urban cycling is a sustainable transport mode that cities currently try to expand. However, cities still do not take advantage of geospatial technologies to understand cycling mobility based on the behavioural patterns and difficulties faced by cyclists. This study analyses a geospatial dataset crowdsourced by urban cyclists using an experimental geo-game. About 20 participants per city recorded bicycle trips during one week and, by aggregating them, we found not only the cyclists’ preferred streets but also the frictions faced during cycling. We successfully identified 284 places potentially having frictions: 71 in Münster, Germany; 70 in Castelló, Spain; and 143 in Valletta, Malta. At such places, Participants not only recorded bicycle trips but also segments at lower speeds indicating a deviation from an ideal cycling scenario. We described the potential frictions preventing from bicycle commuting based on the distance to bicycle paths, surrounding infrastructure, and location in the urban area.

Inexpensive piezoelectric diaphragms can be used as sensors to facilitate both nozzle height setting and build platform leveling in FFF (Fused Filament Fabrication) 3D printers. Tests simulating nozzle contact are conducted to establish the available output and an output of greater than 8 Volts found at 20 ºC, a value which is readily detectable by simple electronic circuits. Tests are also conducted at a temperature of 80 ºC and, despite a reduction of greater than 80% in output voltage, this is still detectable. The reliability of piezoelectric diaphragms is investigated by mechanically stressing samples over 100,000 cycles at both 20 ºC and 80 ºC and little loss of output over the test duration is found. The development of a nozzle contact sensor using a single piezoelectric diaphragm is described.

The increasing popularity of porphyrins and hydroporphyrins for application in a variety of biomedical (photodynamic therapy, fluorescence tagging and imaging, photoacoustic imaging) and technical (chemosensing, catalysis, light harvesting) applications is also associated with the growing number of methodologies that enable their solubilization in aqueous media. Natively, the vast majority of synthetic porphyrinic compounds are not water-soluble. Moreover, any water-solubility imposes several restrictions on the synthetic chemist on when to install solubilizing groups in the synthetic sequence, and how to isolate and purify these compounds. This review summarizes the chemical modifications to render synthetic porphyrins water-soluble, with a focus on the work since 2000. Where available, practical data such as solubility, indicators for the degree of aggregation, and special notes for the practicioner are listed. We hope that this review will guide synthetic chemists through the many strategies known to make porphyrins and hydroporphyrins water soluble.

The potential of the Additive Manufacturing technologies is impeded by the surface finish obtained on the as-manufactured material. Therefore, the influence of various surface treatments, commonly applied to space hardware, on the mechanical properties of three selected metallic alloys (SS316L, AlSi10Mg, Ti6Al4V) prepared by using Selective Laser Melting (SLM) and Electron Beam Melting (EBM) additive manufacturing processes have been investigated. Within this study, SLM using EOS M400 and EOS M280 equipment and in addition EBM using an ARCAM Q20 machine have been applied for sample manufacturing. A half-automated shot-peening process followed by a chemical and/or electrochemical polishing or Hirtisation® process has been applied in order to obtain lower surface roughness compared to their as-received states. Special emphasize has been taken on their tensile, fatigue, and fracture toughness properties. In addition, their stress corrosion cracking (SCC) behaviour including microstructural analysis using HR-SEM have been investigated.

Alpha-B-Crystallin, a member of the small heat shock family of proteins, has been implicated in a variety of cardiomyopathies and in normal cardiac homeostasis. It is known to function as a molecular chaperone, particularly for desmin, but also interacts with a wide variety of additional proteins. The molecular chaperone function is also enhanced by signal-dependent phosphorylation at specific residues under stress conditions. Naturally occurring mutations in CRYAB, the gene that encodes alpha-B-crystallin, have been suggested to alter ionic intermolecular interactions that affect dimerization and affect chaperone function. These mutations have been associated with myofibrillar myopathy, restrictive cardiomyopathy, and hypertrophic cardiomyopathy, and promote pathological hypertrophy through different mechanisms such as desmin aggregation, increased reductive stress or activation of calcineurin-NFAT signaling. This review will discuss the known mechanisms by which alpha-B-crystallin functions in cardiac homeostasis and the pathogenesis of cardiomyopathies and provide insight into potential future areas of exploration.

Active vitamin D derivatives (VDDs) – 1α,25-dihydroxyvitamin D3/D2 and their synthetic analogs – are well-known inducers of cell maturation with the potential for differentiation therapy of acute myeloid leukemia (AML). However, their dose-limiting calcemic activity is a significant obstacle to using VDDs as an anticancer treatment. We have shown that different activators of the NF-E2-related factor-2/Antioxidant Response Element (Nrf2/ARE) signaling pathway, such as the phenolic antioxidant carnosic acid (CA) or the multiple sclerosis drug monomethyl fumarate (MMF), synergistically enhance the antileukemic effects of various VDDs applied at low concentrations in vitro and in vivo. This study aimed to investigate whether glutathione, the major cellular antioxidant and the product of the Nrf2/ARE pathway, can mediate the Nrf2-dependent differentiation-enhancing activity of CA and MMF in HL60 human AML cells. We report that glutathione depletion using L-buthionine sulfoximine attenuated the enhancing effects of both Nrf2 activators concomitant with downregulating vitamin D receptor (VDR) target genes and the activator protein-1 (AP-1) family protein c-Jun levels and phosphorylation. On the other hand, adding reduced glutathione ethyl ester to dominant negative Nrf2-expressing cells re-stored both the suppressed differentiation responses and the downregulated expression of VDR protein, VDR target genes, as well as c-Jun and P-c-Jun levels. Finally, using the transcription factor decoy strategy, we demonstrated that AP-1 is necessary for the enhancement by CA and MMF of 1α,25-dihydroxyvitamin D3-induced VDR and RXRα protein expression, transactivation of the vitamin D response element, and cell differentiation. Collectively, our findings suggest that glutathione mediates, at least in part, the potentiating effect of Nrf2 activators on VDDs-induced differentiation of AML cells, likely through the positive regulation of AP-1.

Biotechnological potential of Thermoanaerobacter strain AK15 to produce ethanol and valuable alcohols from carbohydrates and amino acids were evaluated in present study. The strain is highly ethanologenic, producing a maximum of 1.57 mol ethanol per mol of glucose degraded at high liquid-gas phase ratios. The strain degrades most of the sugars tested as well as starch and pretreated hydrolysates of biopolymers (Whatman paper, newspaper, Timothy grass, Rhubarb leaves, and several macroalgae species) to ethanol mainly. The strains degraded serine and threonine when used as a single substrate, producing mainly acetate and ethanol as end products, and the branched-chain amino acids (leucine, isoleucine, valine) when cultivated in the presence of thiosulfate. The main end products from branched-chain amino acids were a mixture of their corresponding branched-chain fatty acids and alcohols. Finally, the strain was also shown to use butyrate as an electron sink during glucose degradation resulting in the reduced product butanol in addition to end products produced from glucose. Thus, strain AK15 is a promising candidate for ethanol and fine chemical production from a range of lignocellulosic and algal biomass.

Any Hospital’s primary goal is to restore human health and save lives through health services provided to patients, but at the same time, hazardous wastes are produced. Inconsistent management of unsafe wastes might cause adverse effects and other issues to workers, the environment and public health. Segregation is considered the critical stage for a successful Healthcare Waste Management. Mixing hazardous waste with non-hazardous waste will be avoided by correctly applying practices at the segregation stage. This study aimed to assess personnel’s knowledge about Infectious Medical Waste and segregation practices used at six wards in Nicosia General Hospital. An analytical cross-sectional study was conducted, and data were collected through a structured self-administered questionnaire. The Statistical Package of Social Science (SPPS) version 25 was used with a minimum statistical significance α=0.05. The study population was nurses, nurse assistants, ward assistants and cleaners working at the study wards. Out of 191 questionnaires, 82 were received, with a response rate of 42.93%. Most participants were female (72%) and nurses (85,4%). Participants had medium to good knowledge about Infectious Medical Waste management and good knowledge regarding segregation practices applied in their ward. Segregation was not carried out as it should have since most participants stated that Infectious Medical Wastes were mixed with non-hazardous waste. Correct answers given by the participants regarding color-coding of different Healthcare Waste categories was 67.5%, and only four answered correctly to all questions. Although participants knew segregation practices and the colour-coding process applied for Healthcare Waste, they didn’t use them satisfactorily. They applied methods regarding segregation without specific training, knowledge and guidance. Due to the issue's importance, training programs must be implemented and performed.

Silver eel were sampled in 1981 and 1983 in River Brede, Denmark, with outlet to the North Sea. Yellow eel in River Køge-Lellinge, Denmark, with outlet to the Baltic Sea were sampled 1965-1968. Silver eel were aged by burning the otoliths. Silver male ages varied from 4 to 25 years, lengths 30.8 to 45.3 cm, and female silver eel varied from 7 to 25 years, lengths 42.3 to 77.3 cm. von Bertalanffy trajectories of length-at-age of male and female yellow eel were calculated in both rivers. Younger yellow eel had significantly higher annual growth rate compared to older age groups, and females grew significantly faster than males. Two models for natural mortality M were used to estimate number of glass eel needed to produce number of silver eel for each sex and silver age group. Annual silver eel production from River Brede Å was 49.2 kg ha-1, demanding 2,894 glass eel ha-1 and in River Køge-Lellinge, the silver eel production was 48.5 kg ha-1, demanding 5,570 glass eel ha-1. It was calculated that one (0.29 g) thousand glass eel contribute to 8.8 kg silver eel in River Køge-Lellinge, and 17.0 kg silver eel in River Brede. To fulfill the Danish EMP in rivers requires annual stocking of 33 tons or 9.4 million reared on-grown eel (3.5 g) to compensate for 183 tons lost silver eel.

Food insecurity is an economic and social condition involving limited or uncertain access to food. The problem of food insecurity in communities is influenced by economic conditions, food deserts, and barriers to accessing healthy food. Individuals experiencing food insecurity often endure concurrent problems of financial instability, hunger, and poor mental and physical health. Public and non-profit services in the U.S., such as the federally supported Supplemental Nutrition Assistance Program (SNAP) and community food banks, provide food-related assistance to individuals who are at a high risk of experiencing food insecurity. Unfortunately, many individuals who qualify for these services still experience food insecurity due to barriers preventing them from accessing food. Effective approaches for removing barriers that prevent individuals from accessing food are needed to mitigate the increased risk of chronic disease among vulnerable populations. This study tested a novel food insecurity intervention called FINDING-Food, which stands for Frequent Informational Nudges Directing Individuals to Needed Goods. Informational nudges in the intervention promoted food security through the elimination of information barriers to accessing food. The intervention used in this mixed-methods feasibility study consisted of informational nudges in the form of weekly text messages that were sent to food pantry clients experiencing food insecurity. The study aims were to test the efficacy and acceptability of the intervention by examining whether the informational nudges could enhance food pantry utilization, increase SNAP registration, and promote food security. Quantitative study results showed a lower prevalence of food insecurity in the intervention group than the control group at the end of the study. Qualitative findings revealed how the intervention group found the text messages to be helpful and informative. These study findings can enhance future food insecurity interventions aiming to eliminate barriers that prevent individuals who are food insecure from accessing healthy food.

Modeling the flow of polymer solutions requires knowledge at various length and time scales. The macroscopic behavior is described by the overall velocity, pressure and stress. The polymeric contribution to the stress requires knowledge of the evolution of polymer chains. In this work, we use a microscopic model, the finitely extensible nonlinear elastic (FENE) model, to capture the polymer behavior. The benefit of microscopic models is they remain faithful to the polymer dynamics without information loss via averaging. The downside is the computational cost needed to solve the thousands to millions of differential equations describing the microstructure. We thus describe a multiscale flow solver that utilizes GPUs for massively parallel, efficient simulations. We compare and contrast the microscopic model with its macroscopic counterpart under various flow conditions. In particular, significant differences are observed under nonlinear flow conditions, where the polymers become highly stretched and oriented.

