The World Health Organization (WHO) recently added snakebite envenoming to the priority list of Neglected Tropical Diseases (NTD). It is thought that ~75% of mortality following snakebite occurs outside the hospital setting, making the temporal gap between a bite and antivenom administration a major therapeutic challenge. Small molecule therapeutics (SMTs) have been proposed as potential pre-referral treatments for snakebite to help address this gap. Herein, we discuss the characteristics, potential uses and development of SMTs as potential treatments for snakebite envenomation. We focus on SMTs that are secretory phospholipase A2 (sPLA2) inhibitors and metalloprotease (MP) inhibitors.

In common model testing practise, the measured values of the self propulsion test are split into the characteristics of the hull, the propeller and into the interaction factors. These coefficients are scaled separately to the respective full scale values and subsequently reassembled to give the power prediction. The accuracy of this power prediction depends {\em inter alia} on the accuracy of the measured values and the scaling procedure. An inherent problem of this approach is, that it is virtually impossible to verify each single step, because of the complex nature of the underlying problem. In recent years the scaling of the open-water characteristics of propeller model tests attracted a renewed interest, fuelled by competitive tests, which became the norm due to requests of the customer. This paper will show the influence of different scaling procedures on the predicted power. The prediction is compared to the measured trials data and the quality of the prediction will be judged. The procedures examined are the standard ITTC~1978 procedure plus derivatives of it: the Meyne, the strip method and the βᵢ-method.

With the rise of long-read sequencers and long-range technologies, delivering high-quality plant genome assemblies is no longer reserved to large consortia. Indeed, sequencing techniques but also computer algorithms have reached a point where the reconstruction of assemblies at the chromosome-scale is now feasible at the laboratory scale. Current technologies, and especially long-range technologies, are numerous and selecting the most promising one for the genome of interest is crucial to obtain optimal results. In this study, we resequenced the genome of the yellow sarson, Brassica rapa cv. Z1, using the Oxford Nanopore PromethION sequencer and assembled the sequenced data using current assemblers. To reconstruct complete chromosomes, we used and compared three long-range techniques, optical mapping, Omni-C and Pore-C sequencing libraries commercialized by Bionano Genomics, Dovetail Genomics and Oxford Nanopore Technologies respectively, or a combination of the three, in order to evaluate the capability of each technology.

Context: COVID-19 pandemic and the Lockdown implemented as a measure to contain the virus spread has taken a toll over the psychological well-being of the people especially the young adults, the confinement along with the environment of a highly infectious pandemic around the induvial are put under great stress.Aims: The current study aims to assess the psychological impact and perceived stress due to COVID-19 lockdown in Young Adult population of India.Settings and Design: It is a cross sectional, observational study.Methods and Material: The survey was conducted using Google forms involving snowball sampling technique which obtained 267 responses in total. (IES-R) and (PSS) scales were used for the study.Statistical analysis used: Descriptive analysis were performed on the sociodemographic parameters and the comparison of means were done by Chi-square test in SPSS Statistic 21.0 (IBM SPSS Statistics, New York, United States). Results: The mean IES-R and PSS scores obtained for the population in this study was 25.64±18.95 and 18.27±6.10 respectively. Out of the 267 respondents in total 61.4% (n=164) of them were males. Maximum of the respondents 62.54%(n=167) belonged to the age group of 18-23 with mean age being 23.14± 2.913. 92.5% of the respondents were unmarried and only 26.6% belonged to the rural part of India. Females, younger individuals were found to have higher IES-R and PSS scores. Conclusions: There is significant psychological burden and stress on the young Indian population with females and younger individuals particularly students are the most vulnerable population.

Analyses of the Hubble diagrams are presented for SN1a supernovae and gamma ray bursts in the redshift ranges z = 0.01–1.3 and 0.034–8.1, respectively. Data are presented on the typical z/μ scale and also on the less common yet increasingly sensitive photon flight time t/(z+1) scale. The primary conclusion is that on the basis of the presently accessible data in the redshift range z = 0.01–8.1, the slope of the Hubble diagram is, or is extremely close to, exponential.

Ultra Low Temperature Process (ULTP) involve the material cooling in temperatures close to the liquid nitrogen (-196 °C), which is different from the cold-treatment (CT) made in temperatures close to -80 °C. ULTP treatments could raise the tool steel wear resistance through microstructural change that occurs on the material, enhancing, that way, the tools and dies lifetime. To investigate the impact on the wear resistance of tool steel AISI D2, micro abrasive wear tests were carried out and an analysis based on the Archard’s law was considered, evaluating specimen mass loss by laser interferometry. Micro hardness tests, X-ray diffractometry, scanning and optical microscopy and quantitative evaluation of carbides with image analysis were carried out aiming material characterization. Micro-scale abrasion tests shown a wear coefficient k about 1.73E-7 e 2.61E-7 mm3/N.mm to the specimens that received the ULTP phase and 3.12E-7 mm3/N.mm to the conventional thermal treatment, representing a wear resistance increase of 16.3 – 44.5% to cryogenically treated specimens. The results demonstrated a micro hardness improvement, ranging from 0.9 - 4.7% for the cryogenically treated specimens, when compared to the bulk material. This effect is related, mainly, to the retained austenite transformation in martensite and to the increase in the amount of fine secondary carbides dispersed in the martensitic matrixes of cryogenically treated specimens with ULTP. The best wear resistance improvements, on micro-scale, were achieved when the ULTP step is performed immediately after tempering.

After reviewing foundational literature by Snyder, I will demonstrate how hope theory has been used in psychological interventions and psychiatry, how hope influences learning and medical outcomes, and how hope can be applied to difficult life circumstances. Using this literature review, hope theory will be interrogated. I will argue that hope theory has developed its way through the years to garner many strengths, however a few weaknesses do exist and will be described. I will conclude with recommendations for using hope theory in practice, including the medical field, psychological interventions and counseling, and student development.

There exists an implicit potential limitation in every physical discoveries that has been implemented and understood. However, the limitations can be bounded within a safe limit to prevent any constructing theory to be free from errors. As, it’s the inert nature of the humans, to go far beyond the scope of experimental findings in order to pursue any studies with the sole help of logical reasoning and mathematics, the argument can be prevailed in the form of WEAK Clampdown Effect & STRONG Clampdown Effect. More, the theories are constructed out of physical nature, more the theory gets hypothetical without any finding evidence, but that does or doesn’t actually justify the phenomenon, that too with the more increment of KARDASHEV Scale, more moderate ways of experimentation got developed curbing down the limitations within the human limit of ‘ERRORS’, that does can be neglected by approximation. Relationship being cross-judgmental on the basis of the computational limits and calculation accuracy, leading to a soft singularity, as a warning, that if computer powers cannot be checked on the basis of error approximations, then this may lead to the hitting of a hard singularity, that in phase with the forbidden gap (or after the optimum limit that arises at the core constraints of nature) to prevent the computation being carried off with respect to super-intelligence machines that are cognitive capability oriented future computers responsible for self growth & reproduction with more improvement algorithm, restricting all forms of humanity & constraints the human growth by virtue of limiting capacities of the humans as compared to computers.

The glycosaminoglycan, heparan sulphate (HS), orchestrates many developmental processes. Yet its biological role has not yet fully been elucidated. Small molecule chemical inhibitors can be used to perturb HS function and these compounds pro-vide cheap alternatives to genetic manipulation methods. However, existing chemical inhibition methods for HS also interfere with chondroitin sulphate (CS), complicating data interpretation of HS function. Herein, a simple method for the selective inhibition of HS biosynthesis is described. Using endogenous metabolic sugar pathways, Ac4GalNAz produces UDP-GlcNAz, which can target HS synthesis. Cell treatment with Ac4GalNAz resulted in defective chain elongation of the polymer and decreased HS expression. Conversely, no adverse effect on CS production was observed. The inhibition was transient and dose-dependent, affording rescue of HS expression after removal of the unnatural azido sugar. The utility of inhibition is demonstrated in cell culture and in whole or-ganisms, demonstrating that this small molecule can be used as a tool for HS inhibition in biological systems.

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

With continued technological innovation in the fields of mixed reality (MR), wearable-type MR devices, such as helmets, have been released and are frequently used in various fields, such as entertainment, training, and education. However, because each product has different parts and specifications in terms of the design and manufacturing process, users feel that the virtual objects overlaying real environments in MR are visualized differently depending on the scale and color used by the MR device. In this paper, we compare the effect of scale and color parameters on users’ perception in using different types of MR devices to improve MR experience. We conducted two experiments (scale and color), and our experimental study showed that the subjects who participated in the scale perception experiment clearly tended to underestimate virtual objects, compared with real objects, and overestimate color in MR environments. [MM1]Please confirm meaning.

The physical and economic sustainability of using Built Environment Wind Turbine (BEWT) systems depends on the wind resource potential of the candidate site. Therefore, it is crucial to carry out a wind resource assessment prior to deployment of the BEWT. The assessment results can be used as a referral tool for predicting the performance and lifespan of the BEWT in the given built environment. To date, there is limited research output on BEWTs in South Africa with available literature showing a bias towards utility-scale or conventional ground based wind energy systems. This study aimed to assess wind power generation potential of BEWT systems in Fort Beaufort using the Weibull distribution function. The results show that Fort Beaufort wind patterns can be classified as fairly good and that BEWTs can best be deployed at 15m for a fairer power output as roof height wind speeds require BEWT of very low cut-in speed of at most1.2ms⁻¹.

Filamentous fungi such as Aspergillus spp. are opportunistic pathogens, which cause highly invasive infections, especially in immunocompromised individuals. Control of such fungal pathogens is increasingly problematic due to the small number of effective drugs available for treatment. Moreover, the increased incidence of fungal resistance to antifungal agents makes this problem a global human health issue. The cell wall integrity system of fungi is the target of antimycotic drugs echinocandins, such as caspofungin (CAS). However, echinocandins cannot completely inhibit the growth of filamentous fungal pathogens, which results in survival/escape of fungi during treatment. Chemosensitization was developed as an alternative intervention strategy, where co-application of CAS with the intervention catalyst octyl gallate (OG; chemosensitizer) greatly enhanced CAS efficacy, thus achieved ≥ 99.9% elimination of filamentous fungi in vitro. Based on hypersensitive responses of Aspergillus antioxidant mutants to OG, it is hypothesized that, besides destabilizing cell wall integrity, the redox-active characteristic of OG may further debilitate fungal antioxidant system.

Given the cross-scale interactions of agricultural ecosystems, it is important to collect ecosystem service data at the multiple spatial scales they operate at. Mapping of ecosystem services helps to assess their spatial and temporal distribution and is a popular communication tool of their availability and value. For example, maps can be used to quantify distance between areas of available ecosystem services and their beneficiaries and how services fluctuate with changes in land use patterns over time, allowing identification of synergies and trade-offs. However, a lack of local context and too large a resolution can reduce the utility of these maps, whilst masking heterogeneities in access due to equity dynamics. This review identifies and summarizes eight main methods of ESS mapping found in the literature—remote sensing, biophysical modelling, agent based modelling, economic valuation, expert opinion, user preference, participatory mapping, and photo-elicitation. We consider what spatial scales these methods are utilized at and the transferability of data created by each method. The analysis concludes with a methodological framework for mapping ecosystem services, intended to help researchers identify appropriate methods for a multi-scale research design. The framework is exemplified with an overview of a research project in Ethiopia.

Skin melanoma presents increasing prevalence and poor outcomes. Progression to aggressive stages is characterized by overexpression of the transcription factor E2F1 and activation of downstream prometastatic gene regulatory networks (GRNs). Appropriate therapeutic manipulation of the E2F1-governed GRNs holds the potential to prevent metastasis however, these networks entail complex feedback and feedforward regulatory motifs among various regulatory layers, which make it difficult to identify druggable components. To this end, computational approaches such as mathematical modeling and virtual screening are important tools to unveil the dynamics of these signaling networks and identify critical components that could be further explored as therapeutic targets. Herein, we integrated a well-established E2F1-mediated epithelial-mesenchymal transition (EMT) map with transcriptomics data from E2F1-expressing melanoma cells to reconstruct a core regulatory network underlying aggressive melanoma. Using logic-based in silico perturbation experiments of a core regulatory network, we identified that simultaneous perturbation of Protein kinase B (AKT1) and oncoprotein murine double minute 2 (MDM2) drastically reduces EMT in melanoma. Using the structures of the two protein signatures, virtual screening strategies were performed with the FDA-approved drug library. Thus, by combining drug repurposing and computer-aided drug design techniques, followed by molecular dynamics simulation analysis identified two potent drugs (Cialis and Finasteride) that can efficiently inhibit AKT1 and MDM2 protein signatures respectively, and with better therapeutic properties. We proposed that these two drugs could be considered for the development of therapeutic strategies for the management of aggressive melanoma.

