פרסומים

BACKGROUND: Nearly a year into the COVID-19 pandemic, we still lack effective anti-SARS-CoV-2 drugs with substantial impact on mortality rates except for dexamethasone. As the search for effective antiviral agents continues, we aimed to review data on the potential of repurposing antiparasitic drugs against viruses in general, with an emphasis on coronaviruses. METHODS: We performed a review by screening in vitro and in vivo studies that assessed the antiviral activity of several antiparasitic agents: chloroquine, hydroxychloroquine (HCQ), mefloquine, artemisinins, ivermectin, nitazoxanide (NTZ), niclosamide, atovaquone and albendazole. RESULTS: For HCQ and chloroquine we found ample in vitro evidence of antiviral activity. Cohort studies that assessed the use of HCQ for COVID-19 reported conflicting results, but randomized controlled trials (RCTs) demonstrated no effect on mortality rates and no substantial clinical benefits of HCQ used either for prevention or treatment of COVID-19. We found two clinical studies of artemisinins and two studies of NTZ for treatment of viruses other than COVID-19, all of which showed mixed results. Ivermectin was evaluated in one RCT and few observational studies, demonstrating conflicting results. As the level of evidence of these data is low, the efficacy of ivermectin against COVID-19 remains to be proven. For chloroquine, HCQ, mefloquine, artemisinins, ivermectin, NTZ and niclosamide, we found in vitro studies showing some effects against a wide array of viruses. We found no relevant studies for atovaquone and albendazole. CONCLUSIONS: As the search for an effective drug active against SARS-CoV-2 continues, we argue that pre-clinical research of possible antiviral effects of compounds that could have antiviral activity should be conducted. Clinical studies should be conducted when sufficient in vitro evidence exists, and drugs should be introduced into widespread clinical use only after being rigorously tested in RCTs. Such a search may prove beneficial in this pandemic or in outbreaks yet to come.

Accurately describing excited states within Kohn–Sham (KS) density functional theory (DFT), particularly those which induce ionization and charge transfer, remains a great challenge. Common exchange-correlation (xc) approximations are unreliable for excited states

owing, in part, to the absence of a derivative discontinuity in the xc energy (Δ), which relates a many-electron energy difference to the corresponding KS energy difference. We demonstrate, analytically and numerically, how the relationship between KS and many-electron energies leads to the step structures observed in the exact xc potential in four scenarios: electron addition, molecular dissociation, excitation of a finite system, and charge transfer. We further show that steps in the potential can be obtained also with common xc approximations, as simple as the LDA, when addressed from the ensemble perspective. The article therefore highlights how capturing the relationship between KS and many-electron energies with advanced xc approximations is crucial for accurately calculating excitations, as well as the ground-state density and energy of systems which consist of distinct subsystems. Publisher's version       arXiv version

 

The minimalist approach that we develop here is a framework that allows to appreciate how non-conscious processing and conscious contents shape human cognition, broadly defined. It is composed of three simple principles. First, cognitive processes are inherently non-conscious, while their inputs and (interim) outputs may be consciously experienced. Second, non-conscious processes and elements of the cognitive architecture prioritize information for conscious experiences. Third, conscious events are composed of series of conscious contents and non-conscious processes, with increased duration leading to more opportunity for processing. The narrowness of conscious experiences is conceptualized here as a solution to the problem of channeling the plethora of non-conscious processes into action and communication processes that are largely serial. The framework highlights the importance of prioritization for consciousness, and we provide an illustrative review of three main factors that shape prioritization—stimulus strength, motivational relevance and mental accessibility. We further discuss when and how this framework (i) is compatible with previous theories, (ii) enables new understandings of established findings and models, and (iii) generates new predictions and understandings.