Plasma technology shows tremendous potential for revolutionizing oncology research and treatment. Reactive oxygen and nitrogen species, electromagnetic emissions generated through gas plasma jets, have attracted significant attention due to their selective cytotoxicity towards cancer cells. To leverage the full potential of plasma medicine, researchers have explored the use of mathematical models and various subsets of machine learning, such as reinforcement learning, and deep learning. This review emphasizes the significant application of AI algorithms in the adaptive plasma system, paving the way for precision and dynamic cancer treatment. Realizing the full potential of AI in plasma medicine, requires research efforts, data sharing and interdisciplinary collaborations. Unravelling the complex mechanisms, developing real-time diagnostics, and optimizing AI models will be crucial to harness the true power of plasma technology in oncology. The integration of personalized and dynamic plasma therapies, alongside AI and diagnostic sensors, presents a transformative approach to cancer treatment with the potential to improve outcomes globally.

Background: Food insecurity is an ongoing problem in the U.S. with implications for health problems and social disadvantages. Past food insecurity intervention studies have targeted barriers to accessing healthy food. Although, information barriers have not been adequately addressed by food insecurity interventions. Methods: This qualitative study involved testing a text message as an informational nudge through interviews among adults in the southwest U.S. (n = 10). Interview questions focused on the message content, persuasiveness, relevancy, clarity, and details that participants liked and disliked. A qualitative content analysis of interview responses then highlighted any necessary modifications to the text message. Results: Interview responses highlighted that the message conveyed details about how to access food assistance resources. The message was perceived as informative, clear, and friendly. Participants highlighted the need for better spacing in the message layout, more details about the Supplemental Nutrition Assistance Program (SNAP), and why SNAP is relevant. Conclusion: Text message readability and informativeness were common concerns raised during interviews. Participant-informed modifications to the text message were applied in preparation for using the message in a food insecurity intervention. Future food insecurity research efforts should similarly test novel interventions to ensure the intervention is acceptable for the target population.

We explicate a traumatized child's narcissistic defense against trauma. Following a review of psychoanalytic understandings of trauma we explore the invocation of narcissistic defenses against trauma. The phenomenon of Nachträglichkeit or après-coup is explored, and the paper concludes with clinical illustration drawn from the experience of a young boy who suffered significant separation trauma during the Holocaust.

Rapid in vitro assessment of antimicrobial drug efficacy under clinically relevant pharmacokinetic conditions is an essential element of both drug development and clinical use. Here we present an overview of a novel integrated methodology for rapid assessment of such efficacy, particularly against emergence of resistant bacterial strains, as jointly researched by the authors in recent years. This methodology enables rapid in vitro assessment of antimicrobial efficacy of a single or multiple drugs in combination, following clinically relevant pharmacokinetics. The proposed methodology entails (a) automated collection of longitudinal time-kill data in an optical-density instrument; (b) processing of collected time-kill data with the aid of a mathematical model to de-termine optimal dosing regimens under clinically relevant pharmacokinetics for a single or mul-tiple drugs; and (c) in vitro validation of promising dosing regimens in a hollow fiber system. Proof-of-concept of this methodology through a number of in vitro studies is discussed. Future directions for refinement of optimal data collection and processing are discussed.

We exploit the properties of complex time to obtain an analytical relationship based on considerations of causality between the two conserved quantities of a system’s Hamiltonian and its Entropy Production. In natural units, when complexified, the one is simply the Wick-rotated complex-conjugate of the other. A Hilbert transform relation is constructed in the formalism of Quantitative Geometrical Thermodynamics which enables system irreversibility to be handled analytically within a framework that unifies both the microscopic and macroscopic scales, and which also unifies the treatment of both reversibility and irreversibility as complementary parts of a single physical description. In particular the thermodynamics of two unitary entities are considered: the alpha particle which is absolutely stable (that is, trivially reversible with zero entropy production), and a black hole whose absolute disequilibrium (unconditional irreversibility) is characterized by a non-zero entropy production for which we show an alternate derivation confirming our previous one (Universe 7, 2021, 325). The thermodynamics of a canonical decaying harmonic oscillator are also considered. In this treatment the complexification of time also enables a meaningful physical interpretation of both “imaginary time” and “imaginary energy”.

In this study, a numerical simulation of fluid flow through railway ballast in the time domain is presented, providing a model for unsteady-state flow. It is demonstrated that the position of the free surface with respect to time can also be used to solve the steady flow case. The effect of ballast fouling is included in the model to capture the realistic behavior of railway ballast, which is critical to understanding the impact of flooding. A thorough comparison with a range of previous studies, including theoretical and experimental approaches, is made and very close agreement is obtained. The significant impact of ballast fouling on fluid flow and its potential consequences for railway infrastructure are highlighted by the simulation. Valuable insights into the behavior of water flow through porous media and its relevance to railway ballast management are offered by this study.

The SARS–CoV-2 infection has caused both acute and chronic COVID–19 disease during the recent pandemic with emerging more transmissible SARS–CoV–2 Omicron variants (BQ1 and XBB1) that have increased demands for more effective immunogens and therapeutic approaches to protect the lives of numerous SARS–CoV-2 affected individuals and reduce overall disease burden that could be affected by concurrent other pathogens causing diseases. Following a worldwide campaign of mass vaccination, there is still a significant demand to quell the harmful effects of novel SARS–CoV–2 infections due to higher mutation rates within specific areas of the SARS–CoV-2 domain, leading to enhanced viral entry, especially within individuals with one or more significant comorbidities, and there is still a dilemma of how prevention of future pandemics will occur as within host animal mutations and cross species transfer naturally occurs. Concerns intersect at a specific point; a gained evolutionary ability of several viruses over the previous centuries to remain undetected during the first stages of infection by means of capping the 5' end of their DNA and RNA genes respectively. This may occur by reducing the rate of host Type I and Type III Interferons (IFN) cellular synthesis, that would usually occur and affect both apoptotic pathways, that facilitate viral replication and clearance, as well as immune cells, that process and present pathogenic antigen epitopes. Furthermore, although methods of vaccination exist, other methods in clinical development remain that could evoke an immune response in different cellular, serum or mucosal compartments being cellular, serum and mucosal that evoke differential antibody responses. Antibodies are classed as natural and synthetic. Natural antibodies are further classified into neutralizing and non-neutralizing, whilst synthetic antibodies are also further classified into monoclonal and polyclonal. As a result of single cell study transcriptome research, viruses do utilize an array of protein receptors for receptor-mediated cellular entry. This, therefore suggests that potential differential production of antibody immunoglobulins (Ig) within serum and mucosal areas remains affected by cytokines, adhesion molecules and chemokines that can be upregulated or downregulated upon host viral infection. Serum plasma antibodies can be multimeric that may not efficiently cross the nasal epithelium cell layer, therefore offering less protection against mucosal inflammation due to mucin proteins. On the other hand, antibodies produced by mucosal plasma cells at epithelial surfaces are known to provide effective immune responses in some viral infections. The existence of developments that stimulate mucosal immune responses has so far only been seen with influenza nasal immunogens. Nevertheless, scientists developed ways of immunization and early treatment worldwide that generally showed good success rates and fewer risks of adverse events, and the still early present stages of COVID-19 research should also be taken into consideration. For example, the administration of human interferons I and III into the nasal mucosa cellular layer, as key mediators of anti–viral activity, can stimulate cellular activity to train the innate and adaptive immune system cells to develop and appropriately stimulate an adequate immune response through B and T cells. Recently, it was discovered that specific plants secrete proteins that also stimulate the production of Type I Interferons. It might be that focusing on directly offering the immune system the information about the genetics and protein structure of the pathogen, rather than training its first-line mechanisms to develop faster, excessively increases its specificity, making it reach a level that brings the virus the opportunity to evolve and escape previously-developed host immune mechanisms. Naturally-selected polymorphic viruses through genetic recombination pose challenges to traditional concepts of cellular and molecular immune system neutralization of these viruses during the first stages of cellular infection. It is until the scientific community realizes this potentially crucial aspect that we will probably continue to face serious epidemics and pandemics of respiratory diseases over the coming several decades, evidenced with dengue fever and more recently monkeypox. Type I IFNs tend to be produced faster than Type III IFNs, and the first induce slightly more abundant pro-inflammatory signals than the latter, meaning that type III IFNs, if produced early, may further decrease the extent of excessive proinflammatory signals. Hence, we believe that nasal sprays containing a low dosage of Type I and Type III IFNs not only represent a relevant COVID-19 therapeutic, but also a potential unknown modulatory therapy of the future. Of note, it has been indicated that IFN I and / or III display significant immunizing and early therapeutic effects for other viral evoked diseases like Influenza (Influenza (A)H1N1), rabies (Rabies lyssavirus), measles (Measles virus), rubella (Rubivirus rubellae), Hepatitis B, HIV-induced AIDS, Ebola, Marburg, as well as bacterial diseases, such as lower respiratory tract infectious diseases induced by Haemophilus influenzae, Streptococcus pneumoniae and Staphylococcus aureus, and a number of oncological diseases, like hepatic melanoma.

Maternal infectious disease may pose considerable challenges to the fetal health due to the distribution of important elements of the sanguine and lymphatic system from the mother via the umbilical cord. The mother and the fetus have a degree of interdependence that is similar to the one between the eukaryotic cell and the mitochondrion, particularly during the first half term of the pregnancy, which explains the increased appetite of the expecting mother during the first stages of the fetal development. There is a solid bridge between the adaptive immune system and the encephalon that was only discovered a few decades ago. As a result, scientists may still be in the introductory stages of research, and there might be a significant and profound degree of association between the immune system and a healthy neurological development. There is a significant link between the onset of significant maternal infectious disease and the onset of neurodevelopmental disease in the fetus, and virtually all immune cells play major roles in the promotion and inhibition of neurogenesis alike. Likewise, there is a probability that maternal infectious diseases during pregnancy represent a risk factor of fetal neurodevelopmental disease, as a pressurised development of the adaptive immune memory could result in a pressurised or inhibited neurological development, which both can result in a delayed development of certain sub-regions of the brain. For example, the fetus may display poorer social abilities and sharp analytical skills later in life, which is an important sign of neurodevelopmental disease. A pressurised development of the adaptive immune memory could not require the development of a significant form of disease, but rather just a sharp rate of immune preparation against several important pathogenic agents during the introductory stages of life, when the encephalon experiences the sharpest increase rate in development. The problem per se is not the process of immunisation, but a much sharper process of immunisation over the first stages of life in case of an exposure to one dangerous pathogen or more numerous kinds of pathogens and antigens that normally cause moderate disease morbidity. The more dangerous the microbe is, the sharper the development of the adaptive immune memory will be, and the same happens in the case of an increased number of infectious microbes and antigens that infected the cells of the mothers and the fetuses in cause, and this may, in the majority of the situations, still be the case even if the pathogens are already significantly weakened or lifeless, given that the gain of adaptive immune memory alone constitutes an important factor of neurogenesis and an increased rate of neurological development, and that the infant will become almost or fully protected against the pathogens in cause, despite not having had experienced the disease beforehand. In this case, neurodevelopmental delays are possibly not caused by an impaired neurogenesis, but by an excessive one, whilst maternal infection-associated neurodevelopmental delays may be caused by an impaired neurogenesis. Nevertheless, the aetiology of immunity-related neurodevelopmental delays may be more complex in nature and implicate a chronological and spatial sequence of induced excedentary and deficitary rates of neurogenesis, hence reflecting the incredibly complex nature and various forms of neurodevelopmental disease. It is important to mention that a single dose of infant immunisation brings significantly lower risks of adverse neurological events than the onset of a significant maternal infectious disease during pregnancy. The objective of paediatric neuro-immunological studies may be to improve the understanding of the association between a healthy immune developmental rate and a balanced ratio of the developmental rates of important brain regions and sub-regions.