This study investigated the roles of transactions cost in MSMEs access to finance. This was done by investigating the impact of transactions cost on access to credit from both MSMEs and financial institutions (commercial banks and microfinance banks). From the MSMEs’ side, borrowing experience, decision lag, firm size and borrowers’ distance to the loan office were investigated. On the financial institution’s side, the costs of information gathering, loan administration, monitoring and loan enforcement were investigated. We used the questionnaire survey method, in-depth interviews and case studies, as well as the annual financial statements of the banks. We identified interest rate and collateral value as constraints to access to finance for MSMEs. We also found financial institutions’ attitude to MSMEs access to credit was not friendly. Financial institutions need to do more to bring down transaction cost of lending. This hopefully can be achieved by investing more in agent banking which would lower operating costs, as well as spreading risk, and ultimately increase credit intermediation to small businesses.

Effective biomarkers are essential to the early diagnosis of non-small cell lung cancer (NSCLC). Herein, a retrospective study of 49 newly diagnosed and recurrent NSCLC patients, 31 patients with benign pulmonary disease and 24 healthy volunteers was conducted, to evaluate the diagnostic value of circulating rare cells for NSCLC. The expression of circulating tumor cells (CTCs) and circulating tumor-derived endothelial cells (CTECs) in peripheral blood were measured by subtraction enrichment-immunostaining-fluorescence in situ hybridization (SE-iFISH). The level of CTCs (P＜0.001) and CTECs (P＜0.001) was significantly higher in NSCLC group than that in benign pulmonary disease group. The proportion of small CTCs (P＜0.001) and CTECs (P＜0.0001) significantly increased from benign lung disease individuals to NSCLC patients. The AUC of ROC curves of total CTCs and CTECs were 0.815 (95%CI: 0.722~0.907), 0.739 (95%CI: 0.618~0.860), respectively. The cut-off values for discriminating NSCLC with benign lung disease patients were total CTCs 11.5 units/6ml and total CTECs 10.5 units/6ml, with sensitivity and specificity being 67.3% and 83.9%, 77.6% and 77.4%, respectively. When CTCs and CTECs were combined, predictive value significantly increased to 82.6% as measured by the area under the curve. Small CTCs and triploid CTCs had high positive predictive value (PPV) and positive likelihood ratio (LR+) of the diagnosis of NSCLC in early stage. CTCs and CTECs can not only be used as new biomarkers for the diagnosis of NSCLC, but can also improve diagnostic performance of the early stage NSCLC. Moreover, the combined examination of CTCs and CTECs is be superior to the single.

The ecological background condition of the semi-arid steppe region (SASR) is extremely fragile. It is recognized that the development of coal and electricity power is a kind of strong human interference behavior for regional landscape ecology. Landscape ecological classification (LEC) is the premise of landscape ecology research of the mining area. The current research on the SASR and grassland LEC of coal-power base is relatively less, but still remains uncertainty concerning how to stratify and classify urban mining landscapes into units of ecological significance at spatial scales appropriate for management. This study is based on hierarchy theory, scale theory, landscape process, the patch-corridor-matrix model, the network, the theory of multiple planning integration and the principle of remote sensing. According to the comprehensive principle, principles of the combining of structure and function, principle of the combining human-ominated and natural landscape, principle of emphasis, and principle of combining qualitative analysis with quantitative research of LEC in large-scale coal-power base(LSCPB). On the basis of occurrence method land classification, fully consider the ecological attributes of the land, integration pattern, processes and function theory of the landscape ecology, the LEC system of the LSCPB in the SASR has been constructed by using top-down decomposition classification method. Empirical research of the Victory and Mindong No.1 mining areas of Shenhua Group shows that the classification system constructed in this paper can meet the requirements of LEC and fully reflect the status of landscape ecology of LSCPB in SASR. This study can provide theoretical guidance for the landscape ecology of LSCPB, while also supporting a theoretical reference for the LEC research.

The advent of RNA-sequencing (RNA-Seq) technologies has markedly improved our knowledge and expanded the compendium of small non-coding RNAs, most of which derive from the processing of longer RNA precursors. In this review article, we will discuss about the biogenesis and function of small non-coding RNAs derived from eukaryotic ribosomal RNA (rRNA), called rRNA fragments (rRFs), and their potential role(s) as regulator of gene expression. This relatively new class of ncRNAs remained poorly investigated and underappreciated until recently, due mainly to the a priori exclusion of rRNA sequences—because of their overabundance—from RNA-Seq datasets. The situation surrounding rRFs resembles that of microRNAs (miRNAs), which used to be readily discarded from further analyses, for more than five decades, because we could not believe that RNA of such a short length could bear biological significance. As if we had not yet learned our lesson not to restrain our investigative, scientific mind from challenging widely accepted beliefs or dogmas, and from looking for the hidden treasures in the most unexpected places.

Beta adrenoblockers is a large class of drugs mainly used to manage abnormal heart rhythms. Over the last couples of decades, the anticancer effects of these compounds has been extensively studied. There is much evidence about their activity in non-small cell lung, pancreatic, breast, colorectal, prostate and ovarian cancer. However, the mechanism of beta blockers anticancer activity is still not known, and more detailed studies are needed. The aim of our study was to evaluate the anticancer activity of beta adrenoblockers in non-small cell lung cancer cell lines A549 and H1299. In order to find the relationship with their selectivity to beta adrenoreceptors, in our study we used selective (atenolol, betaxolol, esmolol, metoprolol) and non-selective (pindolol, propranolol and timolol) beta blockers. The effect on cell viability was evaluated by MTT assay and the activity on cell ability to form colonies was tested by clonogenic assay. The type of cell death was evaluated by cell double staining with Hoechst 33342 and Propidium iodide. The most active adrenoblockers against both tested cancer cell lines were propranolol and betaxolol. They completely inhibited lung cancer cell colony formation at 90% of EC50 (half maximal effective concentration) value. Most tested compounds induced cell death through apoptosis and necrosis. In A549 cell lines apoptosis was mainly induced while in H1299 cell line compounds induced both apoptosis and necrosis. There was no correlation established between beta adrenoblocker anticancer activity and their selectivity to beta adrenoreceptors.

Properties of spatially explicit data are often ignored or inadequately handled in machine learning for spatial domains of application. At the same time, resources that would identify these properties and investigate their influence and methods to handle them in machine learning applications are lagging behind. In this survey of the literature, we seek to identify and discuss spatial properties of data that influence the performance of machine learning. We review some of the best practices in handling such properties in spatial domains and discuss their advantages and disadvantages. We recognize two broad strands in this literature. In the first, the properties of spatial data are developed in the spatial observation matrix without amending the substance of the learning algorithm; in the other, spatial data properties are handled in the learning algorithm itself. While the latter have been far less explored, we argue they offer the most promising prospects for the future of spatial machine learning.

Non-coding RNAs (ncRNAs) comprise a diverse class of non-protein coding transcripts that regulate critical cellular processes associated with cancer. Advances in RNA-sequencing (RNA-Seq) have led to the characterization of non-coding RNA expression across different types of human cancers. Through comprehensive RNA-Seq profiling, a growing number of studies demonstrate that ncRNAs, including long non-coding RNA (lncRNAs) and microRNAs (miRNA), play central roles in progenitor B-cell Acute Lymphoblastic Leukemia (B-ALL) pathogenesis. Furthermore, due to their central roles in cellular homeostasis and their potential as biomarkers, the study of ncRNAs continues to provide new insight into the molecular mechanisms of B-ALL. This article reviews the ncRNA signatures reported for all B-ALL subtypes, focusing on technological developments in transcriptome profiling and recently discovered examples of ncRNAs with biologic and therapeutic relevance in B-ALL.

Small boat fishers are often the lifeblood of remote coastal communities in Iceland, contributing to employment, jobs and economic prosperity. This study conducts exploratory but highly practical research into the efficiency of onboard catch handling practices by Icelandic small boat fishers using fish handling tools called automatic jigging machines. Using applied research methods, this study researches whether standardisation of operations could be applied to make catch handling practices on small boats more time and resource efficient, leading to reduced waste, a consistently higher quality product, and potential increases in economic efficiency and sustainability. Thematic analysis, value stream mapping, flow analysis and Kaizen ideology were adopted to identify gaps and continuous improvement opportunities to standardise processes, leading to exemplary performance. Eight core recommendations are identified, seven of which are classed as straight-forward, ‘do now’ measures according to a Kaizen Priority Matrix. These include human and technological interventions in the areas of safety, organisational arrangements, hygiene, fish handling and bleeding, and cooling. Questionnaire responses reveal four main themes of importance to the sub-sector: changes in recent decades; the importance of small boat fishers; education and improvement; and the particularities of the sub-industry. The latter include the perception of a ‘race against time’ to land the catch, an issue that sometimes contributes to sub-optimal catch handling practices. Although this study has decidedly practical connotations for small boat fishers, its outcomes are also likely to be of interest to academics, particularly those focused on the organisational management of natural resources and general applications of the project management methodology and applied research methods as a means of solving practical problems in everyday life.

Medical and translational scientific research requires the use of animal models as an initial approach to the study of new therapies and treatments, but when the objective is an exploration of translational potentialities, classical models fail to adequately mimic problems in humans. Among the larger animal models that have been explored more intensely in recent decades, small ruminants, namely sheep and goats, have emerged as excellent options. The main advantages associated to the use of these animals in research works are related to their anatomy and dimensions very similar to those of humans in most physiological systems, in addition to their low maintenance and feeding costs, tendency to be docile, long life expectancies and few ethical complications raised in society. The most obvious disadvantages are the significant differences in some systems such as the gastrointestinal, and the reduced amount of data that limits the comparison between works and the validation of the characterization essays. Despite everything, recently these species have been increasingly used as animal models for diseases in different systems, and the results obtained open doors for their more frequent and advantageous use in the future. The purpose of this review is to summarize the general principles related to the use of small ruminants as animal models, with focus on regenerative medicine, to group the most relevant works and results published recently and to highlight the potentials for the near future in medical research.

The current SARS-CoV-2 pandemic is still threatening humankind. Despite first successes in vaccine development and approval, no antiviral treatment is available for COVID-19 patients. The success is further tarnished by the emergence and spreading of mutation variants of SARS-CoV-2, for which some vaccines are not effective anymore. This highlights the urgent need for antiviral therapies even more. This article describes how the Genome-Scale Metabolic Model (GEM) of the host-virus interaction of human alveolar macrophages and SARS-CoV-2 was refined by incorporating the latest information about the virus’s structural proteins and the mutant variants B.1.1.7 and B.1.351. We confirmed the initially identified guanylate kinase as a potential antiviral target with this refined model and identified further potential targets from the purine and pyrimidine metabolism. The model was further extended by incorporating the virus’ lipid requirements. This opened new perspectives for potential antiviral targets in the altered lipid metabolism. Especially the phosphatidylcholine biosynthesis seems to play a pivotal role in viral replication. The guanylate kinase is even a robust target in all investigated mutation variants currently spreading worldwide. These new insights can guide laboratory experiments for the validation of identified potential antiviral targets. Only the combination of vaccines and antiviral therapies will effectively defeat this ongoing pandemic.

Membranes based on sulfonated synditoactic polystyrene were thoroughly characterized by contrast variation SANS over a wide Q-range in dry and hydrated states. The film samples were prepared by solid-state sulfonation that allowed a uniform sulfonation of only the amorphous phase while preserving the crystallinity of the membrane. The samples were loaded with different guest molecules in either the amorphous (fullerenes) or the crystalline (toluene) regions, in order to vary the neutron contrast or to reproduce the conditions enabling an increased resistance of the membranes to chemical decomposition. The use of uni-axially deformed film samples and contrast variation with different H2O/D2O mixtures allowed for the identification and characterization of different structural levels with sizes between nm and μm, which form and evolve in the membrane morphology in dry and hydrated states and produce scattering features on different detection sectors and at different detection distances after the sample, depending on their size and orientation.

Risk assessment management have been a hot topic for the researchers since a very long time. Software risk management is an important part of project management as it contains the identification, analysis, estimation and monitoring of different risks present in the system. This helps developers in decision making while assessing the problems that could arise in the software systems. Risk management is very complex in large scale system as these systems have very complex development. The paper describes risk management techniques for large scale system. Furthermore we have provided a detailed comparative analysis of these techniques with commonly identified risks in software systems and have provided a systematic order for risk management process to ensure risk mitigation.

Electric vehicles, being able to reduce pollutant and greenhouse gas emissions and shift the economy away from oil products, can play a major role in the transition towards low-carbon energy systems. However, the related increase in electricity demand inevitably affects the strategic planning of the overall energy system as well as the definition of the optimal power generation mix. With this respect, the impact of electric vehicles may vary significantly depending on the composition of both total primary energy supply and electricity generation. In this study, Italy and Germany are compared to highlight how a similarity in their renewable shares not necessarily leads to a CO₂ emissions reduction. Different energy scenarios are simulated with the help of EnergyPLAN software assuming a progressive increase in renewable energy sources capacity and electric vehicles penetration. Results show that, for the German case, the additional electricity required leads to a reduction in CO₂ emissions only if renewable capacity increases significantly, whereas the Italian energy system benefits from transport electrification even at low renewable capacity. Smart charging strategies are also found to foster renewable integration; however, power curtailments are still significant at high renewable capacity in the absence of large-scale energy storage systems.