Meandering channels and valleys are dominant landscape features on Earth. Their morphology and remnants potentially indicate past base-level fluctuations and changing regional slopes. The prevailing presence of meandering segments in low-slope areas somewhat confuses the physically based relationships between slope and channel meandering. This relationship underlies a fundamental debate: do incised sinuous channels actively develop during steepening of a regional slope, or do they inherit the planform of a preexisting sinuous channel through vertical incision? This question was previously explored through reconstructed evolution of meandering rivers, numerical simulations, and controlled, scaled-down laboratory experiments. Here, we study a rare, field-scale set of a dozen adjacent perennial channels, evolving in recent decades in a homogeneous erodible substrate in response to the Dead Sea level fall (> 30 m over 40 years). These channels are fed by perennial springs and have no drainage basin or previous fluvial history; they initiated straight and transformed into incising meandering channels following the emergence of the preexisting lake bathymetry, which resulted in increased channel lengths and regional slopes at different rates for each channel. This field setting allows testing the impact of changing regional slope on the sinuosity of a stream in the following cases: (a) relatively long and low-gradient shelf-like margins, (b) a sharp increase in the basinward gradient at the shelf-slope transition, and (c) gradually steepening slopes. Under a stable and low valley slope, the channels mainly incise vertically, inheriting a preexisting sinuous pattern. When the regional slope steepens, the channels start to meander, accompanying the vertical incision. The highest sinuosity evolved in the steepest channel, which also developed the deepest and widest valley. These results emphasize the amplifying impact of steepening regional slope on sinuosity. This holds when the flow is confined and chute cutoffs are scarce.

This study compares the argumentative writing characteristics of students from different sociocultural backgrounds. We focused on Jewish ultra-Orthodox (Haredi) students, educated in a segregated religious school for boys (yeshiva), who are now attempting to integrate in secular higher education in Israel. To better understand the unique characteristics of this population, we reviewed 92 essays written by Haredi students, and compared them with 76 essays by public education (PE) graduates. Our analysis was based on the cognitive and sociocultural perspectives of argumentation. Both bottom-up and top-down criteria were used to elicit the argumentative writing characteristics either emerging from the data or based on existing theories. Our primary findings indicate that Haredi students have distinct argumentative characteristics, including the use of more complex and dialectic arguments and unique persuasive tactics. These findings are discussed in light of previous research on yeshiva learning methods and recommendations are provided for adjusting the existing higher education curricula to suit both PE and Haredi students.

Facilitating the uptake of established methodologies for risk-based decision-making in product conformity assessment taking into account measurement uncertainty by providing dedicated software is the aim of the European project EMPIR CASoft(2018–2020), involving the National Measurement Institutes from France, Sweden and the UK, and industrial partner Trescal (FR) as primary supporter. The freely available software helps end-users perform the required risk calculations in accordance with current practice and regulations and extends that current practice to include bivariate cases. The software is also aimed at supporting testing and calibration laboratories in the application of the latest version of the ISO/IEC 17025:2017 standard, which requires that``…the laboratory shall document the decision rule employed, taking into account the level of risk […] associated with the decision rule and apply the decision rule.'' Initial experiences following launch of the new software in Spring 2020 are reported.

Three-dimensional printing (3DP) is considered among the key-technologies for the next industrial revolution, with considerable effects on production processes, economy, and society. In this context, the most relevant part of the market consists of polymeric 3D printing. The 3D printable liquids are composed of various components, among them dyes are usually underrated because they are introduced merely for aesthetical reasons or to enhance the objects' resolution. In recent years, the capability of specific dyes to go beyond conventional use and to confer functional properties to 3D printed objects has become an emerging research area. Modifying elastic moduli upon light irradiation, inducing optical and emitting properties in the matrices or conferring temperature responsivity are just few examples of innovative stimuli-responsive materials that can be produced by combining well-designed dyes with the appropriate 3DP printed matrices. In this Review, we discuss and critically analyze the most relevant recent results achieved in the use of smart dyes in the synthesis of stimuli responsive 3D printed polymers.

Summary The recent years have witnessed the emergence of high-throughput phenotyping techniques. In particular, these techniques can characterize a comprehensive landscape of physiological traits of plants responding to dynamic changes in the environment. These innovations, along with the next-generation genomic technologies, have brought plant science into the big-data era. However, a general framework that links multifaceted physiological traits to DNA variants is still lacking. Here, we developed a general framework that integrates functional physiological phenotyping (FPP) with functional mapping (FM). This integration, implemented with high-dimensional statistical reasoning, can aid in our understanding of how genotype is translated toward phenotype. As a demonstration of method, we implemented the transpiration and soil-plant-atmosphere measurements of a tomato introgression line population into the FPP-FM framework, facilitating the identification of quantitative trait loci (QTLs) that mediate the spatiotemporal change of transpiration rate and the test of how these QTLs control, through their interaction networks, phenotypic plasticity under drought stress.