It has been shown that the Micro-Rain Radar (MRR) can be used to derive rainfall rates every 10 m over a depth of 1.28 km using the mean vertical air velocity corrected Doppler raindrop fall speed spectra. Furthermore, it has been shown that by assuming a reasonable advection velocity for the rain, these data can be analyzed to produce spatial radial power spectra often readily fit using a power function. Previous work has shown, however, that each spectrum applies only to each particular set of data and usually lacks the statistical qualifications necessary to be considered generally applicable. However, this limitation does not preclude the potential existence of other generalizations that can be used to explore the rainfall formation processes. The intent of this study, then, is to perform an initial look for such possible behaviors using time-height profiles of the rainfall rate. It is found that once the rainfall rate, R, exceeds about 20 mm h-1, there is, apparently, an associated flattening of the spectra with increasing R so that the smaller scales play an ever increasingly important role in such rain near the ground perhaps reflecting the increasing importance of such scales in the formation of pockets of more intense convective rain. The true generality of this finding needs additional scrutiny using more data particularly from two spatially separated MRR as is currently under preparation.

Kynurenine or tryptophan catabolite (TRYCAT) pathway contributes to the pathophysiology of major depression disorder (MDD) and major depressive episodes (MDE) in bipolar disorder and suicidal behaviors. The consequences of the overactivation of this pathway large reduced tryptophan (TRP) levels in peripheral blood and the CNS and increased levels of neurotoxic TRYCATs including kynurenine (KYN), 3-hydroxy kynurenine (3HK), quinolinic acid (QA), xanthurenic acid (XA), and picolinic acid (PA). However, other TRYCATs are protective, such as kynurenic acid (KA) and anthranilic acid (AA). Inflammation and cell-mediated immune activation along with oxidative and nitrosative stress (O&NS) may stimulate the first and rate-limiting enzyme of this pathway, namely indoleamine-2,3-dioxygenase (IDO). Therefore, during depression, balancing neuroprotective versus neurotoxic TRYCATs and balancing activation of the immune response system (IRS) versus the compensatory immune response system is crucial for achieving better treatment outcomes. Furthermore, targeting the causes of TRYCAT pathway activation (immune activation and O&NS) is probably the most effective strategy to treat depression. In the present review, we aim to provide a comprehensive explanation of the impact of TRYCATs in terms of pathophysiology and treatment of MDD and MDE.

Amongst the advantages of using Worldwide Interoperability Microwave Access (WiMAX) technology at the last-mile level as access technology include an extensive range of 50 km Line of Sight (LOS), 5 to 15 km Non-Line of Sight and few infrastructure installations compared to other wireless broadband access technologies. Despite positive investments in ICT fibre infrastructure by developing countries, including Botswana, servicing end-users is subjected to high prices and service disparities. The alternative, the Wi-Fi hotspot initiative by the Botswana government, falls short as a solution for last-mile connectivity and access. This study used OPNET simulation Modeller 14,5 to investigate whether Botswana’s national broadband project could adopt WiMAX IEEE 802.16e as an access technology. Therefore, using the simulation method, this paper evaluates the WiMAX IEEE 802.16e/m over three subscriber locations in Botswana. The results obtained indicate that the deployment of the WiMAX IEEE 802.16e standard can solve most of the deployment issues and access at the last-mile level. Although the findings suggest that WiMAX IEEE 802.16e is more suitable for high-density areas, it could also solve rural areas’ infrastructure development challenges and provide the required high-speed connectivity access. However, unlike the Wi-Fi initiative, which requires more infrastructure deployment and less on institutional and regulatory frameworks, the deployment of WiMAX IEEE802.16e requires institutional and regulatory standards.

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disorder affecting 1 in 500 people in the general population. Although characterized by asymmetric left ventricular hypertrophy, cardiomyocyte disarray and cardiac fibrosis, HCM is in fact a highly complex disease with heterogenous clinical presentation, onset and complications. While HCM is generally accepted as a disease of the sarcomere, variable penetrance in families with identical genetic mutations challenges the monogenic origin of HCM and instead implies a multifactorial cause. Furthermore, large scale genome sequencing studies revealed that many genes previously reported as causative of HCM in fact have little or no evidence of disease association. These findings thus call for a re-evaluation of the sarcomere-centered view of HCM pathogenesis. Here, we summarize our current understanding of sarcomere-independent mechanisms of cardiomyocyte hypertrophy, highlight the role of extracellular signals in cardiac fibrosis, and propose an alternative but integrated model of HCM pathogenesis.

Many (if not a very large number) of metals and alloys evince substantial softening with torsion deformation to strains not usually achievable in tension. Of course, softening has long been observed by discontinuous dynamic recrystallization (DDRX) but this paper will discuss cases where softening is associated by texture development with large-strain deformation that is not reliant on changes in the dislocation hardening. This paper reviews the work of the current authors on FCC metals and alloys in this area and extends to a new discussion of BCC and HCP cases.

Competition over environmental and natural resources characteristically lies at the heart of armed conflicts in Africa. It is also common knowledge that some companies dealing in products such as laptops, smart phones and jewellery; import minerals from conflict-affected areas, thereby indirectly fuelling conflicts in these areas or undermining human rights. For a continent endowed with natural resources including minerals, Africa has suffered the brunt of this predicament. This state of affairs has lent impetus to the adoption of several regulations geared towards curbing irresponsible business practices by companies relying on such minerals, the goal being, amongst others, to guarantee the protection of human rights. In May 2017, the European Union adopted Regulations intended to stop the importation of conflict minerals in Europe, debatably making giant strides in the direction of protection of human rights. These Regulations are to come into force in 2021. However, can these regulations advance the much-desired goal of protection of human rights in Africa on issues pertaining to conflict minerals? By analyzing the 2017 EU Regulations in light of previous regulations of a similar nature, the paper concludes that the said regulations constitute a weak normative framework and could in fact have unintended consequences on the fundamental rights of civilians in natural resource-rich conflict areas of Africa.

Land Use Land Cover (LULC) changes analysis is one of the most useful methodologies to understand how the land was used in the past years, what types of detections are to be expected in the future, as well as the driving forces and processes behind these changes. In Ethiopia, the rapidly changing of LULC is mainly due to population pressure, resettlement programs, climate change, and other human and nature-induced driving forces. Anthropogenic activities are the most significant factors adversely changing the natural status of the landscape and resources, which exerts unfavourable and adverse impacts on the environment and livelihood. The main goal of the present work is to review previous studies, discussing the spatio-temporal LULC changes in Ethiopian basins, to find out common points and gaps that exist in the current literature, to be eventually addressed in the future. Seventeen articles, published from 2011 to 2020, were selected and reviewed, focusing on LULC classification using ArcGIS and ERDAS imagine software by unsupervised and maximum likelihood supervised classification methods. Key informant interview (KII), focal group discussions (FGDs) and collection of ground truth data using ground positioning systems (GPS) for data validation were the major approaches discussed in most of the studies. All the analysed research showed that, during the last decades, Ethiopian lands changed to agricultural land use, waterbody, commercial farmland and built-up/settlement. Some parts of forest land, grazing land, swamp/wetland, shrubland, rangeland and bare/ rock out cropland cover class were changed to other LULC class types, mainly as a consequence of increasing anthropogenic pressure. In summary, these articles confirmed that LULC changes are a direct result of both natural and human influences. However, most of the study provided details of LULC for the past decades within a specific spatial location, while they did not address the challenge of forecasting future LULC changes at the basin scale.

Animal communication signals are regulated by multiple hormonal axes that ensure appropriate signal targeting, timing, and information content. The regulatory roles of steroid hormones and many peptide hormones are well understood and documented across a wide range of vertebrate taxa. Two recent studies have reported a novel function for leptin, a peptide hormone central to energy balance regulation: regulating communication signals of weakly electric fish and singing mice. With only limited evidence available at this time, a key question is just how widespread leptinergic regulation of communication signals is within and across taxa. A second important question is what features of communication signals are subject to leptinergic regulation. Here we consider the functional significance of leptinergic regulation of animal communication signals in the context of both direct and indirect signal metabolic costs. Direct costs arise from metabolic investment in signal production, while indirect costs arise from the predation and social conflict consequences of the signal’s information content. We propose a preliminary conceptual framework for predicting which species will exhibit leptinergic regulation of their communication signals and which signal features leptin will regulate. This framework suggests a number of directly testable predictions within and across taxa. Accounting for additional factors such as life history and reproductive strategies will likely require modification or elaboration of this model.

Double-spiral galaxies are common in the Universe. It is known that the logarithmic double spiral is a Maximum Entropy geometry and represents spiral galaxies well. It is also known that the virial mass of such a galaxy can be approximately determined from the entropy of its central supermassive black hole. But over time the black hole must accrete mass, and therefore the overall galactic entropy must increase. From the associated entropic Euler-Lagrange equation (forming the basis of the Principle of Least Exertion, and also enabling the application of Nöther’s theorem) we show that the galactic entropy production is a conserved quantity, and we derive an appropriate expression for the relativistic entropic Hamiltonian of an idealised spiral galaxy. We generalise Onsager’s celebrated expression for entropy production and demonstrate that galactic entropy production has two parts, one many orders of magnitude larger than the other, and where the smaller is comparable to the Hawking radiation of the central supermassive black hole. We conclude that galaxies cannot be isolated, since even idealised spiral galaxies have non-zero entropy production.

An effective empirical statistical method is developed to improve the process of mineral resource estimation of seabed polymetallic nodules and is applied to analyse the abundance of seabed polymetallic nodules in the Clarion Clipperton Zone (CCZ). The newly proposed method is based on three hypotheses as the foundation for a model of “Idealized Nodules”, which was validated by analysing nodule samples collected from the seabed within the Tonga Offshore Mining Limited (TOML) exploration contract. Once validated, the “Idealized Nodule” model was used to deduce a set of empirical formulae for predicting the nodule resources, in terms of Percentage Coverage and Abundance. The formulae were then applied to analysing a total of 188 sets of nodule samples collected across the TOML areas, comprising box-core samples and towed camera images collected by one of the authors and detailed in [4]. The analysis also relies upon detailed box-core sample measurements from other areas reported by [7]. Numerical results for resource prediction were compared with field measurements, and reasonable agreement has been achieved. The new method has the potential to achieve more accurate mineral resource estimation with reduced sample numbers and sizes. They may also have application in improving the efficiency of design and configuration of mining equipment.

Oxidative stress initiates and facilitates the disruption of the structural integrity of hepatic mitochondria, which leads to steatosis, steatohepatitis, fibrosis, and cirrhosis. It is now evident that mitochondrial dysfunction could be responsible for alcoholic liver disease (ALD). The challenge in treating ALD has been the limited availability of hepatoprotective agents and the lack of highly efficient delivery systems. Recent studies have shown that mitochondria-targeted therapies could address mitochondrial dysfunction (MD), which may greatly improve hepatoprotection and ALD treatment. This mini-review discusses the potential role of mitochondria-targeted antioxidants (MTAs) in the maintenance of hepatocellular integrity. This report also considers the mechanism of liver injury induced by alcohol and the progression of ALD from a mitochondrial oxidative damage perspective as well as the possible mechanistic actions of hepatoprotective antioxidants. Preliminary studies suggest the prospect of MTAs as anti-ALD and hepatoprotective agents.

Four decades of proteasome research have yielded extensive information on ubiquitin-dependent proteolysis. The archetype of proteasomes is a 20S barrel-shaped complex that does not rely on ubiquitin as a degradation signal but can degrade substrates with a considerable unstructured stretch. Since roughly half of all proteasomes in most eukaryotic cells are free 20S complexes, ubiquitin-independent protein degradation may coexist with ubiquitin-dependent degradation by the highly regulated 26S proteasome. This article reviews recent advances in our understanding of the biochemical and structural features that underlie the proteolytic mechanism of 20S proteasomes. The two outer α-rings of 20S proteasomes provide a number of potential docking sites for loosely folded polypeptides. The binding of a substrate can induce asymmetric conformational changes, trigger gate opening, and initiate its own degradation through a protease-driven translocation mechanism. Consequently, the substrate translocates through two additional narrow apertures augmented by the β-catalytic active sites. The overall pulling force through the two annuli results in a protease-like unfolding of the substrate and subsequent proteolysis in the catalytic chamber. Although both proteasomes contain identical β-catalytic active sites, the differential translocation mechanisms yield distinct peptide products. Non-overlapping substrate repertoires and product outcomes rationalize cohabitation of both proteasome complexes in cells.