Researchers have reported various impacts of the COVID-19 outbreak on small-scale fishers, such as stagnating market demands, reduction of market price and income, etc. While literature have heeded to these impacts in a relatively short time frame, scant evidence exists on the changing impacts over time and on the detailed processes of how fishers have been coping with the challenges in a longer time period. Furthermore, few studies have comprehensively analysed the impacts and strategies from multiple perspectives. This study aims to explore the perceived impacts of the COVID-19 outbreak on small-scale fishing communities and to highlight the coping strategies adopted by fishers over a year since the initial outbreak, through a case study in Trang Province, Thailand. Analysis of both qualitative and quantitative data obtained through semi-structured interviews indicated that fishers wisely utilised natural, financial and social capitals at the early stages of the outbreak, while human capitals were essential for recovering from the impacts in the later stages. Our findings suggest that the adaptive capacity to flexibly change livelihood strategies are crucial, while alternative income source may not necessarily help small-scale fishers under stagnating global economy.

Individuals with low health literacy (HL) are known to have poorer health outcomes and to have higher mortality rates compared to individuals with higher HL: hence, the improvement of HL is a key outcome in modern healthcare systems. Healthcare providers are therefore asked to support patients’ literacy skills by encouraging the implementation of autonomy-supportive patient centered communication (PCC), which in turn requires the enhancement of patient engagement. Our main hypothesis is that the well-known relationship between autonomy-supportive PCC and HL is mediated by patient engagement which is known to play a role in HL promotion and that is related to PCC as well. The purpose of this study was to formulate a hypothetical structural equation model (SEM) linking PCC to patient engagement and HL. A cross-sectional survey design was employed involving 1007 Italian chronic patients. The hypothetical model was tested using SEM to verify the hypothesized mediation of patient engagement between PCC and HL. Results show that the theoretical model has a good fit indexes and that patient engagement fully mediates the relationship between PCC and HL. This finding suggests healthcare systems to implement a new paradigm where patients are supported to play an autonomous role in their own healthcare.

In contrast to normal cells, tumor cells of multiple entities overexpress the Heat Shock Protein 70 (Hsp70) not only in the cytosol, but also present it on their plasma membrane in a tumor-specific manner. Furthermore, membrane-Hsp70 positive tumor cells actively release Hsp70 into lipid microvesicles termed exosomes into the blood. Due to conformational changes of Hsp70 in the lipid environment, most commercially available antibodies fail to detect membrane-bound and exosomal Hsp70. To fill this gap and to assess the role of exosomal Hsp70 in the circulation as a potential tumor biomarker, we established the novel complete Hsp70 (compHsp70) sandwich ELISA using two monoclonal antibodies (mAbs) that are able to recognize both, free and lipid-associated Hsp70 on the cell surface of viable tumor cells and exosomes. The epitopes of the mAbs cmHsp70.1 (aa 451-461) and cmHsp70.2 (aa 614-623) that are conserved among different species reside in the substrate-binding domain of Hsp70, with measured affinities of 0.42 nM and 0.44 nM, respectively. Validation of the compHsp70 ELISA revealed a high intra- and inter-assay precision, linearity in a concentration range of 1.56 to 25 ng/ml, high recovery rates of ‘spiked’ liposomal Hsp70 (>84%), comparable values between human serum and plasma samples, and no interference by food intake or age of the donors. Hsp70 concentrations in the circulation of patients with glioblastoma, squamous cell or adeno non-small cell lung carcinoma (NSCLC) at diagnosis were significantly higher than those of healthy volunteers. Hsp70 concentrations dropped concomitantly with the decrease in viable tumor mass on irradiation of patients with approximately 20 Gy (range 18 – 22.5 Gy) or after completion of radiotherapy (60 - 70 Gy). In summary, the compHsp70 ELISA presented herein provides a highly sensitive and reliable tool for measuring free and exosomal Hsp70 in liquid biopsies of tumor patients, levels of which can be used as a predictive tumor-specific biomarker, risk assessment and for monitoring therapeutic outcome.

Objective: The goal of this study was to analyse the attitudes and perceptions of emergency and mental health nurses through the validation of the SM-GIBED scale in specialised care in Spain on alcoholics and other drug-dependent patients. Design and Setting: This cross-sectional study was developed using the Spanish hospital version of the Seaman-Mannello scale to denominate the SM-GIBED scale. Participants: 170 Emergency and Mental Health Nursing from five Spanish Hospitals. Intervention: Self-administered questionnaire to analiyse the perceptions and attitudes about the drug addict and the alcoholic. Primary and Secondary Outcome Measures: A descriptive and inferential analysis of the study variables was carried out. A psychometric analysis was performed to validate the scale. Results: A total of 170 questionnaires were collected from 257 healthcare workers. Overall, 99.1% of the participants had contact with drug-dependent patients during their professional experience. Nearly 75% had difficulties in treating them. The psychometric analysis of the SM-GIBED scale in the Spanish context obtained values of KMO = 0.655 and Bartlett's test p < 0.000. Cronbach's alpha of 0.738 was obtained from the reliability analysis. A reliability analysis of each of the SM-GIBED questions found no case with an alpha lower than 0.71. In conclusion, positive aspects include an ingratiating attitude and subject-to-subject communication when nurses self-define as empathic and non-paternalistic. Among the negative aspects, there is a lack of communication skills and assertiveness with these patients. This highlights a certain degree of resignation and dissatisfaction when working with drug addicts.

Shrinking farm size and fragile farm resources pose a significant challenge to the sustainability of small-scale farms. Efficient resource utilization in small-scale farms is crucial to achieving farm sustainability through endogenous mechanisms. However, the precise mechanisms to integrate physical resources to achieve farm sustainability are not very clear yet. By capturing the interaction among farm resources as a network phenomenon, we identify the discrete resource interactions (RIs) in different types of small-scale farms of Indian Sundarbans, which are associated with higher farm sustainability. Thirty-two linkages, 11 reciprocal linkages, 22 triads, and three ‘core elements’ that occurred and cooccurred on highly sustainable farms are found to be critical in achieving farm sustainability. Using the properties of resource interaction networks as explanators of farm sustainability, we anticipate that sustainability in small-scale farms can be achieved by strategically creating new RIs on the farm. However, there may be limitations to such achievement depending on the nature of RI and type of farm. The analytical approach helps to understand the structural basis of sustainability in small-scale farms, and this approach can be used to achieve farm sustainability through the strategic integration of existing farm resources in the smallholder systems.

Constraint-based metabolic modeling approaches have enhanced our knowledge and understanding of the metabolism of prokaryotes and eukaryotes. This approach highly depends on the reconstruction process of genome-scale metabolic models (Mmodels). M-models can guide effective experimental design and yield new insights into the function and control of biological systems. Despite the recent advances in the automated generation of draft metabolic network reconstructions, the manual curation of these networks remains a labor-intensive and challenging task. Thus, these ten quick tips for the manual curation process are essential for optimizing high-quality metabolic model generation in less time. This collection of tips describes in great detail the resources and methods to ensure successful reconstruction. Furthermore, it increases the scope of other protocols of metabolic modeling by including resources to reconstruct eukaryotic organisms. Thus, all tips are applicable to a wide range of eukaryotic organisms. We believe this manuscript will interest a broad audience and researchers from different disciplines, spanning from microbiology and systems biology to biotechnology.

Although researchers have investigated widely the impact of IOD phases on human lives, only a few have examined such impacts on fisheries. In this study, we analyzed the influence of negative (positive) of IOD on a chlorophyll a (Chl-a) concentration as an indicator of phytoplankton biomass and small pelagic fish production in the eastern Indian Ocean (EIO) off Java. We also conducted field surveys in the EIO off Palabuhanratu Bay at the peak (October) and the end (December) of the 2019 positive IOD phase. Our findings show that the Chl-a concentration had a strong and robust association with the 2016 (2019) negative (positive) IOD phases. The negative (positive) anomalous Chl-a concentration in the EIO off Java associated with the negative (positive) IOD phase induced strong downwelling (upwelling), leading to the preponderant decrease (increasing) of small pelagic fish production in the EIO off Java.

This case study assessed marketing arrangements used by small scale farmers in the Lake Basin and Lower Eastern bean corridors of Kenya to determine which markets work for rural producers and what changes are needed to produce and supply sufficient quantities for trade. Using exploratory research, data was collected through focus group discussions with six farmer groups representing a total of 1255 bean farmers and key informant interviews with extension staff. The results indicated that 94% of the farmers produced beans before identifying buyers with only 6% participating in group marketing. Though spot-market transactions with brokers and traders provided ready cash for the farmers, formal buyers were perceived to be more reliable but difficult to find and, operated stringent requirements which were a barrier to entry. A theory of change to integrate smallholders into formal markets to sustainably produce and supply sufficient volumes for trade should entail a transformation agenda at four levels of the value chain: intensification of production through pure stand models with greater use of certified high yielding varieties; stable price guarantees; a market-driven research and extension service and; an enabling political, policy and business environment in the bean value chain. Further research is needed to pilot these changes in a case control study.

Digital Elevation Models (DEMs) are widely used in geographic and environmental studies. In the current work, the fusion of multi-source DEMs is investigated to improve the overall accuracy of public domain DEMs. Multi-scale decomposition is an important analytical method in data fusion. Three multi-scale decomposition methods – the wavelet transform (WT), bidimensional empirical mode decomposition (BEMD) and nonlinear adaptive multi-scale decomposition (N-AMD) - are applied to the 1-arc-second Shuttle Radar Topography Mission Global digital elevation model (SRTM-1 DEM) and the Advanced Land Observing Satellite World 3D – 30 m digital surface model (AW3D30 DSM) in China. Of these, the WT and BEMD are popular image fusion methods. A new approach for DEM fusion is developed using N-AMD (which is originally invented to remove the cycle from sunspots). Subsequently, a window-based rule is proposed for the fusion of corresponding frequency components obtained by these methods. Quantitative results show that N-AMD is more suitable for multi-scale fusion of multi-source DEMs, taking the ice cloud and land elevation satellite (ICESat) global land surface altimetry data as a reference. The vertical accuracy of the fused DEM shows significant improvements of 29.6% and 19.3% in a mountainous region and 27.4% and 15.5% in a low-relief region, compared to the SRTM-1 and AW3D30 respectively. Furthermore, a slope position-based linear regression method is developed to calibrate the fused DEM for different slope position classes, by investigating the distribution of the fused DEM error with topography. The results indicate that the accuracy of the DEM calibrated by this method is improved by 16% and 13.6%, compared to the fused DEM in the mountainous region and low-relief region respectively, proving that it is a practical and simple means of further increasing the accuracy of the fused DEM.

The mucopolysaccharidoses (MPS) are a group of 11 lysosomal storage diseases (LSDs) produced by mutations in the enzymes involved in the lysosomal catabolism of glycosaminoglycans. Most of the mutations affecting these enzymes may lead to changes in processing, folding, glycosylation, pH stability, protein aggregation, and defective transport to the lysosomes. The use of small molecules, called pharmacological chaperones (PCs), that can restore the folding, trafficking and biological activity of mutated enzymes has been extensively explored in LSDs as a therapeutic alternative. PCs have the advantage of wide tissue distribution, potential oral administration, lower production cost, and fewer issues of immunogenicity. In this paper, we will review the advances in the identification and characterization of PCs for the MPS. These molecules, mainly based in molecules mimicking the enzyme substrates, have been described for MPS II, IVA, and IVB, showing a mutation-dependent enhancement of the mutated enzymes. Although the results show the potential of this strategy, further studies should focus in the development of disease-specific cellular models that allow a proper screening and evaluation of the identified PCs. In addition, in vivo evaluation, both pre-clinical and clinical, should be performed, before they can become a real therapeutic strategy for the treatment of MPS patients.

Liquid biopsies are an integral part of the diagnosis of cancer. Here, we have extended previous validation studies of a new targeted NGS panel to include the detection of copy number amplifications (CNAs), fusions, and exon skipping variants. Detection of these gene classes included specimens from clinical and healthy donors and cell lines (fusions: ROS1, EML4-ALK, NTRK1), (exon skipping: MET exon 14), and (CNAs: HER2, CDK6, EGFR, MYC and MET). The limit of detection (LOD) for fusion/skipping was 42 copies (QC threshold = 3 copies) and was verified using 3 additional fusion/skipping variants. LOD for CNAs was 1.40-fold-change (QC threshold = 1.15-fold change) and was verified with 3 additional CNAs. In precision studies, all fusion/skipping variants were detected in all runs and all days of testing (n=18/18; 100%); average CV for repeatability was 20.5% (range 8.7% - 34.8%), and for reproducibility was 20.8% (range 15.7% - 30.5%). For CNAs, 28/29 (96.6%) copy gains were detected. For CNAs, average CV of 1.85% (range 0% to 5.49%) for repeatability and 6.59% (range 1.65% to 9.22%) for reproducibility. The test panel meets the criteria for being highly sensitive and specific and extends its utility for the detection of clinically relevant variants in cancer.