BACKGROUND: Contrasting historical views represent the asylum as a manifestation of humanitarian and therapeutic progress or as an institution of social control designed to bolster the capitalist economic order. More extreme critics suggest it was used to incarcerate people exhibiting only political or social deviance. METHODS: Case notes of 200 consecutive male and female admissions to the Essex County Asylum in 1904 were inspected. The nature of presentations was classified in contemporary terms into broad categories of disorder. Outcomes were identified and differences between men and women were explored. RESULTS: We found no evidence that patients were admitted without signs of significant mental and behavioural disturbance. In total, 44% of admissions had signs of an organic condition, and these were more frequent among men. Women were admitted at a faster rate and were 1.6 times more likely to have mania or a psychotic disorder. Overall, 45.5% of patients were discharged, with 62% of patients with non-organic disorders discharged recovered or improved. CONCLUSIONS: Evidence partially supports both views of the asylum. In line with other studies, there is no evidence that the asylum was used to incarcerate people who did not show significant signs of disorder, but it did provide care and containment for those who could not be accommodated elsewhere, including many with organic conditions. The asylum also had a therapeutic orientation, however, and encouraged discharge where possible. In contrast to some other studies, women were more likely to be institutionalised than men, possibly reflecting their greater economic dependency.

-mediated IPSCs in VTA DA neurons from both inhibitory sources. Furthermore, exogenous light activation of both RMTg and NAc afferents in the VTA during the acquisition of cocaine-CPP significantly reduced the rewarding properties of cocaine. This behavioral observation was correlated with the reduction in the neuronal activity of VTA DA neurons as measured by the expression of c-fos. Together, these results emphasize the critical role of these GABAergic inputs to the VTA in modulating and potentially interrupting cocaine reward.

Elevated dopamine (DA) levels in the reward system underlie various drug-related behaviors, including addiction. As a major DA source in the reward system, the ventral tegmental area (VTA) is highly regulated by GABAergic inputs projected from different brain regions. It was previously shown that cocaine exposure reduces GABAA-mediated inhibitory postsynaptic currents (IPSCs) in VTA DA neurons; however, the specific GABAergic input underlying this inhibitory effect remains unknown. Here, using optogenetics, we separately activate and characterize different GABAergic afferents innervating the VTA, focusing on the rostromedial tegmental nucleus (RMTg) and the nucleus accumbens (NAc). GABAA-mediated IPSCs were recorded from VTA DA neurons, and the effect of DA-induced inhibition was measured in an afferent-specific manner. In addition, to examine the effect of enhanced GABAergic tone on the rewarding properties of cocaine, we exogenously activated the different GABAergic inputs during the acquisition phase of cocaine conditioned place preference (CPP). We found that acute cocaine exposure strongly attenuates GABAA-mediated IPSCs in VTA DA neurons from both inhibitory sources. Furthermore, exogenous light activation of both RMTg and NAc afferents in the VTA during the acquisition of cocaine-CPP significantly reduced the rewarding properties of cocaine. This behavioral observation was correlated with the reduction in the neuronal activity of VTA DA neurons as measured by the expression of c-fos. Together, these results emphasize the critical role of these GABAergic inputs to the VTA in modulating and potentially interrupting cocaine reward.

In analytical chemistry, spectral imaging of complex analytical systems is commonly performed. A major task in spectral imaging analysis is to extract signals related to important analytes present in the imaged scene. Hence, the first task of spectral image analysis is to perform an image segmentation to extract the relevant signals to analyze. However, in the chemometric domain, the traditional image segmentation methods are limited either to threshold-based or pixel-wise classification, therefore, no approache uses the contextual information present in the imaging scene. This study presents for the first time a pixel2pixel (p2p) image translation using conditional generative adversarial networks (cGAN) for the segmentation of spectral images. The p2p cGAN trains two neural models simultaneously where one model (generator) learns to segment and the other model learns to detect if the segmentation performed by the generator model is correct. During the process of generation and detection, the model automatically learns to segment the spectral images accurately. As an application of the p2p cGAN, a case of segmenting visible and near-infrared spectral images of plants was presented. Furthermore, as a comparison, threshold-based and pixel-wise image classification based on partial least-square discriminant analysis were also presented. The results showed that the p2p cGAN based image translation performed the best segmentation task with an intersection over union score of 0.95 ​± ​0.04. The advanced new DL based image processing approaches can complement spectral image processing.