Helmholtz energy of ice VII-X is determined in a pressure regime extending to 450 GPa at 300 K using local basis functions in the form of b splines. The new representation for the equation of state is embedded in a physics-based inverse theory framework of parameter estimation. Selected pressures as a function of volume from 14 prior experimental studies and two theoretical studies constrain the behavior of Helmholtz energy. Separately measured bulk moduli, not used to construct the representation, are accurately replicated below about 20 GPa and above 60 GPa. In the intermediate range of pressure, the experimentally determined moduli are larger and have greater scatter than values predicted using the Helmholtz representation. Although systematic experimental error in the experimental elastic moduli is possible and likely, the alternative hypothesis is a slow relaxation time associated with changes in proton mobility or the ice VII to X transition. A correlation is observed between anomalies in the pressure derivative of the predicted bulk modulus and previously suggested higher-order phase transitions. Improved determinations of elastic properties at high pressure would allow refinement of the current equation of state. More generally, the current method of data assimilation is broadly applicable to other materials in high-pressure studies.

Modularity is arguably one of the most influential theses guiding research on brain and cognitive function since phrenology. This paper considers the following question: is modularity entailed by recent Bayesian models of brain and cognitive function, especially the predictive processing framework? It starts by considering three of the most well-articulated arguments for the view that modularity and predictive processing work well together. It argues that all three kinds of arguments for modularity come up short, albeit for different reasons. The analysis in this paper, although formulated in the context of predictive processing, speaks to broader issues with how to understand the relationship between functional segregation and integration and the reciprocal architecture of the predictive brain. These conclusions have implications for how to study brain and cognitive function. Specifically, when cognitive neuroscience works within an acyclic Markov decision scheme, adopted by most Bayesian models of brain and cognitive function, it may very well be methodologically misguided. This speaks to an increasing tendency within the cognitive neurosciences to emphasise recurrent and reciprocal neuronal processing captured within newly emerging dynamical causal modelling frameworks. The conclusions also suggest that functional integration is an organising principle of brain and cognitive function.

The primary screening of hybridoma cells is a time-critical and laborious step during the development of monoclonal antibodies. Often critical errors occur in this phase, which supports the notion that the generation of monoclonal antibodies with hybridoma technology is difficult to control and hence a risky venture. We think that it is crucial to improve the screening process to eliminate most of the immanent deficits of the conventional approach. With this new microarray-based procedure, several advances could be achieved: Selectivity for excellent binders, high throughput, reproducible signals, avoidance of misleading avidity (multivalency) effects, and simultaneous performance of competition experiments. The latter can directly be used to select clones of desired cross-reactivity properties. In this paper, a model system with two excellent clones against carbamazepine, two weak clones and blank supernatant has been designed to examine the effectiveness of the new system. The excellent clones could be detected largely independent of the IgG concentration, which is unknown during the clone screening since the determination and subsequent adjustment of the antibody concentration is not possible in most cases. Furthermore, in this approach, the enrichment, isolation, and purification of IgG for characterization is not necessary. Raw cell culture supernatant can be used directly, even when fetal calf serum (FCS) or other complex media had been used. In addition, an improved method for the oriented antibody-immobilization on epoxy-silanized slides is presented. Based on the results of this model system, we conclude that this approach should be preferable to most other protocols leading to many of false positives, causing expensive and lengthy confirmation steps to weed out the poor clones.

This paper describes a new approach that can be used to determine the mechanical properties of unknown materials and complex material systems. The approach uses inverse finite element modelling (FEM) accompanied with a designed algorithm to obtain the modulus of elasticity, yield stress and strain hardening material constants of an isotropic hardening material model, as well as the material constants of the Drucker-Prager material model (modulus of elasticity, cap yield stress and angle of friction). The algorithm automatically feeds the input material properties data to finite element software and automatically runs simulations to establish a convergence between the numerical loading-unloading curve and the target data obtained from continuous indentation tests using common indenter geometries. A further module was developed to optimise convergence using an inverse FEM analysis interfaced with a non-linear MATLAB algorithm. A sensitivity analysis determined that the dual Spherical and Berkovich (S&B) approach delivered better results than other dual indentation methods such as Berkovich and Vickers (B&V) and Vickers and Spherical (V&S). It was found that better convergence values can be achieved despite a large variation in the starting parameter values and / or material constitutive model and such behaviour reflects the uniqueness of the dual S&B indentation in predicting complex material systems. The study has shown that a robust optimization method based on a non-linear least-squares curve fitting function (LSQNONLIN) within MATLAB and ABAQUS can be used to accurately predict a unique set of elastic plastic material properties and Drucker-Prager material properties. This is of benefit to the scientific investigation of properties of new materials or obtaining the material properties at different location of a part which might be not be similar due to manufacturing processes (e.g. different heating and cooling rates at different locations).

Cancers arise from the accumulation of somatic genome mutations, with varying contributions of intrinsic (i.e. genetic predisposition) and extrinsic (i.e. environmental) factors. For the understanding of malignant clones, precise information about their genomic composition has to be correlated with morphological, clinical and individual features, in the context of the available medical knowledge. Rapid improvements in molecular profiling techniques, the accumulation of large amount of data in genomic alterations in human malignancies and the expansion of bioinformatic tools and methodologies have facilitated the understanding of the molecular changes during oncogenesis, and their correlation with clinico-pathological phenotypes. Far beyond a limited set of "driver" genes, oncogenomic profiling has identified a large variety of somatic mutations; and whole genome sequencing studies of healthy individuals have improved the knowledge of heritable genome variation. Nevertheless, main challenges arise from the skewed representation of individuals from varying population backgrounds in biomedical studies, and also through the limited extend in which some cancer entities are represented in the scientific literature. Content analyses of oncogenomic publications could provide guidance for the planning and support of future studies aiming at filling prominent knowledge gaps.

Multiobjective optimization plays an increasingly important role in modern applications, where several criteria are often of equal importance. The task in multiobjective optimization and multiobjective optimal control is therefore to compute the set of optimal compromises (the Pareto set) between the conflicting objectives. The advances in algorithms and the increasing interest in Pareto optimal solutions have led to a wide range of new applications related to optimal and feedback control which results in new challenges such as expensive models or real-time applicability. Since the Pareto set generally consists of an infinite number of solutions, the computational effort can quickly become challenging which is particularly problematic when the objectives are costly to evaluate or when a solution has to be presented very quickly. This article gives an overview over recent developments in accelerating multiobjective optimal control for complex problems where either PDE constraints are present or where a feedback behavior has to be achieved. In the first case, surrogate models yield significant speed-ups. Besides classical meta-modeling techniques for multiobjective optimization, a promising alternative for control problems is to introduce a surrogate model for the system dynamics. In the case of real-time requirements, various promising model predictive control approaches have been proposed, using either fast online solvers or offline-online decomposition. We also briefly comment on dimension reduction in many-objective optimization problems as another technique for reducing the numerical effort.

To date, several different approaches are available to study sediment dynamics at reach or watershed scale, based on very different hypothesis. One of such assumptions, the so-called “morphodynamic equilibrium hypothesis” is becoming little unpopular for its embedded simplifications. The aim of this work is to demonstrate how this approach proves yet effective in modelling landscape morphodynamics at the watershed scale, for what concerns the longitudinal profile of a river and the sedimentary aspects. The application of a 1-D model based on the equilibrium hypothesis has been implemented for several large rivers worldwide. Geomorphological parameters have been analysed, which describe the evolution of longitudinal profile (concavity) and sediments characteristics (aggrading and fining), and the results show a reasonably good correspondence with qualitative estimation of the same parameters. At the scale of analysis and for the chosen systems, which show high inertia to geomorphological changes likely owing to their longitudinal extension, the model can detect where the present conditions reflect a big disturbance to the “natural equilibrium” thus allowing water managers to identify present issues to be addressed.

Objective: One of the major causes of cerebral ventricular shunt failure is proximal catheter occlusion. We describe a novel ventricular cerebrospinal fluid (CSF) flow replicating system that assesses pressure and flow responses to varied degrees of catheter occlusion. Methods: Ventricular catheter performance was assessed during conditions of partial and complete occlusion. The catheters were placed into a three-dimensionally printed phantom ventricular replicating system. Artificial CSF was pumped through the ventricular system at a constant rate of 1 ml/min to mimic CSF flow, with the proximal end of the catheter in the phantom ventricle. Pressure transducer and flow rate sensors were used to measure intra-phantom pressure, outflow pressure and CSF flow rates. The catheters were also inserted into silicone tubing and pressure was measured in the same manner for comparison with the phantom. Results: Pressure measured in the phantom ventricle did not change when the outflow of the ventricular catheter was partially occluded. However, the intraventricular phantom pressure significantly increased when the outflow catheter was 100% occluded. Flow through the catheter showed no significant difference in rate with any degree of partial occlusion of the catheter. At the distal end of the partially occluded catheters, there was less pressure compared with the nonoccluded catheters. This difference in pressure in partially occluded catheters correlated with the percentage of catheter hole occlusion. Conclusions: Our model mimics physiological dynamics of the CSF flow in partially and completely obstructed ventricular catheters. We found that partial occlusion of the catheter had no effect on CSF flow rate, but did reduce outflow pressure of the catheter.

Ovarian lymphoma is an infrequent disease, accounting for less than 1% of all non-Hodgkin lymphoma diagnosis. Symptoms include abnormal vaginal bleeding or discharge, abdominal pain, and urinary obstruction due to the large mass. In our case, a 60-year-old woman, underwent a total abdominal hysterectomy and bilateral salpingo-oophorectomy, as she presented with low-grade follicular lymphoma (FL) in both the ovaries, and the left ovary was observed to be enlarged. The tumor is categorized as lymphoma based upon immunohistochemical markers. Computed tomography (CT) scan of the chest, abdomen, and pelvis and bone marrow biopsy are important for the staging of primary lymphoma of the ovary. The first-line chemotherapy regimen includes rituximab, cyclophosphamide, doxorubicin hydrochloride (hydroxydaunorubicin), vincristine sulfate (Oncovin), and prednisone (R-CHOP) for rapidly proliferative non-Hodgkin lymphoma (NHL). Lymphomas with slower growth patterns can be treated with Bendamustine-Rituximab and don’t need aggressive R-CHOP treatment.

The alteration of natural land cover to impervious surfaces during development increases stormwater runoff. Stormwater Control Measures (SCMs) are used to manage water quantity and enhance water quality by restoring the hydrologic cycle altered by development. Often, SCMs have an outflow pipe to handle overflows or to manage the release of water detained when infiltration is not possible. Traditionally, these are static controls (e.g. a small orifice is used to restrict the volume of outflow), however, these systems can be improved by instituting real-time controls (RTC). RTC improve the functionality of SCMs by dynamically controlling outflows to adjust to environmental conditions. A major impediment to the widespread implementation of RTC is the high cost of installation and operation. This study utilized machine learning methods to develop a forecasting approach for the implementation of low-cost RTC that were implemented on a programmable gate of the outlet structure of a multi-stage basin in southeastern Pennsylvania. The goals were to decrease the peak flow exiting the basin during rain events, increase the volume of water detained, decrease the number of overtopping events, maintain healthy vegetation in the basin, and protect the downstream vegetation from erosion. Multiple popular data science algorithms were evaluated including multiple linear regression and long short-term memory. These algorithms were used with a dataset, which consisted of four years of historical sensor data, collected in 5-minute intervals, to train models to predict water levels to optimize operations. The accuracy of 30 models with three different methods of handling missing values were compared. A long short-term memory model configured with a 30-minute lead time produced the best results. Having an approximate same lag time of 30 minutes for the contributing drainage area of the SCM provided a sufficient RTC functioning period to improve the performance of the outlet structure.

This paper reviews the appearance of joint lesions during arthroscopic surgery of inter-est to the arthroscopic surgeon and their interpretation within the continuum of joint disease. It also points out the relevance of surgical findings as well as giving directions to the surgeon as to how to approach an appropriate decision-making process during an arthroscopic procedure and what therapeutic options are optimal.