Earth's global surface temperature shows variability on an extended range of temporal scales and satisfies an emergent scaling symmetry. Recent studies indicate that scale invariance is not only a feature of the observed temperature fluctuations, but an inherent property of the temperature response to radiative forcing, and a principle that links the fast and slow climate responses. It provides a bridge between the decadal- and centennial-scale fluctuations in the instrumental temperature record, and the millennial-scale equilibration following perturbations in the radiative balance. In particular, the emergent scale invariance makes it possible to infer equilibrium climate sensitivity (ECS) from the observed relation between radiative forcing and global temperature in the instrumental era. This is verified in ensembles of Earth system models (ESMs), where the inferred values of ECS correlate strongly to estimates from idealized model runs. For the range of forcing data explored in this paper, the method gives best estimates of ECS between 2.3 and 3.4 K.

Postpartum depression (PPD) has serious effects on maternal and infant morbidity and mortality. This study aimed to determine the prevalence of postpartum depression in mothers of under-twos in military barracks in Lagos. The Edinburgh Postnatal Depression Scale (EPDS) and a modified version of the General Help-Seeking questionnaire (GHSQ) were administered to 316 mothers of under-twos in 3 of 12 military barracks in Lagos, Nigeria to determine PPD and major depressive events (MDE). Risk of PPD was established at EPDS scores of >12. Good help-seeking practices were ascribed to scores of 20 or more on the GHSQ. Risk of PPD was found in 15.5% of respondents, and good help-seeking in 3.8% and 11.4% for personal/emotional and harming self/baby respectively. Bivariate analysis using Chi square showed statistically significant positive associations between lower scores for EPDS and higher educational levels of respondents, perception of partner support and being in lower wealth quintiles (p<0.05). Use of the EPDS was accepted among mothers of children aged under two years. Opportunities to educate pregnant women and new mothers about PPD using existing social networks, perinatal and infant screening programmes in the barracks can be leveraged upon to improve mental health delivery as part of maternity care.

Discovery of inhibitors for endothelial-related transcription factors can contribute to the development of angiogenic therapies that treat diseases ranging from cardiovascular to cancer. The role of transcription factor Vezf1 in vascular development and regulation of angiogenesis has been defined by several earlier studies. Through construction of a computational model for Vezf1, work here has identified a novel small molecule drug capable of inhibiting Vezf1 from binding to its cognate DNA binding site. Using structure-based design and virtual screening of the NCI Diversity Compound Library, 12 shortlisted compounds were tested for their ability to interfere with the binding of Vezf1 to DNA using electrophoretic gel mobility shift assays. We identified one compound, T4, which has an IC50 of 20uM. Using murine endothelial cells, MSS31, we tested the effect of T4 on endothelial cell viability and angiogenesis by using tube formation assay. Our data show that addition of T4 in cell culture medium does not affect cell viability at concentrations lower or equal to its IC 50 but strongly inhibits the network formation by MSS31 in the tube formation assays. Given its potential efficacy, this inhibitor has significant therapeutic potential in several human diseases raging from wound healing to cancer.

The early detection of cutaneous melanoma, a potentially lethal cancer with rising incidence, is key to increase survival and therapeutic adjustment. Especially in stages II-IV biomarkers are urgently needed for adjuvant therapy purposes after resection and for treatment of metastatic patients. We here investigated if fatty acid (FA) and protein composition of small extracellular vesicles (sEV) deriving from plasma of 0-I, II, and III-IV stage melanoma patients (n=38) could reflect disease stage and thus function as biomarker. The subpopulation of sEV expressing CD81 (CD81sEV) was isolated by an ad hoc immune affinity technique from microvesicle-depleted plasma. Biological macromolecules were investigated by gas chromatography and mass spectrometry in CD81sEV. A higher content of FA and a decrease in Saturation Index (C18:0/C18:1), already detectable in early stages, distinguished patients’ from healthy donor CD81sEV. Proteomics (identifier PXD024434) detected an exclusive and significant increase of CD14, PON1, PON3 and APOA5 in stage II and a significant decrease of Rap1b in stage III-IV CD81sEV. The FA and proteomic stage dependent CD81sEV signature strengthens the potential of circulating sEV studies in providing discriminatory information for early diagnosis, prediction of metastatic behavior and follow up of melanoma patients.

In this work a modified version of the well-known Simple Water Balance (SWB) model, comprising here three parameters instead of one, was used. Although simple, the model was tested in large-scale river basins in east-central Greece, upstream two hydrometric stations. The available historic runoff records comprised 19 hydrologic years each, on a monthly basis. Thirteen among them were used for calibrating the model, whereas the six subsequent, for validating it. Two different efficiency criteria were used as a measure of performance of the modified model. Their values, calculated for both calibration and validation stages, were close and relatively high. Thus, keeping in mind both the size and complexity of the river basins studied, one can conclude that the modified model, despite its simplistic concept and lumped form, fits satisfactorily the historic runoff series.

Drug design is used for different applications of bioinformatics tools analyze DNA, genome, and sequence target region of a small organic molecule in order to understand the molecules of disease. Bioinformatics tools are identified a newly wide research field and minimize future risks through web servers and data mining. Clinical sample test performed with the bioinformatics tools as the biomedical detective. A particular structure and configuration of protein obliging in Drug design concluded Bioinformatics. This review bioinformatics tools and webserver will discuss functions of small organic molecules according to clinical pharmacology.

Lung cancer remains the leading cause of cancer-related death and it is usually diagnosed in advanced stages (stage III or IV). Recently, the availability of targeted strategies and of immunotherapy with checkpoint inhibitors (ICI) has favorably changed patient prognosis. Treatment outcome is closely related to tumor biology and interaction with the host immune microenvironment (TME). Whether for targeted therapies the response relies on the presence of specific genetic alterations in tumor cells, for ICI accurate biomarkers of response are lacking and clinical outcome likely depends on multiple factors, host and tumor-related. This paper is an overview of the ongoing research on predictive factors both from in-vitro/ex-vivo analysis (ranging from conventional pathology to molecular biology) and in-vivo analysis, where molecular imaging is showing an exponential growth and use due to the technological advancement and to the new bioinformatics approaches applied to image analyses that allow specific features recovery in specific tumor subclones.

Background: The phase III KEYNOTE-604 study confirmed the benefit of pembrolizumab combined with chemotherapy in the first-line treatment of extensive-stage small-cell lung cancer(ES-SCLC). Intergrated the clinical benefits of pembrolizumab and its high cost into account, this study aim to assess the cost-effectiveness of adding pembrolizumab to standard first-line etoposide-platinum (EP) for patients with ES-SCLC from the the US payer perspective. Methods: A Markov model was developed to compared the costs and quality-adjusted life-years (QALYs) of pembrolizumab plus EP and placebo plus EP over a 10-year time horizon. Clinical efficacy, treatment utilization and safety data were pooled from the KEYNOTE-604 trial. Utilities were obtained from published resources. Costs were mainly collected from Medicare in 2020. Sensitivity analyses were performed to examined the robustness of our model. Results: Adding pembrolizumab to standard first-line EP, resulted in better effectiveness than the use of EP alone for ES-SCLC by 0.22 QALYs. Pembrolizumab plus EP was dominated economically by placebo plus EP, leading to an incremental cost-effectiveness ratio(ICER) of $334,373/ QALY. Deterministic sensitivity analyses indicated that the uncertainty in model parameters exerts no substantial effect on our results. Probability sensitivity analysis indicated that probabilities for pembrolizumab plus EP being cost-effective within a wide rang of willingness to pay were modest. Conclusion: From the US payer perspective, the first-line treatment for ES-SCLC with pembrolizumab plus EP was not cost-effective compare with placebo plus EP. Although pembrolizumab combination chemotherapy was beneficial to the survival of ES-SCLC, price reduction may be the necessary measure to improve its cost-effectiveness.

Recently, there has been renewed interest in the performance, functionality, and sustainability of traditional small-scale storage interventions (check dams, farm bunds and tanks) used across India for the improvement of local water security. The Central Groundwater Board of India is en-couraging the construction of such interventions for the alleviation of water scarcity. It is of critical importance to understand the hydrological effect of these interventions at basin scales to maximise their effectiveness. The quantification of small-scale interventions in hydrological modelling is often neglected, especially in large-scale modelling exercises. A bespoke version of the GWAVA model was developed to assess the impact of interventions on the water balance of the Cauvery Basin and two smaller sub-catchments. Model results demonstrate that farm bunds appear to have a negligible effect on the estimated average annual simulated streamflow at the outlets of the two sub-catchments and the basin whereas tanks and check dams have a more significant effect. In-terventions generally were found to increase evaporation losses across the catchment. The model adaption used in this study provides a step-change in the conceptualisation and quantification of the consequences of small-scale storage interventions in large- or basin-scale hydrological models.

Size-based fungal growth studies have limitations. For example, the growth in size stops in closed systems once it reaches the borders and poorly describes the metabolic status, especially in the stationary phase. This might lead mycotoxin studies to unrealistic results. Color change could be a viable alternative as pigments are results of the mold’s metabolic activity. This study aimed to verify the possibility of using gray values and the RGB system to analyze the growth of Fusarium graminearum. It consisted color and area measurement using the ImageJ software for specimens grown in yeast extract agar (YEA). The results suggest the usability of color and gray values as reliable tools to analyze the growth of F. graminearum.

With reference to Planck scale, increasing support for large scale cosmic anisotropy and preferred directions and by considering an increasing ratio of Hubble parameter to angular velocity, right from the beginning of Planck scale, we make an attempt to estimate ordinary matter density ratio, dark matter density ratio, mass, radius, temperature, age and expansion velocity (from and about the baby universe in all directions). We would like suggest that, from the beginning of Planck scale, 1) Dark matter can be considered as a kind of cosmic foam responsible for formation of galaxies. 2) Cosmic angular velocity decreases with square of the decreasing cosmic temperature. 3) Increasing ratio of Hubble parameter to angular velocity plays a crucial role in estimating increasing cosmic expansion velocity and decreasing density ratios of dark matter and ordinary matter. 4) There is no need to consider dark energy for understanding cosmic acceleration.

In the last years, more and more studies highlight the advantages of complementing traditional master classes with additional activities that improve students´ learning experience. This combination of teaching techniques is specially advised in the field of structural engineering, where intuition of the structural response it is of vital importance to understand the studied concepts. This paper deals with the introduction of a new (and more encouraging) educational tool to introduce intuitively students in the dynamic response of structures excited with an educational shaking table. Most of the educational structural health monitoring systems use sensors to determine the dynamic response of the structure. The proposed tool is based on a radically different approach, as it is based on low-cost image-recognition techniques. In fact, it only requires the use an amateur camera, a black background and a computer. In this study, the effects of both the camera location and the image quality are also evaluated. Finally, to validate the applicability of the proposed methodology, the dynamic response of small-scale buildings with different typologies is analyzed. In addition, a series of surveys were conducted in order to evaluate the activity based on student´s satisfaction and the actual acquisition and strengthening of knowledge.

This study provides designs for a low-cost, easily replicable open source lab-grade digital scale that can be used as a precision balance. The design is such that it can be manufactured for use in most labs throughout the world with open source RepRap-class material extrusion-based 3-D printers for the mechanical components and readily available open source electronics including the Arduino Nano. Several versions of the design were fabricated and tested for precision and accuracy for a range of load cells. The results showed the open source scale was found to be repeatable within 0.1g with multiple load cells, with even better precision (0.01g) depending on load cell range and style. The scale tracks linearly with proprietary lab-grade scales, meeting the performance specified in the load cell data sheets, indicating that it is accurate across the range of the load cell installed. The smallest loadcell tested(100g) offers precision on the order of a commercial digital mass balance. The scale can be produced at significant cost savings compared to scales of comparable range and precision when serial capability is present. The cost savings increase significantly as the range of the scale increases and are particularly well-suited for resource-constrained medical and scientific facilities.

Quantitative trait loci (QTL) are genomic regions associated with phenotype variation of quantitative traits in a population. To date, a total of 267 QTL for 29 quantitative traits have been reported in 13 studies on flax. Of these, 200 QTL from 12 studies were identified based on genetic maps, scaffold sequences, or pre-released chromosome-scale pseudomolecules. Molecular markers for QTL identification differed across studies but were mainly based on simple sequence repeat (SSR) or single nucleotide polymorphism (SNP) markers. This article provides methods with software tools and database files to uniquely map SSR and SNP markers from different references onto the recently released chromosome-scale pseudomolecules. Using these methods, 195 QTL were successfully sorted onto the 15 flax chromosomes and grouped into 133 co-located QTL clusters. Mapping of QTL from different studies to the same reference enables comparisons and facilitates genome-wide QTL analysis, candidate gene scanning, and breeding applications.

Background: Real-world data on the molecular epidemiology of EGFR resistance mutations at or after progression with first- or second-generation EGFR-TKIs in patients with advanced NSCLC are lacking. Methods: This ongoing observational study was carried out by 23 hospital-based physicians in Greece. The decision to perform Cobas® EGFR Mutation Test v2 in tissue and/or plasma at disease progression was made before enrollment. For patients with negative/inconclusive T790M plasma-based results, tissue re-biopsy could be performed. Results: Ninety-six (96) eligible patients were consecutively enrolled (median age: 67.8 years) between July-2017 and September-2019. Of the patients, 98% were tested upon progression using plasma and 2% using tissue/cytology biopsy. The T790M mutation was detected in 16.0% of liquid biopsies. Tissue re-biopsy was performed in 22.8% of patients with a T790M-negative plasma result. In total, the T790M positivity rate was 21.9%, not differing between patients on first- or second-generation EGFR-TKI. Higher (≥2) ECOG performance status and longer (≥10 months) time to disease progression following EGFR-TKI treatment initiation were associated with T790M positivity. Conclusions: Results from plasma/tissue-cytology samples in a real-world setting, yielded a T790M positivity rate lower than previous reports. Fewer than one in four patients with negative plasma-based testing underwent tissue re-biopsy, indicating the challenges in routine care settings.