The Principle of Indifference (“PI”: the simplest non-informative prior in Bayesian probability) has been shown to lead to paradoxes since Bertrand (1889). Von Mises (1928) introduced the “Wine/Water Paradox” as a resonant example of a “Bertrand paradox”, and which has been presented as demonstrating that the PI must be rejected. We now resolve these paradoxes by a Maximum Entropy (MaxEnt) treatment of the PI that also includes information provided by Benford’s “Law of Anomalous Numbers” (1938). We show that the PI should be understood to represent a family of informationally-identical MaxEnt solutions; each solution being identified with its own explicitly justified boundary condition. In particular, our solution of the Wine/Water Paradox exploits Benford’s Law to construct a non-uniform distribution representing the universal constraint of scale invariance, which is a physical consequence of the Second Law of Thermodynamics.

Academic and corporate research has been focusing on analyzing stock performances, financial markets, and investment strategies for decades. According to Lynch and Rothchild (1989), certain investments can be described as plays. In this work, the authors use the term for investments in value stocks, spin-offs, and turnarounds to analyze the long-term stock performance and risk-adjusted excess returns of up to five years for those stocks. Additionally, stocks with a supe-rior return performance are identified within an investment play based on low P/E and P/B mul-tiples. The study finds that value stocks, spin-offs, and turnarounds outperform the S&P 500 on average on a one-, three- and five-year investment horizon. The analysis of the three investment plays confirms earlier studies that investment plays constitute a profitable investment opportunity. Moreover, the research exemplifies that private investors could achieve an excess return (alpha) through a passive buy-and-hold investment strategy. Overall, the analysis provides a deeper in-sight into the long-term performance of value stocks, spin-offs, and turnarounds.

The Golden ratio is an irrational number that has a tendency to appear in many different scientific and artistic fields. It may be found in natural phenomena across a vast range of length scales; from galactic to atomic. In this review, the mathematical properties of the Golden ratio are discussed before exploring where in nature it has been found; beginning at astronomical scales and progressing to smaller lengths, until reaching those of atomic and quantum physics. In making such a tour across length scales, it is illustrated just how prevalent this single number is within the natural universe.

A realistic approach for gathering high-resolution observation of the rainfall rate, R, in the vertical plane is to use data from vertical pointing Doppler radars. After accounting for the vertical air velocity and attenuation, it is possible to determine the fine, spatially resolved drop size spectra and to calculate R for further statistical analyses. The first such results in a vertical plane are reported here. Specifically, we present results using MRR-Pro Doppler radar observations at resolutions of ten meters in height over the lowest 1.28 km as well as ten seconds in time over four sets of observations using two different radars at different locations. Both correlation functions and power spectra are useful for translating observations and numerical model outputs of R from on one scale down to other scales that may be more appropriate to particular applications such as flood warnings and soil erosion, for example. However, it was found in all cases that while locally applicable radial power spectra could be calculated, because of statistical heterogeneity, most of the power spectra lost all generality and proper correlation functions could not be computed in general except for one 17 minute interval. Nevertheless, these results are still useful since they could be combined to develop catalogs of power spectra over different meteorological conditions and in different climatological settings and locations. Furthermore, even within the limitations of these data, this approach is being used to gain a deeper understanding of rainfall to be reported in a forthcoming paper.

Martensitic steels are used at a wide range of strength levels in environments which expose them to hydrogen or water vapor over a large range of partial pressures and temperatures. Hydrogen can cause catastrophic failures under many seemingly benign conditions. The effect of hydrogen on the dimension stability of high strength martensitic steels under such conditions has been poorly understood, and existing models do not seem to adequately account for it. Experiments were conducted to measure the variation in volume due to the uptake of hydrogen of such steels under near-ambient conditions, and the results were compared to theoretical estimates derived from the density of defects acting as hydrogen traps. Based on these results a new model for hydrogen embrittlement was developed. The hydrogen lattice dilation (HLD) model isolates volume expansion as a primary driver of hydrogen embrittlement. It provides and distinguishes two modes of failure acceleration: the fast, brittle, stress-intensity independent cracking under higher static crack loading, and a slower, highly stress-intensity dependent tearing mode at lower stress intensity. The relationship between the two is explained, as is how hydrogen absorption by defects accounts for the crack threshold and crack velocity of each.

Hypertrophic Cardiomyopathy (HCM) is a common inherited disorder characterized by unexplained left ventricular hypertrophy, with or without left ventricular outflow tract (LVOT) obstruction. Single nuclei RNA-sequencing (snRNA-seq) of both obstructive and nonobstructive HCM patient samples have revealed alterations in communication between various cell types but a direct and integrated comparison between the two HCM phenotypes has not been reported. We performed a bioinformatic analysis of HCM snRNA-seq datasets from obstructive and nonobstructive patient samples to identify differentially expressed genes and distinctive patterns of intercellular communication. Differential gene expression analysis revealed 37 differentially expressed genes, predominantly in cardiomyocytes but also in other cell types, relevant to aging, muscle contraction, cell motility and the extracellular matrix. Intercellular communication was generally reduced in HCM, affecting the extracellular matrix, growth factor binding, integrin binding, PDGF binding and SMAD binding, but with increases in adenylate cyclase binding, calcium channel inhibitor activity, and serine-threonine kinase activity in nonobstructive HCM. Increases in neuron to leukocyte and dendritic cell communication, in fibroblast to leukocyte and dendritic cell communication and in endothelial cell communication to other cell types, largely through changes in expression of integrin-b1 and its cognate ligands, were also noted. These findings indicate both common and distinct physiological mechanisms affecting the pathogenesis of obstructive and nonobstructive HCM and provide opportunities for personalized management of different HCM phenotypes.

Rural electrification rate (RER) in Africa is still low to date. Several countries in Sub-Saharan Africa have tried to address this problem using conventional single-phase two-wire or three-phase three-wire systems, however at large costs due to the nature of dispersed rural load centers, low load demand, and low population density. Another solution of off-grid generation creates associated health problems. Therefore, this paper undertakes a review of a single wire earth return (SWER) network as a RER improvement solution. The paper undertakes intensive literature review to elucidate challenges and solutions to the implementation of SWER technology. Advantages of SWER technology discussed make it the choice for RER improvement in Sub-Saharan African countries. After that, a case study is selected in rural Tanzania, and a preliminary SWER network design is undertaken.

Vaccination is widely regarded as a cornerstone in animal or herd health and infectious disease management. Nineteen vaccines against the major pathogens implicated in bovine respiratory disease are registered for use in the UK by the Veterinary Medicines Directorate (VMD). However, despite annual prophylactic vaccination, bovine respiratory disease is still conservatively estimated to cost the UK economy approximately £80 million per annum. This review examines the vaccine types available, discusses the surrounding literature and scientific rationale of the limitations and assesses the potential of novel vaccine technologies.

The microtubule-associated protein TAU is sorted into the axon in healthy brain neurons. Somatodendritic missorting of TAU is a pathological hallmark of many neurodegenerative diseases called tauopathies, including Alzheimer’s Disease (AD). Cause, consequence, and (patho)physiological mechanisms of TAU sorting and missorting are understudied, in part also due to the lack of readily available human neuronal model systems. The human neuroblastoma cell line SH-SY5Y is widely used for studying TAU physiology and TAU-related pathology in AD and related tauopathies. SH-SY5Y cells can be differentiated into neuron-like cells (SH-SY5Y-derived neurons) using various substances. This review evaluates whether SH-SY5Y-derived neurons are a suitable model for i) investigating intracellular TAU sorting in general, and ii) with respect to neuron subtype-specific TAU vulnerability. I) SH-SY5Y-derived neurons show pronounced axodendritic polarity, high levels of axonally localized TAU protein, expression of all six major human brain isoforms, and TAU phosphorylation similar to the human brain. As proliferative cells, SH-SY5Y cells are readily accessible for genetic engineering, stable transgene integration and leading-edge genome editing are valuable and promising tools for TAU-related studies. II) Depending on the used differentiation procedure, SH-SY5Y-derived neurons resemble cells of distinct subcortical nuclei, i.e. the Locus coeruleus (LC), Nucleus basalis (NB) and Substantia nigra (SN), all of which early affected in many tauopathies. This allows to analyse neuron-specific TAU isoform expression and intracellular localization, also in the context of vulnerability to TAU pathology. Limitations are e.g. the lack of mimicking age-related tauopathy risk factors and the difficulty to define the exact neuronal subtype of SH-SY5Y-derived neurons. In brief, this review discusses the suitability of SH-SY5Y-derived neurons for investigating TAU (mis)sorting mechanisms and neuron-specific TAU vulnerability in disease paradigms.

Background: Coronavirus disease 2019 (COVID-19) has emerged as a global threat to human health and disease risk increases with advancing age. The regulation of the ACE2 gene that codes for COVID-19 host receptor ACE2 has been shown to be under epigenetic regulation. Here, we examined whether intensive DNA methylation profiling of the ACE2 gene differed by human host tissue and cell type, gender, and age. Results: Accessing four public datasets, we observed unique human cell-type-specific ACE2 DNA methylation patterns. In human lung tissues, gender differences in DNA methylation at 2 sites related to the ACE2 gene were identified. Further, in freshly isolated airway epithelial cells, DNA methylation near the transcription start site of the ACE2 gene associated with biological age. Conclusion: Epigenetic profiling of host tissue may permit discovery of age and gender-related potential risk factors for COVID-19. How perturbations in ACE2 methylation relate to clinical severity across the ages and gender needs to be determined to guide screening tools and potential epigenetic modification targeting to alleviate COVID-19 morbidity in the elderly.

Data on the seasonally dry tropical forests of Mexico have been examined in the light of statistical mechanics. The results suggest a division into two classes of species. There are drifting populations of a cosmopolitan class capable of existing in most dry forest sites; these have a statistical distribution previously only observed (globally) for populations of alien species. A high proportion of species found only at a single site are endemic and these prefer sites comparatively low in species richness.

An SIRS (Susceptible–Infected–Removed-Susceptible) mathematical model for the transmission dynamics of the Transfusion–Transmitted Malaria (TTM) model with optimal control pair u₁(t) and u₂(t) was developed and studied in this research work. The model Transfusion–Transmitted Malaria disease–free equilibrium and endemic equilibriums points were determined. The model exhibited two equilibriums; disease-free and endemic equilibrium. It is shown that the disease–free equilibrium was locally asymptotically stable if the associated basic reproduction numbers R₀ is less than unity while the disease persists if R₀ is greater than unity. The global stability of the Transfusion–Transmitted Malaria model at the disease-free equilibrium was established using the comparison method. The optimality system was derived and an optimal control model of blood screening and drug treatment for the Transfusion–Transmitted Malaria model was investigated. Conditions for the optimal control were considered using Pontryagin’s Maximum Principle and solved numerically using the Forward and Backward Finite Difference Method (FBDM). Numerical results obtained are in perfect agreement with our analytical results.

Malaria and Pneumonia are leading causes of serious illness in children and adults worldwide with their death rate and prevalence on the rise. Such alarming statistics may retard the milestones so far achieved in meeting the Millennium Development Goals 4 and 6 whose targets are to improve child survival and reverse the high prevalence of diseases such as pneumonia and malaria respectively. Two sub-models of malaria-pneumonia co-infection namely malaria model and pneumonia model were considered first and then followed by the full malaria-pneumonia co-infection model. The malaria model, pneumonia model and co-infection model basic reproduction numbers denoted by R_m, R_p and R_mp respectively was obtained using the Next Generation Matrix method. The model disease free equilibrium’s local and global stability was analysed using Descartes’ Rule of signs and Comparison method. The bifurcation analysis for the malaria, pneumonia and co-infection models was studied using the Centre Manifold Theory. The sensitivity indices of the model basic reproduction numbers R_m, R_p and R_mp to the parameters in the models were calculated. Optimal control theory was applied using the Pontryagins’ Maximum Principle to investigate optimal strategies for controlling the spread of malaria, pneumonia and co-infection models using insecticide treated bed nets (u₁(t)) spraying of mosquitoes insecticides (u₂(t)), sanitation (u₃(t)), vaccination (u₄(t)), anti-malaria drugs (u₅(t)), anti-pneumonia drugs (u₆(t)), both anti-malaria drugs and anti-pneumonia drugs (u₇(t)) as the system time control variables. Numerical simulations using a set of parameter values were provided to validate the analytical results.