Insufficient mixing in large-scale bioreactors, provokes gradient zones of substrate, dissolved oxygen, pH and other parameters. E. coli responds to a high glucose, low oxygen feeding zone with the accumulation of mixed acid fermentation products, especially formate, but also with the synthesis of non-canonical amino acids, such as norvaline, norleucine and -methyl-norleucine. These amino acids can be mis-incorporated into recombinant products, which causes a problem for pharmaceutical production whose solution is not trivial. While these effects can also be observed in scale down bioreactor systems, these are challenging to operate. Especially the high-throughput screening of clone libraries is not easy, as fed-batch cultivations would need to be controlled via repeated glucose pulses with simultaneous oxygen limitation, as has been demonstrated in well controlled robotic systems. Here we show that not only glucose pulses in combination with oxygen limitation can provoke the synthesis of these non-canonical branched-chain amino acids, but also that pyruvate pulses produce the same effect. Therefore we combined the enzyme based glucose delivery method Enbase® in a PALL24 mini-bioreactor system and combined repeated pyruvate pulses with simultaneous reduction of the aeration rate. These cultivation conditions, produced an increase in the non-canonical branched chain amino acids norvaline and norleucine in both the intracellular soluble protein and inclusion body fractions with mini-proinsulin as an example product, and this effect was verified in a 15 L stirred tank bioreactor. To our opinion this cultivation strategy is easy to apply for the screening of strain libraries under standard laboratory conditions if no complex robotic and well controlled parallel cultivation devices are available.

Remote sensing technology provides a new way to explore the earth for geoscience applications. In the context of continuous deepening of geological research and the vigorous development of geospatial information science, 3D geological modeling technology has become a research hotspot in the intersection of earth science and information science. The traditional 3D geological modeling technology refers to underground 3D modeling using geological data. This modeling method can only display the underground scene in 3D visualization, but cannot display the surface in detail. In this study, remote sensing technology is adopted to improve the traditional 3D geological modeling method, so that geological modeling can be integrated with remote sensing image, and a new 3D geological modeling method based on remote sensing technology is developed. This method can perform integrated 3D visualization of underground and aboveground scenes, which provides a new way for disaster prevention and reduction, geological prospecting and tectonic interpretation. The new 3D geological modeling method is mainly applied in the geological field, and has made new progress in multi-source heterogeneous geological data fusion, large-scale high-precision modeling, geological grid subdivision, attribute modeling technology, remote sensing image fusion and other aspects. Taking the Ya'an area as an example, this paper makes use of the new generation of 3D geological modeling technology to carry out 3D geological modeling and visual display. The 3D visualization in Ya'an area verifies the feasibility and effectiveness of the new 3D geological modeling method based on remote sensing technology in the current data environment.

[NiFe]-hydrogenases are gas-processing metalloenzymes that catalyze the conversion of dihydrogen (H2) to protons and electrons in a broad range of microorganisms. Within the framework of green chemistry, the molecular proceedings of biological hydrogen turnover inspired the design of novel catalytic compounds for H2 generation. The bidirectional “O2-sensitive” [NiFe]-hydrogenase from Escherichia coli HYD-2 has recently been crystallized; however, a systematic infrared characterization in the presence of natural reactants is not available yet. In this study, we analyze HYD-2 from E. coli by in situ ATR FTIR spectroscopy under quantitative gas control. We provide an experimental assignment of all catalytically relevant redox intermediates alongside the O2- and CO-inhibited cofactor species. Furthermore, the reactivity and mutual competition between H2, O2, and CO was probed in real time, which lays the foundation for a comparison with other enzymes, e.g., “O2-tolerant” [NiFe]-hydrogenases. Surprisingly, only Ni-B was observed in the presence of O2 with no indications for the “unready” Ni-A state. The presented work proves the capabilities of in situ ATR FTIR spectroscopy as an efficient and powerful technique for the analysis of biological macromolecules and enzymatic small molecule catalysis.

The role played by non extensive thermodynamics in physical systems has been under intense debate for the last decades. With many applications in several areas, the Tsallis statistics has been discussed in details in many works and triggered an interesting discussion on the most deep meaning of entropy and its role in complex systems. Some possible mechanisms that could give rise to non extensive statistics have been formulated along the last several years, in particular a fractal structure in thermodynamics functions was recently proposed as a possible origin for non extensive statistics in physical systems. In the present work we investigate the properties of such fractal thermodynamical system and propose a diagrammatic method for calculations of relevant quantities related to such system. It is shown that a system with the fractal structure described here presents temperature fluctuation following an Euler Gamma Function, in accordance with previous works that evidenced the connections between those fluctuations and Tsallis statistics. Finally, the fractal scale invariance is discussed in terms of the Callan-Symanzik Equation.

Studying hydro-meteorological factors variations and its links to large-scale atmospheric circulation systems can facilitate the understanding of the hydrological processes and sustainable water resources management in the source region of the Yangtze River (SRYR). Currently, researches mostly focused on the temporal and spatial variation characteristics in hydro-meteorological factors; however, researches on the hydro-meteorological variations and its links to large-scale atmospheric circulation systems in the SRYR are scarce. Based on long-term hydro-meteorological and reanalysis data, this research investigated multiscale variations of hydro-meteorological factors and its links to large-scale atmospheric circulation characteristic indices during 1957~2012 in the SRYR. The results showed that the amounts of streamflows and precipitation in the SRYR declined during the 1990s. Since the 2000s, the amounts of streamflows and precipitation had increased significantly climate in the SRYR. The change trends of precipitation and streamflows in the SRYR are synergetic at annual and seasonal scales, and have three significant periods, namely 3~5 years, 15–20 years and 30–40 years. The South Asia monsoon (SAM) plays a relatively more important role in the hydro-meteorological factors changes in the SRYR. The relative contributions of SAM to streamflows and precipitation changes were 83.6% and 78%, respectively. During the driest (wettest) year, the SAM is relatively weak (strong), and brings less (more) southwest airflow into the SRYR, less (more) precipitation and streamflows will be generated in the SRYR.

Metabolites are at the end of the gene-transcript-protein-metabolism cascade. As such, metabo-lomics is the omic approach that offers the most direct correlation with phenotype. This allows that, where genomics, transcriptomics and proteomics fail to explain a trait, metabolomics might give an answer. Complex phenotypes, which are determined by the influence of multiple small effect alleles, are an example of these situations. Consequently, the interest in metabolomics has increased ex-ponentially in the last years. As a newer discipline, the metabolomics bioinformatics analysis pipe-lines are not as standardized as in the other omic approaches. In this review we synthesized the different steps that need to be carried out to obtain biological insight from the annotated metabolite abundance raw data. These steps were grouped in three different modules: preprocessing, statistical analyses and metabolic pathway enrichment. We included within each one of them the different state-of-the art procedures and tools that can be used depending on the characteristics of the study, providing details about the characteristics of each method has, as well as the issues the reader might encounter. Finally, we introduce genome scale metabolic modeling as a tool for obtaining pseu-do-metabolomic data in situations where its acquisition is difficult, being possible to analyze the resulting data with the modules of the described workflow.

Environmental conditions, such as temperature, carbon dioxide, and nutrient availability, are altered by urban conditions at regional scales with potential for impact on tree leaf structure. Our goal was to compare leaf morphological characteristics driven by physiological acclimation in red maple (Acer rubrum L.) trees in deciduous forests embedded in a small (Newark, DE) and a large (Philadelphia, PA) city. The study was conducted in six urban forests on eighteen mature red maple trees in a long-term urban forest network. We hypothesized that red maples in Philadelphia forests compared to Newark forests will have a thicker upper epidermal layer, spongy palisade and mesophyll layer, longer and wider stomates, and lower stomate density. Additionally, we hypothesized that red maples in Philadelphia forests compared to Newark forests will have lower leaf water content and specific leaf area, and greater leaf thickness, fresh leaf weight, dry leaf weight, and leaf dry matter content. Our results for stomate length and stomate width supported our predictions; red maple leaves had longer and wider stomates in Philadelphia forests than in Newark forests. The increased stomate size in red maple trees suggests potential altered gas exchange behavior and mutual abiotic stress mitigation responses in red maple to greater urbanization impacts in Philadelphia forests. This supports previous findings of possible physiological and biochemical acclimation of red maple trees to urban conditions. Furthermore, the findings from this study suggest red maple trees may be a good biomonitor of regional scale impacts in urban environments.

A naked human eye can perceive objects down to a millimeter length. While lenses and microscopes have overcome this limit, the human mind still lacks perspective when navigating conventional scales (1), especially in the range that are less palpable to naked human eye (2,3). This problem is particularly acute in the context of science communication, where the conventional scale bar units facilitate little comprehension regarding the perception for factorial size differences (3). Here we aim to bridge the gap of scale factors and perspectives using a universal toolkit of objects, which can help comprehend the relative change in length dimensions up to 13 orders of magnitude difference. We further have demonstrated the use of such a universal object toolkit as a length perceptive scale by illustrating and narrating biological phenomena. The meter to picometer ‘length perceptive scale’ proposed here has the potential to cover majority of length scales present in the biological realm, and is analogous to the time compression methods widely used in explaining cosmos timeline (4). Our toolkit can also be calibrated according to the users need in their scientific communication and illustrations, which will aid the readers’ benefit in understanding the length scale perception of illustrated phenomenon.

Light and heat resources are ample in Xinjiang plain oasis region. Planting structure is single in irrigation area, which leads to severe seasonal water shortages due to high concentration of water utilization. Therefore, how to make full use of light and heat resources to develop oasis agriculture without expanding planting scale has become the focus of research. The biannual cropping patterns are possible solutions to the problem. Manas River Irrigation area, which is located on the northern slope of Tianshan Mountain in Xinjiang in China is regarded as a typical case study to analyze the suitable planting structure and planting scale for biannual cropping pattern. The effects of optimizing planting patterns on alleviating the contradiction between water supply and water need，and the efficiency of water resources utilization was also studied. The results of the study show that：(1) the suitable planting scales of Manas River irrigation area in wet year (P = 25%), normal year (P = 50%), and low flow year (P = 75%) are about 72.66%, 78.73% and 83.91% of the current planting scale. (2) After the planting structure was optimized, the water use process in the irrigation area extends from May to August at present to April to November. The water use ratio at the peak period of water use decreased from 0.847 to 0.601, and the water use peak was significantly dispersed. (3) Economic benefits per cubic metre of water of the biannual cropping patterns increased from 8.65 yuan·m⁻³ at present to 9.45 yuan·m⁻³, 10.31 yuan·m⁻³ and 11.43 yuan·m⁻³ in wet year (P = 25%), in normal year (P = 50%) and low flow year (P = 75%) respectively, which proved that replanting crops could improve the efficiency of water resources utilization in irrigated areas. Therefore, the optimal planting pattern can be implemented to improve the utilization efficiency of soil and water resources in irrigation area in the arid oasis with single planting pattern with excessive concentration of water use peak and serious water shortage.

The paper briefly reviews the Clifford algebras of space Cl(3,0) and anti-space Cl(0,3) with a particular focus on the paravector representation, emphasizing the fact that both algebras have an isomorphic center represented just by two coordinates. Since the paravector representation allows assigning the scalar element of grade 0 to the time coordinate, we consider the relativity in such two-dimensional spacetime for a uniformly accelerated frame with the constant acceleration 3Hc. Using the Rindler coordinate transformations in two-dimensional spacetime and then applying it to Minkowski coordinates, we obtain the FLRW metric, which in the case of the Clifford algebra of space Cl(3,0) corresponds to the anti-de Sitter (AdS) flat (k=0) case, the negative cosmological term and an oscillating model of the universe. The approach with anti-Euclidean Clifford algebra Cl(0,3) leads to the de Sitter model with the positive cosmological term and the exact form of the scale factor used in modern cosmology.

An accurate understanding of jointed rock mass behavior is important in many applications ranging from deep geological disposal of nuclear waste to deep mining to urban geoengineering projects. The roughness of rock fractures and the matching of the fracture surfaces are the key contributors to the shear strength of rock fractures. In this research, push shear tests with three normal stress levels of 3.6, 6.0, and 8.5 kPa were conducted with two granite samples with artificially induced well-matching tensile fractures with sizes of 500 mm × 250 mm and 1000 mm × 500 mm. The large sample reached on average a -60 % weaker peak shear stress than the medium-sized sample, and a strong negative scale effect was observed in the peak shear strength. The roughness of the surfaces was measured using a profilometer and photogrammetry. The scale-corrected profilometer-based method (JRC) underestimates the peak friction angle for the medium-sized slabs by -27 % for the medium sample and -9 % for the large sample. The photogrammetry-based (Z’2) method produces an estimate with -7% (medium) and +12 % (large) errors. The photogrammetry-based Z’2 is an objective method that consistently produces usable estimates for the JRC and peak friction angle.