This article discusses the results of a series of experiments on pulse ultrasonic cure monitoring of carbon fiber reinforced plastics applied to the pultrusion process. The aim of this study is to validate the hypothesis that pulse ultrasonic cure monitoring can be applied a) for profiles having small cross sections such as 7x0.5 mm and b) within the environment of the pultrusion process. Ultrasonic transducers are adhesively bonded to the pultrusion tool as actuators and sensors. The time-of-flight and the amplitude of an ultrasonic wave are analyzed to deduce the current curing state of the epoxy matrix. The experimental results show that ultrasonic cure monitoring is indeed applicable even to very thin cross sections. However, significant challenges can be reported when the techniques are used during the pultrusion process.

Many species of plants are found in regions to which they are alien. Their global distributions are characterised by a family of exponential functions of the kind that arise in elementary statistical mechanics (an example in ecology is MacArthur's broken stick). We show here that all these functions are quantitatively reproduced by a model containing a single parameter – some global resource partitioned at random on the two axes of species number and site number. A dynamical model generating this equilibrium is a two fold stochastic process and suggests a curious and interesting biological interpretation in terms of niche structures fluctuating with time and productivity; with sites and species highly idiosyncratic. Idiosyncrasy implies that attempts to identify a priori those species likely to become naturalized are unlikely to be successful. Although this paper is primarily concerned with a particular problem in population biology, the two fold stochastic process may be of more general interest.

With an ever broadening use of composite materials manufacturers are in high demand of efficient curing cycles to reduce costs and speed up production cycles. One method to to archive this goal is active cure monitoring to determine the exact time of curing needed. This article provides a novel method to measure the cure inside of closed tools by using ultrasonic spectroscopy. For this a simple experiment is used to show the change of the ultrasonic spectrum during the cure of an epoxy. The results clearly show a direct correlation of amplitude and state of cure where the amplitude reaches a global minimum at the glass point.

Plant growth-promoting rhizobacteria (PGPR) are members of the plant rhizomicrobiome that enhance plant growth and stress resistance by increasing nutrient availability to the plant, producing phytohormones or other secondary metabolites, stimulating plant defense responses against abiotic stresses and pathogens, or fixing nitrogen. The use of PGPR to increase crop yield with minimal environmental impact is a sustainable and readily applicable replacement for a portion of chemical fertilizer and pesticides required for the growth of high-yielding varieties. Increased plant health and productivity have long been gained by applying PGPR as commercial inoculants to crops, although with uneven results. The establishment of plant-PGPR relationships requires the exchange of chemical signals and nutrients between the partners, and polyamines (PAs) are an important class of compounds that act as physiological effectors and signal molecules in plant-microbe interactions. In this review we focus on the role of PAs in interactions between PGPR and plants. We describe the basic ecology of PGPR and production and function of PAs in them and in the plants with which they interact. We examine the metabolism and the roles of PAs in PGPR and plants individually and during their interaction with one another. Lastly, we describe some directions for future research.

As shown previously, a relation between the superconducting transition temperature and some characteristic distance in the crystal lattice holds, which enables the calculation of the superconducting transition temperature, Tc, based only on the knowledge of the electronic configuration and of some details of the crystallographic structure. This relation was found to apply for a large number of superconductors, including the high-temperature superconductors, the iron-based materials, alkali fullerides, metallic alloys, and element superconductors. When applying this scheme called Roeser-Huber formula to Moiré-type superconductivity, i.e., magic-angle twisted bi-layer graphene (tBLG) and bi-layer WSe2, we find that the calculated transition temperatures for tBLG are always higher than the available experimental data, e.g., for the magic angle 1.1∘, we find Tc≈ 4.2–6.7 K. Now, the question arises why the calculation produces larger Tc’s. Two possible scenarios may answer this question: (1) The given problem for experimentalists is the fact that for electric measurements always substrates/caps are required to arrange the electric contacts. When now discussing superconductivity in atomically thin objects, also these layers may play a role forming the Moiré patterns. The consequence of such substrate-induced super-Moiré patterns is that the resulting Moiré pattern always will show a larger cell size, and thus, a lower Tc of the final structure will result. (2) A correction factor to the Roeser-Huber formalism may be required to account for the low charge carrier density of the tBLG. Here, we test both scenarios and find that the introduction of a correction factor η enables a proper calculation of Tc, reproducing the experimental data. We find that η depends exponentially on the value of Tc.

As shown previously, a relation between the superconducting transition temperature and some characteristic distance in the crystal lattice holds, which enables the calculation of the superconducting transition temperature, Tc, based only on the knowledge of the electronic configuration and of some details of the crystallographic structure. This relation was found to apply for a large number of superconductors, including the high-temperature superconductors, the iron-based materials, alkali fullerides, metallic alloys, and element superconductors. When applying this scheme called Roeser-Huber formula to Moiré-type superconductivity, i.e., magic-angle twisted bi-layer graphene (tBLG) and bi-layer WSe2, we find that the calculated transition temperatures for tBLG are always higher than the available experimental data, e.g., for the magic angle 1.1∘, we find Tc≈ 4.2–6.7 K. Now, the question arises why the calculation produces larger Tc’s. Two possible scenarios may answer this question: (1) The given problem for experimentalists is the fact that for electric measurements always substrates/caps are required to arrange the electric contacts. When now discussing superconductivity in atomically thin objects, also these layers may play a role forming the Moiré patterns. The consequence of such substrate-induced super-Moiré patterns is that the resulting Moiré pattern always will show a larger cell size, and thus, a lower Tc of the final structure will result. (2) A correction factor to the Roeser-Huber formalism may be required to account for the low charge carrier density of the tBLG. Here, we test both scenarios and find that the introduction of a correction factor η enables a proper calculation of Tc, reproducing the experimental data. We find that η depends exponentially on the value of Tc.

Electrifying off-grid and isolated islands in the Philippines remains one of the challenges that hinders community development. One of the solutions seen to ensure energy security, expand energy access and promote a low carbon future in this isolated islands is the use of renewable energy sources. This study wishes to determine the nearshore wave energy resource during monsoon seasons in Cuyo Island using a 40-year wave hindcast and 9-year on-site wind speed data to develop high resolution wave energy model using SWAN wave model, and assessed its annual energy production through matching with wave energy devices. Results shows that average significant wave height (Hs), peak period (Tp) and wave power density (Pd) during northeast monsoon are Hs = 1.35 m, Tp = 4.79 s and Pd = 4.05 kW/m respectively, while southwest monsoon which is sheltered by the mainland resulted to a lesser outcome, Hs = 0.52 m, Tp = 3.37 s and Pd = 0.34 kW/m. While the simulated model was observed to overestimate the wave energy resource (Bias = 0.398, RMSE = 0.54 and SI = 1.34), it has a strong relationship with the observed values (average r = 0.9). Its annual energy production is highest at Station 5, with AEPWaveBouy = 43.761 MWh, AEP-Pelamis = 216.786 MWh and AEPWave Dragon = 2462.66 MWh. At present, the minimum requirement for a wave energy development to be feasible is 5 kW/m, which in this case, Cuyo Island falls short, but with the continuous evolution of wave energy converters, applications on milder re-sources will soon materialized.

Respiratory allergic diseases, affect over 500 million people globally and pose a substantial burden in terms of morbidity, mortality, and healthcare costs. Restrictive factors such as geographical disparities, infectious pandemics, limitations in resource, and shortage of allergy specialists in underserved areas, impede effective management. Moreover, the well-established suboptimal adherence in patients with respiratory allergies, contribute further to the accelerated loss of disease control. Telemedicine encompasses real-time visits, store-and-forward options triage, and computer-based technologies for establishing and efficient doctor-patient communication. Recent advances in digital technology, including designated applications, informative materials, digital examination devices, wearables, digital inhalers, and integrated platforms, facilitate personalized and evidence-based care delivery. The integration of telemonitoring in respiratory allergy care has shown beneficial effects in disease control, adherence, and quality of life. While the COVID-19 pandemic accelerated the adoption of telemedicine, certain concerns regarding technical requirements, platform quality, safety, reimbursement, and regulatory considerations remain unresolved. Challenges in telemonitoring implementation further include ensuring effective doctor-patient collaboration, addressing privacy concerns, and establishing cost-effective models. The integration of artificial intelligence (AI) in telemonitoring applications holds promise for data analysis, pattern recognition, and personalized treatment plans. Striking the balance between AI-enabled insights and human expertise is crucial for optimizing the benefits of telemonitoring. This overview reports the up- to- date telemedicine approaches in managing patients with respiratory allergies. While telemonitoring exhibits potential in enhancing patient care and healthcare delivery, critical considerations have to be addressed in order to ensure the successful integration of telemonitoring into the healthcare landscape.

The development of CRISPR associated proteins, such as Cas9, has led to increased accessibility and ease of use in genome editing. However, additional tools are needed to quantify and identify successful genome editing events in living animals. We developed a method to rapidly and quantitatively monitor gene editing activity non-invasively in living animals that also facilitates confocal microscopy and nucleotide level analyses at the end of study. Here we report a new CRISPR “footprinting” approach to activate luciferase and fluorescent proteins in mice as a function of gene editing. This system is based on experience with our prior Cre-detector system and is designed for Cas editors able to target LoxP including gRNAs including SaCas9 and ErCas12a [1, 2]. These CRISPRs cut specifically within LoxP, an approach that is a departure from previous gene editing in vivo activity detection techniques that targeted adjacent stop sequences. In this sensor paradigm, CRISPR activity was monitored non-invasively in living Cre reporter mice (FVB.129S6(B6)-Gt(ROSA)26Sortm1(Luc)Kael/J and Gt(ROSA)26Sortm4(ACTB-tdTomato,-EGFP)Luo/J, which will be referred to as LSL and mT/mG throughout the paper) after intramuscular or intravenous hydrodynamic plasmid injections, demonstrating utility in two diverse organ systems. The same genome-editing event was examined at the cellular level in specific tissues by confocal microscopy to determine the identity and frequency of successfully genome-edited cells. Further, SaCas9 induced targeted editing at efficiencies that were comparable to Cre recombinase demonstrating high effective delivery and activity in a whole animal. This work establishes genome editing tools and models to track CRISPR editing in vivo non-invasively and to fingerprint the identity of targeted cells. This approach also enables similar utility for any of the thousands of previously generated LoxP animal models.

The health of urban citizens is defined by how their living environments are planned, built, and operated. These complex relations between health and the characteristics of built environments require system-orientated thinking and transdisciplinary interventions, yet have mainly been addressed using conventionally narrow sector-based approaches. This paper investigates the opportunities and challenges of the Vietnamese Green Building Movement (GBM) based on a transdisciplinary approach, with attention to additional health benefits of green buildings that are currently under-researched, while highlighting building users’ perspectives. Focusing on the perspectives of high-rise building residents, the paper examines transdisciplinary insights collected from six thematic webinars, expert interviews, and, in particular, from a household survey conducted in Ho Chi Minh City, Vietnam. Among other findings on opportunities and challenges for the Vietnamese GBM, the paper points out a challenging mismatch between the high importance homebuyers place on green building health benefits, and the focus of GBM stakeholders on GB energy-saving benefits- which are not necessarily homebuyers’ most pressing concerns. With this evidence-based inquiry, the paper concludes that improved health and well-being should be considered co-benefits of green buildings, along with energy efficiency. Importantly, this paper also brings attention to the necessity of a systemic and transdisciplinary approach in both academic and practical efforts toward the implementation of SDG3- to “ensure healthy lives and promote wellbeing for all ages”- and SDG 11- “to make cities and human settlements inclusive, safe, resilient and sustainable”.

The phototransduction cascade allows the photoreceptor to avoid saturation and retain the ability to detect light over a very wide range of intensities. The main second messenger of the cascade is cGMP and the main regulatory mechanism is calcium feedback, however some experimental data suggest that cAMP may also be involved in the regulation of the phototransduction cascade. For this to be the case, cAMP would have to change on a time scale of seconds. Currently, there are no data on the dynamics of changes in intracellular cAMP levels on this time scale, largely due to the specificity of the sensory modality of photoreceptors, where it is practically impossible to use conventional experimental approaches based on fluorescence methods. In the present work, we used the method of rapid cryofixation of retinal samples after light stimulation and subsequent isolation of outer segment preparations. Levels of cAMP were measured using highly sensitive metabolomics approaches. PKA activity was also measured in these samples by Western blot. We show that when illuminated with near-saturating but still moderate light, cAMP levels rise transiently within approximately the first second and then return to pre-stimulus levels. The increase in cAMP activates PKA, leading to phosphorylation of PKA-specific substrates in frog retinal outer segments.

The detection of antibiotic-resistant facultative pathogenic bacteria in surface waters is common in the present day. However, there is limited understanding of the factors that influence the spread and stabilization of resistance in this habitat, particularly regarding the role of biofilms. Despite the perceived differences between sediments, biofilms, and open water, their potential contribution to the long-term maintenance of resistances remains unclear. In this study, we investigated Escherichia coli isolates obtained from the Mur and Drava rivers in Austria. Samples were collected from both the water column and sediment at two locations per river: upstream and downstream of an urban area, including a sewage treatment plant. The iso-lates were subjected to antimicrobial susceptibility testing against 21 antibiotics belonging to seven distinct classes. Additionally, any isolates exhibiting an extended-spectrum beta-lactamase (ESBL) or carbapenemase phenotype were further analyzed for the presence of specific antimi-crobial resistance genes. E. coli isolates obtained from the two rivers exhibited resistance to at least one of the tested anti-biotics, with rates of 25.83% and 23.66% respectively. The most prevalent antimicrobial re-sistances observed were towards ampicillin, amoxicillin-clavulanic acid, tetracycline, and na-lidixic acid. Surprisingly, there was a similar proportion of resistant bacteria observed in both open water and sediment samples, contrary to expectations. The difference in resistance levels between samples collected upstream and downstream of the cities was minimal. Out of the total isolates, 13 E. coli were found to carry ESBL genes with one isolate carrying the gene for KPC-2 carbapenemase. There were no significant differences between the biofilm (sediment) and open water samples in the occurrence of antimicrobial resistance. Even the difference between the samples upstream and downstream of the cities and their wastewater treatment plants was minor. There seems to be no evidence of a large adaptive effect in this analysed biofilm population of E. coli. The un-typical phenotype of the KPC-producing and some of the ESBL-producing E. coli from this study could, however, be an indication that such adaptation effects generally exist in water.

Population genetic data underpin many studies of behavioral, ecological, and evolutionary processes in wild populations and contribute to effective conservation management. However, collecting genetic samples can be challenging when working with endangered, invasive, or cryptic species. Environmental DNA (eDNA) offers a way to sample genetic material non-invasively without requiring visual observation. While eDNA has been trialed extensively as a biodiversity and biosecurity monitoring tool with a strong taxonomic focus, it has yet to be fully explored as a means for obtaining population genetic information. Here, we review current research that employs eDNA approaches for the study of populations. We outline challenges facing eDNA-based population genetic methodologies, and suggest avenues of research for future developments. We advocate that with further optimizations, this emergent field holds great potential as part of the population genetics toolkit.

Financial statement analysis is an analysis that uses analytical procedures to evaluate a company's financial health, risks, performance, and future growth potential. This article aims to find out the application of analysis of financial statements of PT. Astra Internasional, Tbk towards the decision-making of novice investors in the Indonesian capital market. This article is qualitative descriptive with literature studies. The results of this article can be concluded that the analysis of the financial statements of PT. Astra Internasional, Tbk can help novice investors in the Indonesian capital market in making investment decisions.

Scholars and policymakers see sustainability as depending on the interrelationships between the three pillars of the environment, society and the economy. However, it remains less clear how key stakeholders with a responsibility for educating the next generation perceive the concept of sustainability and act accordingly. In order to gain new insights, this research scrutinises participant perceptions on sustainability and climate change in two eco-schools in England for primary children (aged 5-11 years). Our case study involved individual interviews with classroom teachers and headteachers, group interviews with fourth- and fifth-year students (ages 10-12 years), and in-class observations. We also analysed data from student exercise books and photographs of school grounds to understand participants’ self-reported knowledge and perceptions of sustainability and climate change. Within a framework drawing on theories of science communication and transformative learning (a learning approach based on having challenging experiences), the results show that the integration of sustainability into the curriculum was limited and problematic. That is despite the fact that all students and teachers were aware of the environmental dimensions of sustainability, like climate change and the overuse of natural sources. These findings suggest that schools are no different to other institutional settings when it comes to dealing with the challenges of integrating sustainability into daily practice. We conclude that there is a need for in-service teacher education programmes to enable and motivate teachers to provide richer teaching-learning environments so as to enable effective learning in schools about sustainability and climate change.

This paper discusses how Marsascala, a coastal town in Malta, has been urbanized over the years, with particular attention to the development of the tourist industry. In this regard, Bruce Young’s (1983) “general model of the process of ‘touristization’ and landscape change” is engaged with in conjunction with other conceptualisations of tourism and urban development. This paper contributes to the following sustainable development goals respectively, 3 (Good Health and Wellbeing); 8 (Decent Work and Economic Growth); 11 (Sustainable Cities and Communities); 14 (Life Below Water); and 15 (Life on Land), in particular with respect to quality of life, urbanization and respective social, environmental, and economic impacts, and through respective recommendations for a sustainable tourism in Marsascala and similar localities.

The ferrocell is an optical viewing device that interacts with a magnetic field and one or more light sources to produce a real-time visual light display. Although this device has been extensively studied by several researchers, a proper computer simulation replicating this optical effect has not yet been presented. Using numerical methods and the law of reflection, a computer simulation was developed that shows that the light patterns as seen in the ferrocell are primarily caused by light reflections off the ferrofluid nano-particles that self organize into needle-like filaments and align along magnetic flux lines in the presence of a magnetic field.

Inhalation of gasoline vapors (GV) is associated with developing various pathologies. Particularly, oil refinery and gas station workers are at greater risk of developing lung cancer, kidney cancer, bladder cancer, and hematological disorders, including acute myeloid leukemia. Therefore, preventing the harmful effects of GV and alleviating their consequences appear to be an important and timely issue. In this study, we investigated the potential of vitamin D3, turmeric powder and their combination to ameliorate the toxicity of gasoline fumes in rats. Separate groups of animals fed with a standard rodent diet, with or without supplementation of vitamin D3 (750 IU/kg of body weight) and/or turmeric powder (0.5%, w/w, in food), were untreated or treated with GV (11.5±1.3 cm3/h/m3/day) for 30, 60 or 90 days. Changes in the body weight were monitored weekly. Histological, biochemical, and hematological parameters were determined at the end of each treatment period. While exposure of rats to GV resulted in a time-dependent reduction in body weight, supplementation with vitamin D3, but not with turmeric root powder or their combination, partially prevented weight loss. Macroscopical and histological analyses showed pronounced time-dependent changes in the organs and tissues of GV-treated rats. These included alveolar wall collapse in the lungs, destruction of the lobular structure and hepato-cytolysis in the liver, shrinkage and fragmentation of glomeruli in the kidneys, and disorganization of the lymphoid follicles in the spleen. However, co-treatment with the nutritional supplements tested, especially vitamin D3, noticeably alleviated the above conditions. This was accompanied by a significant improvement in blood chemistry and hematological parameters. Collectively, our results demonstrate that the harmful effects of environmental exposure to GV can be reduced upon supplementation of vitamin D3. The fact that the protective activity of vitamin D3 alone was higher than that of turmeric root powder or the combined treatment suggests that combinations of these supplements may not always be more beneficial than each agent applied separately.

Veganism and the interest towards a plant-based diet are experiencing exponential growth worldwide, and in Italy more and more individuals and families are adopting this lifestyle and diet, too.Such a change in eating habits also imperatively implies the support and expertise of medical and health care professionals, who to date are still often unprepared and skeptical about this dietary pattern, despite scientific evidence.

The binding of actinide ions (Am(III) and U(VI)) in aqueous solutions by hybrid silica-hyperbranched poly(ethylene imine) nanoparticles (NP) and xerogels (XG) has been studied by means of batch experiments at different pH values (4, 7 and 9) under ambient atmospheric conditions. Both materials present relatively high removal efficiency at pH 4 and pH 7 (> 70%) for Am(III) and U(VI). The lower removal efficiency for the nanoparticles is basically associated with the compact structure of the nanoparticles and the lower permeability and access to active amine groups compared to xerogels, and the negative charge of the radionuclide species formed under alkaline conditions (e.g. UO2(CO3)34- and Am(CO3)2-). Generally, the adsorption process is relatively slow due to the very low radionuclide concentrations used in the study and is basically governed by the actinide diffusion from the aqueous phase to the solid surface. On the other hand, the adsorption is favored with increasing temperature assuming that the reaction is endothermic and entropy-driven, which is associated with increasing randomness at the solid-liquid interphase upon actinide adsorption. To the best of our knowledge, this is the first study on hybrid silica-hyperbranched poly(ethylene imine) nanoparticle and xerogel materials used as adsorbents for americium and uranium at ultra-trace levels. Compared to other adsorbent materials used for binding americium and uranium ions, both materials show far higher binding efficiency. Xerogels could remove both actinides even from seawater by almost 90%, whereas nanoparticles could remove uranium by 80% and americium by 70%. The above, along with their simple derivatization to increase the selectivity towards a specific radionuclide and their easy processing to be included in separation technologies, could make these materials attractive candidates for the treatment of radionuclide/actinide contaminated water.

The creep response of commercially pure titanium was investigated in air at 550, 600 and 650°C, to assess the effect of oxidation on the mechanical response. Experiments demonstrated that exposure at high temperature produced a marked reduction of the minimum creep rate under a given applied stress. Microhardness measurements showed that a hardened zone forms in proximity of the surface, due to oxygen penetration into metal. A simplified composite-model was then used to describe the creep response. In this model, the sample consisted of two zones, the hard case, enriched in oxygen, and the soft pure-titanium core, both creeping with similar strain rates. Calculation led to an estimation of the dependence of the minimum creep rate on stress and temperature for the hard high-oxygen zone. The simplified composite-model here presented gave an excellent description of experimental creep data for pure titanium tested in air and also provided a reliable picture of the effect of oxidation on complex Ti-alloys.

The use of isolated supplements to enhance performance is widespread among athletes. The aim of this study was to increase knowledge about the combined effects of caffeine and New Zealand blackcurrant (NZBC) dietary supplements. In this study, two subjects each underwent four phases of four sessions in a double-blind and randomized alternating treatment single-case design. After a 3-week pre-test phase, the supplement combinations of placebo/placebo, caffeine/placebo (5 mg/kg), NZBC/placebo (600 mg), and caffeine/NZBC (5 mg/kg + 600 mg) were taken and weekly performance tests were conducted to examine their effects on relative power (W/kg) during a 20-minute time trial on a bicycle. Data were analyzed descriptively and using the Tau-U calculator from Single Case Research. The ergogenic effect of caffeine was confirmed in both subjects, with increases of 3.3% and 6.5%, while the positive effect of NZBC on performance was only seen in one subject (13.4%). The combination of caffeine and NZBC again increased performance in both subjects (2.2% and 19.2%), but the data only showed an additive effect of the supplements in one subject. Further studies are required to confirm or refute this evidence of the synergistic effects of these supplements.

The calculation of moments of area is one of the most fundamental aspects of engineering mechanics for calculating the properties of beams or for the determination of invariants in different kind of geometries. While a variety of shapes such as circles, rectangles, ellipses or their combinations can be described symbolically, such symbolic expressions are missing for freeform cross-sections. In particular, periodic B-spline cross-sections are suitable for an alternative beam cross-section, e.g. for the representation of topology optimization results. In this work, therefore, a symbolic description of the moments of area of various parametric representations of such B-splines is computed. The expressions found are then compared with alternative computational methods and checked for validity. The resulting equations show a simple way for fast conceptual computation of such moments of area of periodic B-splines.