MicroRNAs (miRNAs) are a class of small non-coding RNAs, which function as regulators of gene expression and contribute in numerous physiological processes. However, little is known referring to miRNAs function in insect chemosensation. In the current study, nine small RNA libraries were constructed and sequenced from the antennae of nymphs, adult males and females of Apolygus lucorum. In total, 399 miRNAs were identified including 275 known and 124 novel miRNAs. Known miRNAs were classified into 71 families, amongst which, 23 families were insect-specific. Expression profile analysis showed that miR-7-5p_1 was the most abundant miRNAs in the antennae of A. lucorum. Altogether, 69708 target genes related to biogenesis, membrane and binding activities were predicted for 399 miRNAs. Particularly, 15 miRNAs were found to target 16 olfactory genes. These miRNAs could be involved in regulation of olfactory-associated genes ex-pression. Comparing the antennae of nymphs, adult males and females, 94 miRNAs were found to be differentially expressed. The expression levels of some differentially expressed miRNAs measured by qPCR were consistent with sequencing results. This study provides a global miRNAs transcriptome in the antennae of A. lucorum and valuable information for further investigation on miRNA-mRNA interactions, especially the functions of miRNAs in regulating chemosensation.

Activating mutations in the Epidermal Growth Factor Receptor gene occur as early cancer-driving clonal events in a subset of patients with non-small cell lung cancer (NSCLC) and result in increased sensitivity to EGFR-tyrosine-kinase-inhibitors (EGFR-TKIs). Despite very frequent and often prolonged clinical response to EGFR-TKIs, virtually all advanced EGFR-mutated (EGFRM+) NSCLCs inevitably acquire resistance mechanisms and progress at some point during treatment. Additionally, 20-30% of patients do not respond or respond for a very short time (< 3 months) because of intrinsic resistance. While several mechanisms of acquired EGFR-TKI-resistance have been determined analyzing tumor specimens obtained at disease progression, the factors causing intrinsic TKI-resistance are less understood. However, recent comprehensive molecular-pathological profiling of advanced EGFRM+ NSCLC at baseline has illustrated the co-existence of multiple genetic, phenotypic, and functional mechanisms that may contribute to tumor progression and cause intrinsic TKI-resistance. Several of these mechanisms have been further corroborated by preclinical experiments. Intrinsic resistance can be caused by mechanisms inherent EGFR or by EGFR-independent processes, including genetic, phenotypic or functional tumor changes. This comprehensive review describes the identified mechanisms connected with intrinsic EGFR-TKI-resistance and differences and similarities with acquired resistance and among clinically implemented EGFR-TKIs of different generations. Additionally, the review highlights the need for extensive pre-treatment molecular profiling of advanced NSCLC for identifying inherently TKI-resistant cases and designing potential combinatorial targeted strategies to treat them.

Background: Plasma metabolites are associated with cognitive and physical function in the elderly. Because cerebral small vessel disease (SVD) and neurodegeneration are common causes of cognitive and physical function decline, the primary objective of this study was to investigate the associations of six plasma metabolites (two plasma phosphatidylcholines [PCs]: PC aa C36:5 and PC aa 36:6 and four sphingomyelins [SMs]: SM C26:0, SM [OH] C22:1, SM [OH] C22:2, SM [OH] C24:1) with magnetic resonance imaging (MRI) features of cerebral SVD and neurodegeneration in older adults. Methods: This study included 238 older adults in the Atherosclerosis Risk in Communities study at the fifth exam. Multiple linear regression was used to assess the association of each metabolite (log-transformed) in separate models with MRI measures except lacunar infarcts, for which binary logistic regression was used. Results: Higher concentrations of plasma PC aa C36:5 had adverse associations with MRI features of cerebral SVD (odds ratio of 1.69 [95% confidence interval: 1.01, 2.83] with lacunar infarct, and beta of 0.16 log [cm³] [0.02, 0.30] with log [White Matter Hyperintensities (WMH) volume]) while higher concentrations of 3 plasma SM (OH)s were associated with higher total brain volume (beta of 12.0 cm³ [5.5, 18.6], 11.8 cm³ [5.0, 18.6], and 7.3 cm³ [1.2, 13.5] for SM [OH] C22:1, SM [OH] C22:2, and SM [OH] C24:1, respectively). Conclusions: This study identified associations between certain plasma metabolites and brain MRI measures of SVD and neurodegeneration in older adults, particularly higher SM (OH) concentrations with higher total brain volume.

Recent studies on seafloor mapping have presented different modelling methods for the automatic classification of seafloor sediments. However, most of these studies have applied these models to seafloor data with appropriate number of ground-truth samples, which raises the question whether these methods are applicable to studies with smaller numbers of ground-truth data. In this study, we aim to address this issue by conducting sediment class-specific predictions using ensemble modelling to map areas with limited or without ground-truth data and combined with hydro-acoustic datasets. The resulting class-specific maps were then assembled into one map, where the most probable class was assigned to the appropriate location. Our approach was able to predict sediment classes without bias to the class with more ground-truth data and produced reliable seafloor sediment distributions maps that can be used for seafloor monitoring. Sediment shifts of a heterogenous seafloor in the Sylt Outer Reef, German North Sea were also assessed to understand the sediment dynamics in the area. The analyses of sediment shifts showed that the western area of the Sylt Outer Reef is highly active, and the results of the analyses assisted in providing recommendations on future seafloor monitoring activities.

Photoelectrochemical systems have the potential to contribute to de-carbonation of the energy system because solar energy can be directly converted to hydrogen which can be burnt without the release of greenhouse gases. However, meaningful deployment of photoelectrochemical (PEC) technology in the global energy system, even when highly efficient scaled up devices become available, shall only be a reality when their safe and reliable operation can be guaranteed over serveral years of service life. The first part of the review discusses the importance of hermetic sealing of up scaled PEC device provided by the casing and sealing joints from a reliability and risk perspective. The second part of the review presents a survey of fully functional devices and early demonstrators and uses this to establish the extent to which the state of the art in PEC device design address the issue of hermetic sealing. The survey revealed that current material choices and sealing techniques are still unsuitable for scale –up and commercialization. Accordingly, we examined possible synergies with related photovoltaic and electrochemical devices that have been commericalised and derived therefrom, recommendations for future research routes that could accelerate the development of hermetic sealings of PEC devices.

Many models have been proposed to explain the intergalactic redshift using different observational data and different criteria for the goodness-of-fit of a model to the data. The purpose of this paper is to examine several suggested models using the same supernovae Ia data and gamma-ray burst (GRB) data with the same goodness-of-fit criterion and weigh them against the standard $\text{Λ}$ CDM model. We have used the redshift – distance modulus ( $z-\mu$ ) data for 580 supernovae Ia with $0.015\le z\le 1.414$ to determine the parameters for each model, and then use these model parameter to see how each model fits the sole SNe Ia data at $z=1.914$ and the GRB data up to $z=8.1$ . For the goodness-of-fit criterion, we have used the chi-square probability determined from the weighted least square sum through non-linear regression fit to the data relative to the values predicted by each model. We find that the standard ΛCDM model gives the highest chi-square probability in all cases albeit with a rather small margin over the next best model - the recently introduced nonadiabatic Einstein de Sitter model. We have made ( $z-\mu$ ) projections up to $z=1096$ for the best four models. The best two models differ in $\mu$ only by 0.328 at $z=1096$ , a tiny fraction of the measurement errors that are in the high redshift datasets.

Cancer cells are adept at reprogramming energy metabolism and the precise manifestation of this metabolic reprogramming exhibits heterogeneity across individuals (and from cell to cell). In this study, we analyzed the metabolic differences between interpersonal heterogeneous cancer phenotypes. We used divergence analysis on gene expression data of 1156 breast normal and tumor samples from The Cancer Genome Atlas (TCGA) and integrated this information with a genome-scale reconstruction of human metabolism to generate personalized, context-specific metabolic networks. Using this approach, we classified the samples into four distinct groups based on their metabolic profiles. Enrichment analysis of the subsystems indicated that amino acid metabolism, fatty acid oxidation, citric acid cycle, androgen and estrogen metabolism and ROS detoxification distinguished these four groups. Additionally, we developed a workflow to identify potential drugs that can selectively target genes associated with the reactions of interest. MG-132 (a proteasome inhibitor) and OSU-03012 (a celecoxib derivative) were the top-ranking drugs identified from our analysis and known to have anti-tumor activity. Our approach has the potential to provide mechanistic insights into cancer-specific metabolic dependencies, ultimately enabling the identification of potential drug targets for each patient independently, contributing to a rational personalized medicine approach.

There have been several cases of large-scale wind generators (WGs) tripping off caused by untimely fault removing in recent years. Currently, the discoordination between the box-type transformer fuse protection (BTFP) and two-section collecting line current protection (CLCP) brings a security risk to wind farm. In order to ensure the selectivity, the first section (Sec-I) CLCP should be set a enough interval that is longer than the fuse melting time, and another interval is set for the Sec-II CLCP, which weakens the speed of the CLCP. When a fault occurs on the collecting line, there is no doubt that WGs cannot work too long in abnormal operation, which may cause WGs to be placed off the grid. For a power system with high penetration of wind power, large-scale WGs tripping off will cause a great power shortage, and affect the stability of the power system. The selectivity and sensitivity of the CLCP is analyzed in detail to make the CLCP speed better. Considering the fault ride-through ability of WGs, the fault clear time is an important factor to lead to large-scale WGs tripping off. Two main works are done in this paper. The first is to accelerate the speed of the Sec-I CLCP though reducing the protection zone. Another one is introduce the risk assessment module into the CLCP, which not only improve the speed of the CLCP but also ensure the safety of the wind farm during faults. According to the deference in trip-off causes of WGs, the matching functions are created to assess the trip-off risk of WGs on the spot. In the case of fault, the trip-off risk indicators of WGs are timely updated to data sharing center and open to the CLCPs. The set of risk indicators is divided into several subsets according to the risk range. The dynamic changes of the subsets during fault help to improved CLCP scheme. This scheme can accelerate protection speed based on the increasing risk of large-scale WGs tripping off in wind farms. Compared with traditional CLCP, this approach can make the CLCP combines selectivity and speed better based on the analysis of the ride- through ability of WGs.

A robust hydrological assessment is challenging in regions where human interference, within all aspects of the hydrological system, significantly alters the flow regime of rivers. The challenge was to extend a large-scale water resources model, GWAVA, to better represent water resources without increasing the model complexity. A groundwater and a regulated reservoir routine were incorporated into GWAVA using modifications of the existing AMBHAS-1D and Hanasaki methodologies, respectively. The groundwater routine can be varied in complexity when sufficient input data is available but fundamentally is driven by three input parameters. The reservoir routine was extended to account for the presence of large, regulated reservoirs using two calibratable parameters. The additional groundwater processes and reservoir regulation was tested in two highly anthropogenically influenced basins in India: the Cauvery and Narmada. The inclusion of the revised groundwater routine improved the simulation of streamflow in the headwater catchments and was successful in improving the representation of the baseflow component. In addition, the model was able to produce a time series of daily groundwater levels, recharge to groundwater and groundwater abstraction. The regulated reservoir routine improved the simulation of streamflow in catchments downstream of major reservoirs, where the streamflow was largely reflective of reservoir releases, when calibrated using downstream observed streamflow records. The model was able to provide a more robust representation of the annual volume and daily outflow released from the major reservoirs and simulate the major reservoir storages adequately. The addition of one-dimensional groundwater processes and a regulated reservoir routine proved successful in improving the model performance and traceability of water balance components, without excessively increasing the model complexity and input data requirements.

This study investigated the removal characteristics of N-nitrosamines and their precursors at three pilot-scale water reclamation plants. These plants applies different integrated membrane systems: (1) microfiltration (MF) / nanofiltration (NF) / RO; (2) sand filtration/three-step RO; and (3) ultrafiltration (UF) / NF and UF / RO. Variable removal of N-nitrosodimethylamine (NDMA) by the RO membrane processes could be attributable to membrane fouling and feed water temperature. The effect of membrane fouling on N-nitrosamines removal was extensively evaluated at one of the plants by conducting one month of operation and chemical cleaning of the RO membrane element. Membrane fouling enhanced N-nitrosamines removal by the pilot-scale RO membrane process. This finding contributes to better understanding of variable removal of NDMA by RO membrane processes. This study also investigated the removal characteristics of N-nitrosamines precursors. The NF and RO membrane processes greatly reduced NDMA formation potential (FP), but the UF process had little effect. The contributions of MF, NF, and RO membrane processes for reducing FPs of NDMA, N-nitrosopyrrolidine (NPYR) and N-nitrosodiethylamine (NDEA) were different, suggesting different size distributions of their precursors.

Following the coronavirus disease 2019 (COVID-19) pandemic, several studies have examined the possibility of correlating the virulence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, to the climatic conditions of the involved sites; however, inconclusive results have been generally obtained. Although either air temperature or humidity cannot be independently correlated with virus viability, a strong relationship between SARS-CoV-2 virulence and the specific enthalpy of moist air appears to exist, as confirmed by extensive data analysis. Given this framework, the present study involves a detailed investigation based on the first 20–30 days of the epidemic before public health interventions in 30 selected Italian provinces with rather different climates, here assumed as being representative of what happened in the country from North to South, of the relationship between COVID-19 distributions and the climatic conditions recorded at each site before the pandemic outbreak. Accordingly, a correlating equation between the incidence rate of the pandemic and the average specific enthalpy of atmospheric air was developed, and an enthalpy-based seasonal virulence risk scale was proposed as a tool to predict the potential danger of COVID-19 spread due to the persistence of weather conditions favorable to SARS-CoV-2 viability. For practical applications, a conclusive risk chart expressed in terms of coupled temperatures and relative humidity (RH) values was provided, showing that safer conditions occur in case of higher RH at the highest temperatures, and of lower RH at the lowest temperatures. The proposed risk scale was in agreement with the available infectivity data in the literature for a number of cities around the world.

The vulnerability of alpine environments to climate change presses an urgent need to accurately model and understand these ecosystems. Popularity in use of digital elevation models (DEMs) to derive proxy environmental variables has increased over the past decade, particularly as DEMs are relatively cheaply acquired at very high resolutions (VHR; <1m spatial resolution). Here, we implement a multiscale framework and compare DEM-derived variables produced by Light Detection and Ranging (LiDAR) and stereo-photogrammetry (PHOTO) methods, with the aims of assessing their relevance and utility in species distribution modelling (SDM). Using a case study on the arctic-alpine plant Arabis alpina in two valleys in the western Swiss Alps, we show that both LiDAR and PHOTO technologies can be relevant for producing DEM-derived variables for use in SDMs. We demonstrate that PHOTO DEMs rivalled the accuracy of LiDAR, putting the current paradigm of LiDAR being the more accurate of the two methods into question. We obtained DEMs at spatial resolutions of 6.25cm-8m for PHOTO and 50cm-32m for LiDAR, where we determined that the optimal spatial resolutions of DEM-derived variables in SDM were between 1 and 32m, depending on the variable and site characteristics. We found that the reduced extent of PHOTO DEMs altered the calculations of all derived variables, which had particular consequences on their relevance at the site with heterogenous terrain. However, for the homogenous site, we found that SDMs based on PHOTO-derived variables generally had higher predictive powers than those derived from LiDAR at matching resolutions. From our results, we recommend carefully considering the required DEM extent to produce relevant derived variables. We also advocate implementing a multiscale framework to appropriately assess the ecological relevance of derived variables, where we caution against the use of VHR-DEMs finer than 50cm in such studies.

Recently, the relationship between emotional arousal and depression has been studied. Focusing on this relationship, we first developed an arousal level voice index (ALVI) to measure arousal levels using the Interactive Emotional Dyadic Motion Capture database. Then, we calculated ALVI from the voices of depressed patients from two hospitals (Ginza Taimei Clinic [GTC] and National Defense Medical College hospital [NDMC]) and compared them with the severity of depression as measured by the Hamilton Rating Scale for Depression (HAM-D). Depending on the HAM-D score, the datasets were classified into a no depression (HAM-D&lt;8) and a depression group (HAM-D≥8) for each hospital. A comparison of the mean ALVI between the groups was performed using the Wilcoxon rank-sum test and a significant difference at the level of 10% (p = 0.094) at GTC and 1% (p = 0.0038) at NDMC was determined. The area under the curve (AUC) of the receiver operating characteristic was 0.66 when categorizing between the two groups for GTC, and the AUC for NDMC was 0.70. The relationship between arousal level and depression severity was indirectly suggested via ALVI.

Management of multiple primary cancers, a not so infrequent event in oncology practice, is a critical issue due to the lack of literature . In this study, we reported the case of a patient with metachronous double metastatic non small cell lung cancer (NSCLC) and pancreatic ductal adenocarcinoma (PDAC) who received gefitinib in combination with gemcitabine plus nab-paclitaxel and with mFOLFOX6 in first and second line, respectively. She achieved a progression free survival and an overall survival (OS) of 28 months for NSCLC and PFS-1 and OS of 20 and 13 months, respectively for PDAC. Moreover, the combination of gefitinib and chemotherapies treatments displayed a good safety profile. Given the insignificant frequency of this case, we performed a molecular characterization of both neoplasms with the aim to investigate the existence of particular activated pathways and/or similar immunological mutations. it is interesting to note that two neoplasms shared a commune mutation of B7-H3 gene, with the consecutive impairment of its expressed protein. In both PDAC and NSCLC, the expression of this protein was associated with a worse survival. Since B7-H3 is an anti-apoptotic protein, the reduction of its expression or function should justify a pro-apoptotic activity with a putative justification of the long survival of the patient considered in this report.

Biological gels (bio-gels) are hydrated polymer networks that serve diverse biological functions, which often lead to intentional or unintentional exposure to particulate matter. In this work, we derive a microscopically motivated framework that enables the investigation of penetration mechanisms into bio-gels. We distinguish between two types of mechanisms: spontaneous (unforced) penetration and forced penetration. Using experimental data available in literature, we exploit the proposed model to characterize and compare between the micro-structures of respiratory, intestinal, and cervicovaginal mucus and two types of biofilms. Next, we investigate the forced penetration process of spherical and ellipsoidal particles into a locally quadrilateral network. The proposed framework can be used to improve and complement the analysis of experimental findings in vitro, ex vivo, and in vivo. Additionally, the insights from this work pave the way towards enhanced designs of nano-medicines and allow to assess risk factors related to the nano-pollutants exposure.

The selenoprotein glutathione peroxidase 4 (GPX4) is one of the main antioxidant mediators in the human body. Its central function involves the reduction of complex hydroperoxides into their respective alcohols often using reduced Glutathione (GSH) as a reducing agent. GPX4 has become a hotspot therapeutic target in biomedical research following its characterization as a chief regulator of ferroptosis, and its subsequent recognition as a specific pharmacological target for the treatment of an extensive variety of human diseases including cancers and neurodegenerative disorders. Several recent studies have provided insights into how GPX4 is distinguished from the rest of the glutathione peroxidase family, the unique biochemical properties of GPX4, how GPX4 is related to lipid peroxidation and ferroptosis, and how the enzyme may be modulated as a potential therapeutic target. This current report aims to review the literature underlying all these insights and present an up-to-date perspective on the current understanding of GPX4 as a potential therapeutic target.

The aim of this study is to provide the scientists with a straightforward correlation that can be applied for predicting the Fanning friction factor and consequently the pressure drop during blood flow in small caliber vessels. Due to the small diameter of the conduit, the Reynolds numbers are low and thus the flow is laminar. The study has been conducted using CFD simulations validated with relevant experimental data acquired using an appropriate experimental set-up. The experiments concern pressure drop measurement during the flow of a blood analogue that follows the Casson model, i.e. an aqueous glycerol solution that contains a small amount of xanthan gum and exhibits similar behavior to blood, in a smooth, stainless steel microtube (L=5.6cm and D=400 μm). The interpretation of the resulting numerical data led to the proposal of a simplified model that incorporates the effect of the flow rate, the hematocrit value (35-55%) and the vessel diameter (300-1800 μm) and predicts with better than ±10% the Fanning friction factor and consequently the pressure drop during laminar blood flow in small caliber vessels.

Low charge density nanometric ions were recently shown to bind strongly to neutral hydrated matter in aqueous solution. This phenomenon, called (super-)chaotropic effect, arises from the partial dehydration of both, the nano-ion and the solute, leading to a high gain in enthalpy. Here, we investigate the chaotropic effect of the polyoxometalate α-PW12O403- on the triblock copolymer P84: (EO)19(PO)43(EO)19 with (EO)19 the polyethoxylated and (PO)43 the polypropoxylated chains. The combination of phase diagrams, spectroscopic (nuclear magnetic resonance) and scattering (small angle neutron/X-ray scattering) techniques reveals that (i) below the micellization temperature of P84, PW12O403- exclusively binds to the propylene oxide moiety of P84 unimers and (ii) above the micellization temperature, PW12O403- mostly adsorbs on the ethylene oxide micellar corona. The preferential binding of the PW12O403- to the PPO chain over the PEO chains suggests that the binding is driven by the chaotropic effect and reinforced by the hydrophobic effect. At higher temperatures, the copolymer micellization leads to the displacement of PW12O403- from the PPO chain to the PEO chains. This study deepens the understanding of the subtle interplay between the chaotropic and hydrophobic effects in complex salt-organic matter solutions.

The signal transduction pathways of estrogen receptors (ER) mainly includes gene pathway and non-gene pathway. Studies have shown that the gene pathway of ER is related with the expression of nuclear proteins, and this is the key issue for our current research. With the GEO database analysis, Human centromere protein F (CENPF) is highly expressed in adenocarcinoma of lung (LUAD), and the co-expression of CENPF and ERβ was found in the nucleus of LUAD cells. Meanwhile, CENPF and ERβ2/5 were related with T stage and poor prognosis (P<0.05). Knockdown of CENPF gene significantly inhibited the biological effects of LUAD cells, the tumor growth of mice and the expression of ERβ2/5 (P<0.05). Further, group experiments showed that knockdown CENPF inhibits biological effects of LUAD cells mediated by ERβ pathway. All the results indicated that both CENPF and ERβ2/5 play important roles in the progression of LUAD, and knockdown of CENPF can inhibit the progression of LUAD by inhibiting the expression of ER2/5. Thus, the development of inhibitors against ERβ2/5 subtype and CENPF remained more effective in improving the therapeutic effect of LUAD.

HIV-1 Tat protein interacts with TAR RNA and recruits CDK9/cyclin T1 and other host factors to induce HIV-1 transcription. Thus Tat-TAR RNA interaction, which is unique for HIV-1, represents an attractive target for anti-HIV-1 therapeutics. To target Tat-TAR RNA interaction, we used a crystal structure of TAR RNA with acetylpromazine bound to the bulge of TAR RNA, to dock compounds from Enamine database containing 1.6 million individual compounds. Docking identified 173 compounds that were analyzed for the inhibition of HIV-1 infection. Top ten inhibitory compounds with IC50 ≤ 6 µM were selected and the three least toxic compounds, T6780107 (IC50=2.97 μM), T0516-4834 (IC50=0.2 μM) and T5628834 (IC50=3.46 μM), were further tested for HIV-1 transcription inhibition. Only T0516-4834 compound showed selective inhibition of Tat-induced HIV-1 transcription, whereas T6780107 compound inhibited equally basal and Tat-induced transcription and T5628834 compound only inhibited basal HIV-1 transcription. The T0516-4834 compound also showed strongest inhibition of HIV-1 gag RNA expression and p24 production in CEM T cells infected with HIV-1 IIIB. Of the three compounds, only the T0516-4834 compound disrupted Tat-TAR RNA interaction indicating that it might target TAR RNA. Also, of the three tested compounds, T5628834 but not T6780107 or T0516-4834 disrupted Tat-CDK9/cyclin T1 interaction. Taken together, our study identified novel compound T0516-4834 that disrupted Tat-TAR RNA interaction and inhibited Tat-induced transcription and HIV-1 infection suggesting that this compound might serve as a new lead for anti-HIV-1 therapeutics.

Into the frame of the French TANDEM project (Tsunamis in the Atlantic and the English ChaNnel: Definition of the Effects through numerical Modelling) Principia has been working on the development and qualification of two in-house CFD software’s: the 2D EOLE-SV (Saint Venant) model for simulation of large scale tsunami propagation from the source up to coastal scale and the 3D EOLE-NS (Navier-Stokes) model dedicated to tsunami coastal impact modelling. This paper presents a large range of test cases carried out into the frame of the project and dedicated to the validation of numerical codes in various tsunami wave conditions. The main aspects of phenomena such as wave generation, propagation and coastal impact are investigated on academic situations. A real case simulation is concerned as well, the devastating 2011 Tohoku event which is compared with in-situ data.

The technique of Faraday tomography is a key tool for the study of magnetised plasmas in the new era of broadband radio polarisation observations. In particular, observations at metre-wavelengths provide significantly better Faraday depth accuracies compared to traditional cm-wavelength observations. However, the effect of Faraday depolarisation makes the polarised signal very challenging to detect at metre wavelengths (MHz frequencies). In this work, Faraday tomography is used to characterise the Faraday rotation properties of polarised sources found in data from the LOFAR Two-Metre Sky Survey (LoTSS). Of the 76 extragalactic polarised sources analysed here, we find that all host a radio-loud AGN. The majority of the sources (∼64%) are large FRII radio galaxies with a median projected linear size of 710 kpc and median radio luminosity at 144 MHz of 4 × 10^26 W/Hz. In several cases, both hotspots are detected in polarisation at an angular resolution of ∼20". One such case allowed a study of intergalactic magnetic fields on scales of 3.4 Mpc. Other detected source types include an FRI radio galaxy and at least 8 blazars. Most sources display simple Faraday spectra, however, we highlight one blazar that displays a complex Faraday spectrum, with two close peaks in the Faraday dispersion function.