All living cells maintain a charge distribution across their cell membrane (membrane potential) by carefully controlled ion fluxes. These bioelectric signals regulate cell behavior (such as migration, proliferation, differentiation) as well as higher-level tissue and organ patterning. Thus, voltage gradients represent an important parameter for diagnostics as well as a promising target for therapeutic interventions in birth defects, injury, and cancer. However, despite much progress in cell and molecular biology, little is known about bioelectric states in human stem cells. Here, we present simple methods to simultaneously track ion dynamics, membrane voltage, cell morphology, and cell activity (pH and ROS), using fluorescent reporter dyes in living human neurons derived from induced neural stem cells (hiNSC). We developed and tested functional protocols for manipulating ion fluxes, membrane potential, and cell activity, and tracking neural responses to wounding and re-innervation in vitro. Finally, using morphology sensor, we tested and quantified the ability of physiological actuators (neurotransmitters and pH) to manipulate nerve wound re-innervation. These methods are not specific to a particular cell type and should be broadly applicable to the study of bioelectrical controls across a wide range of combinations of models and endpoints.

Recent times have witnessed an increasing number of countries and private firms pledging carbon neutrality by mid-century. Whilst representing a significant improvement in intentions to tackle climate change, such pledges lack substance and structure. For instance, individual pledges lack coordination and aggregation among peers, while strategies and measures to achieve ambitious targets are largely absent. Moreover, current disagreements obstructing progress in international climate change negotiations further undermine the reliability of carbon neutrality objectives. Effective international policies are needed to foster aggregate mitigation ambitions and the creation of adequate supporting mechanisms. This theoretical paper describes a governance innovation aimed at overcoming such shortfalls and disagreements through a unifying yet customizable pathway towards carbon neutrality. It does so by first outlining a political governance framework based on a climate club interpretation of Article 6 of the Paris Agreement. Secondly, it proposes carbon emission mitigation effort sharing on a per capita basis to ensure efficiency, equity and political feasibility. Thirdly, this paper describes how the supply of certified mitigations of carbon emissions required to satisfy effort sharing-based demand can be assetized as carbon credits by operationalizing Article 6 as a joint certification mechanism. The resulting governance architecture for managing demand and supply of mitigations shifts efforts to tackle climate change from a ‘problem-driven’ cost approach to ‘opportunity-driven’ value creation pathways towards carbon neutrality.

PG9, PG16, PGT121, and PGT145 antibodies were identified from culture media of activated memory B-cells of an infected donor and shown to neutralize many HIV-1 strains. Since HIV-1 spreads via both free virions and cell-cell fusion, we examined the effect of the antibodies on HIV-1 Env-mediated cell-cell fusion. Clone69TRevEnv cells that express Env in the absence of tetracycline were labeled with Calcein-AM Green, and incubated with CD4+ SupT1 cells labeled with CellTrace™ Calcein Red-Orange, with or without antibodies. Monoclonal antibodies PG9, PG16, 2G12, PGT121, and PGT145 (at up to 50 µg/mL) had little or no inhibitory effect on fusion between HIV-Env and SupT1 cells. By contrast, Hippeastrum hybrid agglutinin completely inhibited fusion. Our results indicate that transmission of the virus or viral genetic material would not be inhibited by these broadly neutralizing antibodies. Thus, antibodies generated by HIV-1 vaccines should be screened for their inhibitory effect on Env-mediated cell-cell fusion.

Peer-to-peer (P2P) energy trading is a new data-driven business model currently being trialed within the energy sector. Introducing P2P transactions to an essential service such as energy could have far-reaching implications for individuals and the grid. This paper raises considerations and questions from social, economic/markets and regulatory points of view, that should be understood and addressed by societies and policymakers. It does this by considering under what circumstances it is reasonable to conceptualize P2P energy trading as part of the sharing economy, and drawing parallels to the sharing economy experience in other sectors. In order to reap the full societal benefits, while avoiding considerable risks to infrastructure and individuals, a policy approach promoting dialogue and innovation is necessary. We suggest the regulatory sandbox is the most appropriate tool to achieve this and would help avoid the breakdown of trust between policymakers and platform companies observed in other sectors.

Long-term continuous time series of SO2 emissions are considered critical elements of both volcano monitoring and basic research into processes within magmatic systems. One highly successful framework for computing these fluxes involves reconstructing a representative time-averaged SO2 plume from which to estimate the SO2 source flux. Previous methods within this framework have used ancillary wind datasets from reanalysis or numerical weather prediction (NWP) to construct the mean plume and then again as a constrained parameter in the fitting. Additionally, traditional SO2 datasets from ultraviolet (UV) sensors lack altitude information which must be assumed to correctly calibrate the SO2 data and to capture the appropriate NWP wind level which can be a significant source of error. We have made novel modifications to this framework which do not rely on prior knowledge of the winds and therefore do not inherit errors associated with NWP winds. To perform the plume rotation, we modify a rudimentary computer vision algorithm designed for object detection in medical imaging to detect plume-like objects in gridded SO2 data. We then fit a solution to the general time-averaged dispersion of SO2 from a point source. We demonstrate these techniques using SO2 data generated by a newly developed probabilistic layer height and column loading algorithm designed for the Cross-track Infrared Sounder (CrIS), a hyperspectral infrared sensor aboard the Joint Polar Satellite System’s Suomi-NPP and NOAA-20 satellites. This SO2 data source is best suited to flux estimates at high-latitude volcanoes and at low-latitude, but high-altitude volcanoes. Of particular importance, IR SO2 data can fill an important data gap in the UV-based record: estimating SO2 emissions from high-latitude volcanoes through the polar winters when there is insufficient solar backscatter for UV sensors to be used.

Annotating training data is a time consuming and labor intensive process in deep learning, especially for images with many objects present. In this paper, we propose a method to allow deep networks to be trained on data with reduced numbers of annotations (per image) in heatmap regression tasks (e.g. object detection and counting), by applying an asymmetric loss function. In a real scenario, this reduction of annotations can be imposed by the researchers (e.g. ask the annotators to label only 50% of what they see in each image), or can potentially counteract unintentionally missing labels from the annotators. To demonstrate the effectiveness of our method, we conduct experiments in two domains, crowd counting and wheat spikelet detection, using different deep network architecture. We drop various percentages of instance annotations per image in training. Results show that an asymmetric loss function is effective across different models and datasets, even in very extreme cases with limited annotations provided (e.g. 90% of the original annotations reduced). Whilst tuning of the key parameters are required, we find that setting conservative parameter values can help more realistic situations, where only small amounts of data have been missed by annotators.

Li-ion battery packs are the heart of modern electric vehicles. Due to their perishable nature, it is crucial to supervise them closely. In addition to on-board supervision over safety and range, insights into the battery’s degradation are also becoming increasingly important, not only for the vehicle manufacturers but also for vehicle users. The concept of digital twins has already emerged on the field of automotive technology, and can also help to digitalize the vehicle’s battery. In this work, we set up a data pipeline and digital battery twin to track the battery state, including state of charge (SOC), state of health (Capacity) (SOHc ) and state of health (Resistance) (SOHr ). To achieve this goal, we reverse-engineer the diagnostics interface of a 2014 e-Golf to query for Unified Diagnostic Services (UDS) messages containing both battery pack and cell-individual data. An on-board diagnosis (OBD) logger records the data with edge-processing capability. Pushing this data into the cloud twin system using IoT-technology, we can fit battery models to the data and infer cell individual internal resistance from them. We find that the resistances of the cells differ by a magnitude of two. Furthermore, we propose an architecture for the battery twin in which the twin fleet shares resources like models by encapsulating them in Docker containers run on a cloud stack. By using web technology, we present the analyzed results on a web interface.

The limitedness of the nonrenewable local energy resources in Israel, even in background of the later gas fields’ findings, continues to force the state to devote various efforts for the ‘green’ energy development. These efforts include installations both in the solar and in the wind energy, with a purpose to improve the diversity of energy sources. While the standard discounted cash flow (DCF) method using the net present value (NPV) criterion is extensively adopted to evaluate investments, the standard DCF method is inappropriate for the rapidly changing investment climate and for the managerial flexibility in investment decisions. In recent years, the real options analysis (ROA) technique is widely applied in many studies for valuation of renewable energy investment projects. Hence, we apply in this study the real options analysis approach for the valuation of wind energy turbines and apply it to the analysis of wind energy economic potential in Israel.

The most common type of non-Hodgkin lymphoma in adults is diffuse large B-cell (DLBCL). There is a historical unmet need for more effective therapies in the 2nd and 3rd line setting. Emerging immunochemotherapies have shown activity in small studies of heavily pre-treated patients with prolonged remissions achieved in some patients. Anti-CD19 CAR (chimeric antigen receptor) T cells are potentially curative in the 3rd line and beyond setting and are under investigation in earlier lines of therapy.1 Antibody-drug conjugates (ADC’s) such as polatuzumab vedotin targeting the pan-B-cell marker CD79b has proven effectiveness in multiply-relapsed DLBCL patients. Tafasitamab (MOR208) is an anti-CD19 monoclonal antibody producing prolonged remissions when combined with Lenalidomide in patients who were not candidates for salvage chemotherapy or autologous stem cell transplant. Selinexor, an oral, small-molecule selective inhibitor of XPO1-mediated nuclear export (SINE), demonstrated prolonged activity against heavily-pretreated DLBCL without cumulative toxicity and is being investigated as part of an oral, chemotherapy-free regimen for relapsed aggressive lymphoma. This article reviews current strategies and novel therapies for relapsed/refractory DLBCL.

Background: Social skills deficits are present in 43.3% of major depressed patients and significantly impact health-related quality of life. However, studies concerning social deficits as state-dependent markers of depression are limited. Objective: To delineate the effects of severity of depression, personality characteristics, family support satisfaction and self-esteem on social skills in clinical depression. Methods: We recruited 150 patients with major depressive disorder or persistent depressive disorder and assessed 1) Beck Depression Inventory-II (BDI-II), 2) Social Skill Inventory (SSI), 3) Family Adaptation, Partnership, Growth, Affection, Resolve (APGAR) Questionnaire 4) Rosenberg Self-Esteem Scale (RSES) and 5) Maudsley Personal Inventory (MPI). Results: Social skills deficits were significantly associated with female gender, age < 40 years, depression severity, introvert / neurotic personality, and lowered family support satisfaction and self-esteem. A large part of the variance (47.2%) in social skills deficits was predicted by satisfaction of family support, introvert personality, and low self-esteem. Exploratory Factor Analysis showed that a bifactorial model best fitted the data with a) a general factor loading highly on BDI-II, SSI emotional and social, APGAR, RSES, MPI_introvert and MPI_neurotic scores, and b) a single-group factor loading on both SSI, RSES, and MPI introvert scores. Conclusion: In clinical depression, social skills deficits covary with increasing severity of depression and thus constitute a state marker of depression, and independently from severity of depression covary with introvert personality features. As such, remission of social skills deficits may emerge as a novel objective for the treatment of depression and prevention of new episodes.

Physical-law based models are widely utilized in the aerospace industry. One such use is to provide flight dynamics models for use in flight simulators. For human-in-the-loop use, such simulators must run in real-time. Due to the complex physics of rotorcraft flight, to meet this real-time requirement, simplifications to the underlying physics sometimes have to be applied to the model, leading to model response errors in the predictions compared to the real vehicle. This study investigated whether a machine-learning technique could be employed to provide rotorcraft dynamic response predictions, with the ultimate aim of this model taking over when the physics-based model's accuracy degrades. In the current work, a machine-learning technique was employed to train a model to predict the dynamic response of a rotorcraft. Machine learning was facilitated using a Gaussian Process (GP) non-linear autoregressive model, which predicted the on-axis pitch rate, roll rate, yaw rate and heave responses of a Bo105 rotorcraft. A variational sparse GP model was then developed to reduce the computational cost of implementing the approach on large data sets. It was found that both of the GP models were able to provide accurate on-axis response predictions, particularly when the input contained all four control inceptors and one lagged on-axis response term. The predictions made showed improvement compared to a corresponding physics-based model. The reduction of training data to one-third (rotational axes) or one-half (heave axis) resulted in only minor degradation of the GP model predictions.