In this study, a composite flame retardant was created by combining fish scale (FS), fishery waste, and ammonium polyphosphate (APP), a commercially available flame retardant. The composite flame retardant was added to epoxy resin (EP) to form an EP/APP/FS composite that prevents burns and is environmentally friendly. The use of FS conforms to the concept of circular economy and lowers costs by reducing the consumption of APP. Thermogravimetric analysis (TGA), integral procedural decomposition temperature (IPDT), pyrolysis kinetics, limiting oxygen index (LOI), the Underwriters Laboratories 94 (UL94) flammability test, scanning election microscopy, Raman spectroscopy, and energy-dispersive X-ray spectroscopy were used to determine the thermal properties, flame retardant properties, flame retardant mechanism, char morphology, and composition of the composites. The TGA results indicated that the addition of 40% flame retardant raised the char residue from 16.45 wt% (pure EP) to 36.07 wt%, IPDT from 685.6 °C (pure EP) to 1143.1°C, LOI from 21% (pure EP) to 30%, and UL94 classification from fail (pure EP) to V-0. These results suggest an increase in char residue, which indicates better protection of the polymer matrix material. The improvements in IPDT, LOI, and UL94 classification, which indicate greater thermal stability, lower flammability (from flammable to fireproof), and higher flammability rating (from fail to V-0), respectively, suggest that the composite material has favorable thermal properties and is less inflammable.

Accurate prediction of the self-propulsion performance is one of the most important factors for energy-efficient design of a ship. In general, the hydrodynamic performance of a full-scale ship could be achieved by model-scale simulation or towing tank test with extrapolations. With the development of CFD methods and computing power, directly predict ship performance with full-scale CFD is an important approach. In this article, a numerical study on the full-scale self-propulsion performance with propeller operating behind ship at model- and full-scale is presented. The study includes numerical simulations using RANS method with double-model and VOF model respectively and scale effect analysis based on overall performance, local flow fields and detailed vortex identification. Verification study on grid convergence is also performed for full-scale simulation with global and local mesh refinements. And a series of sea trail tests were performed to collect reliable data for the validation of CFD predictions. The analysis of scale effect on hull-propeller interaction shows that the difference on hull boundary layer and flow separation is the main source of scale effect on ship wake. And the results of the fluctuations of propeller thrust and torque along with circulation distribution and local flow field show that propeller’s loading is significantly higher for model-scale ship. It is suggested that the difference on vortex evolution and interaction is more pronounced and have larger effects on ship’s powering performance at model-scale than full-scale according to the simulation results. From the study on self-propulsion prediction, it could be concluded that the simplification on free surface treatment does not only affect the wave-making resistance for bare hull but also the propeller performance and propeller induced ship resistance which can produced up to 5% uncertainty to the power prediction. Roughness is another important factor in full-scale simulation because it has up to approximately 7% effect on the delivery power. As a result of validation study, the numerical simulations of full-scale ship self-propulsion shows good agreement with the sea trail data especially for cases that have considered both roughness and free surface effects. This result will largely enhance our confidence to apply full-scale simulation in the prediction of ship’s self-propulsion performance in the future ship designs.

Back pain is a common symptom that affects all age groups across the globe, when left untreated may eventually lead to disability. A convenient sample selection method was used in this study due to the global Covid-19 pandemic lockdown which was effective in Turkey during the investigation period. Thus, virtual data collection and health education including some health risks were employed. A total population of two hundred adult women was involved in the study but one hundred and twenty-one responses were collected. Findings show that, for socio-demographic characteristics, the pain was found highest in women between the ages of 41-50 and obese/overweight individuals. Although, there was no significant difference recorded in the marital status category. Moreover, statistical mean differences were detected between the scales for ODI (4.18) and BPFS (6.09). Also, p<0.05, paired sample t-test was 0.001 ODI and 0.001 BPFS after the training exercise. This suggests that exercise training is inversely correlated with pain severity which implies that training has a significant influence on pain intensity. Thus, it could be concluded that there is a relationship between the training exercise and ODI/BPFS.

Carton detection is an important technique in the automatic logistics system and can be applied to many applications such as the stacking and unstacking of cartons, the unloading of cartons in the containers. However, there is no public large-scale carton dataset for the research community to train and evaluate the carton detection models up to now, which hinders the development of carton detection. In this paper, we present a large-scale carton dataset named Stacked Carton Dataset (SCD) with the goal of advancing the state-of-the-art in carton detection. Images are collected from the Internet and several warehouses, and objects are labeled using per-instance segmentation for precise localization. There are total of 250,000 instance masks from 16,136 images. Naturelly, a suite of benchmarks are established with several popular detectors. In addition, we design a carton detector based on RetinaNet by embedding our proposed Offset Prediction between Classification and Localization module (OPCL) and Boundary Guided Supervision module (BGS). OPCL alleviates the imbalance problem between classification and localization quality which boosts AP by 3.1%∼4.7% on SCD at the model level while BGS guides the detector to pay more attention to boundary information of cartons and decouple repeated carton textures at the task level. To demonstrate the generalization of OPCL to other datasets, we conduct extensive experiments on MS COCO and PASCAL VOC. The improvements of AP on MS COCO and PASCAL VOC are 1.8%∼2.2% and 3.4%∼4.3% respectively. Source dataset is available here.

This study demonstrates a global, non-parametric, non-iterative optimization of time-mean value of a kind of index vibrated by time-varying forcing. It is based on the fact that the (steady) forced vibration of non-autonomous ordinary differential equation systems is well approximated by an analytical solution when the amplitude of forcing is sufficiently small and its base state without forcing is linearly stable and steady. It is applied to optimize a time-averaged heat-transfer rate on a two-dimensional thermal convection field in a square cavity with horizontal temperature difference, and the globally optimal way of vibrational forcing, i.e. the globally optimal, spatial distribution of vibrational heat and vorticity sources, is first obtained. The maximized vibrational thermal convection corresponds well to the state of internal gravity wave resonance. In contrast, the minimized thermal convection is weak, keeping the boundary layers on both sidewalls thick.

Desmoplastic small round cell tumor (DSRCT) is an extremely rare, aggressive sarcoma affecting adolescents and young adults with male predominance. Generally, it originates from serosal surface of abdominal cavity. The hallmark characteristic of DSRCT is the EWSR1-WT1 gene fusion. This translocation up-regulates the expression of PDGFRα, VEGF and other proteins related to tumor and vascular cell proliferation. Current management of DSRCT includes a combination of chemotherapy, radiation and aggressive cytoreductive surgery plus intra-peritoneal hyperthermic chemotherapy (HIPEC). Despite advances in multimodal therapy, outcomes remain poor since the majority of patients present disease recurrence and die within 3 years. The dismal survival makes DSRCT an orphan disease with urgent need of new drugs. The treatment of advanced and recurrent disease with tyrosine kinase inhibitors, such as pazopanib, sunitinib, and mTOR inhibitors have been evaluated in small studies. Recent works using comprehensive molecular profiling of DSRCT identified potential therapeutic targets. In this review, we aim to describe the current studies conducted to better understand DSRCT biology and to explore the new therapeutic strategies under investigation in preclinical models and in early phase clinical trials.

In a recent Foundations of Physics paper [5] by the current author it was shown that, when the self-force problem of classical electrodynamics is properly solved, it becomes a plausible ontology underlying the statistical description of quantum mechanics. In the current paper we extend this result, showing that ordinary matter, thus represented, possibly suffices in explaining the outstanding observations currently requiring for this task the contrived notions of dark-matter, dark-energy and inflation. The single mandatory 'fix' to classical electrodynamics, demystifying both very small and very large scale physics, should be contrasted with other adhoc solutions to either problems. Instrumental to our cosmological model is scale covariance (and 'spontaneous breaking' thereof), a formal symmetry of classical electrodynamics treated on equal footing with its Poincare covariance, which is incompatible with the (absolute) metrical attributes of the GR metric tensor.

With reference to Planck scale, Mach’s relation, increasing support for large scale cosmic anisotropy and preferred directions and by introducing two new parameters Gamma and Beta, right from the beginning of Planck scale, we make an attempt to estimate ordinary matter density ratio, dark matter density ratio, mass, radius, temperature, age and expansion velocity (from and about the baby universe in all directions). We would like suggest that, from the beginning of Planck scale, 1) Dark matter can be considered as a kind of cosmic foam responsible for formation of galaxies. 2) Cosmic angular velocity is directly proportional to squared cosmic temperature. 3) Ratio of critical temperature to actual temperature plays a heuristic role in understanding ordinary and dark matter density ratios. 4) Cosmic expansion velocity increases with decreasing total matter density ratio. 5) There is no need to consider dark energy for understanding cosmic acceleration.

Growing interest surrounds the assessment of perivascular spaces (PVS) on magnetic resonance imaging (MRI) and their validation as a clinical biomarker of adverse brain health. Nonetheless, the limits of validity of current state-of-the-art segmentation methods are still unclear. Here, we propose an open-source three-dimensional computational framework comprising 3D digital reference objects and evaluate the performance of three PVS filtering methods under various spatiotemporal imaging considerations (including sampling, motion artefacts, and Rician noise). Specifically, we study the performance of the Frangi, Jerman and RORPO filters in enhancing PVS-like structures to facilitate segmentation. Our findings were three-fold. First, as long as voxels are isotropic, RORPO outperforms the other two filters, regardless of imaging quality. Unlike the Frangi and Jerman filters, RORPO’s performance does not deteriorate as PVS volume increases. Second, the performance of all “vesselness” filters is heavily influenced by imaging quality, with sampling and motion artefacts being the most damaging for these types of analyses. Third, none of the filters can distinguish PVS from other hyperintense structures (e.g. white matter hyperintensities, stroke lesions, or lacunes) effectively, the area under precision-recall curve dropped substantially (Frangi: from 94.21 [IQR 91.60, 96.16] to 43.76 [IQR 25.19, 63.38]; Jerman: from 94.51 [IQR 91.90, 95.37] to 58.00 [IQR 35.68, 64.87]; RORPO: from 98.72 [IQR 95.37, 98.96] to 71.87 [IQR 57.21, 76.63] without and with other hyperintense structures, respectively). The use of our computational model enables comparing segmentation methods and identifying their advantages and disadvantages, thereby providing means for testing and optimising pipelines for ongoing and future studies.

Unification point of view, quantum cosmology must be given a priority and one should make a note that, Spin is a basic property of quantum physics and rotation is a very common experience. In this context, we have developed a quantum model of cosmology associated with Machian universe having Planck scale origin, total dark matter, light speed rotation and equality of gravitational self energy density and thermal energy density. We would like to appeal that, observed cosmic radius and age seem to be shortened by 146.3 times their actual magnitudes.

This study addresses the latent construct of attitudes towards environmental conservation based on study participant’s responses. We measured and evaluated the latent scale based on an 18-item scale instrument, over four experimental strata (N=945) in the US Virgin Islands and the Caribbean. We estimated the latent scale reliability and validity. We further fitted multiple alternative two-parameter logistic (2PL) and graded response models (GRM) from Item-Response Theory. We finally constructed and fitted equivalent structural and generalized structural equation models (SEM/GSEM) for the attitudinal latent scale. All scale measures (composite, alpha-based, IRT-based and SEM-based) were consistently and reliably valid measures of the study participants’ latent attitudes toward conservation. We found statistically significant differences among participant’s attributes relating to socio-demographic, physical and core environmental characteristics of participants. We assert that the nature of relationship between cognitive attitudes and individual as well as social behavior related to environmental conservation.

We consider the Dirac electron as a nonperturbative particle-like solution consistent with its own Kerr-Newman (KN) gravitational and electromagnetic field. We develop the earlier models of the KN electron regularized by Israel and López, and consider the non-perturbative electron model as a bag model formed by Higgs mechanism of symmetry breaking. The López regularization determines the unique shape of the electron in the form of a thin disk with a Compton radius reduced by 4π. In our model this disk is coupled with a closed circular string which is placed on the border of the disk and creates the caused by gravitation frame-dragging string tension produced by the vector potential of the Wilson loop. Using remarkable features of the Kerr-Schild coordinate system, which linearizes the Dirac equation, we obtain solutions of the Dirac equation consistent with the KN gravitational and electromagnetic field, and show that this solution takes the form of a massless relativistic string. Parallelism of this model with quantum representations in Heisenberg and Schrodinger pictures explains remarkable properties of the stringy electron model in the relativistic scattering processes.

Fluctuations of protein three-dimensional structures and large-scale conformational transitions are crucial for the biological function of proteins and their complexes. Experimental studies of such phenomena remain very challenging and therefore molecular modeling can be a good alternative or a valuable supporting tool for the investigation of large molecular systems and long-time events. In this mini-review, we present two alternative approaches to the coarse-grained (CG) modeling of dynamic properties of protein systems. We discuss two CG representations of polypeptide chains used for Monte Carlo dynamics simulations of protein local dynamics and conformational transitions and, on other hand, highly simplified structure-based Elastic Network Models of protein flexibility. In contrast to classical Molecular Dynamics the modeling strategies discussed here allow quite accurate modeling of much larger systems and longer time dynamic phenomena. We briefly describe the main features of these models and outline some of their applications, including modeling of near-native structure fluctuations, sampling of large regions of the protein conformational space, or possible support for the structure prediction of large proteins and their complexes.