Miracle-dz/UniFAR-FTUs huggingface dataset:
Explanation and Connectionist Models_final

Introduction Connectionist models are widely used in the cognitive sciences, and well beyond. This is so despite the fact that some critics have charged that we can’t learn about cognition using connectionist models (Fodor and Pylyshyn, 1988). Although researchers who use connectionist models have offered a number of defenses of their methods (Smolensky, 1988; McClelland, 1988), and there is growing empirical evidence suggesting that these models have been successful in advancing cognitive science, there is no consensus on how they work. This chapter explores the epistemic roles played by connectionist models of cognition, and offers a formal analysis of how connectionist models explain.
Morphological and attachment site variations of maxillary labial frenulum

Introduction Maxillary labial frenulum (MLF) is a mucous membrane fold that shows diversity in morphology, position and clinical significance throughout life. The aim of the study was to evaluate different morphological variations and MLF attachment site prevalence in elementary school children. Material and methods the study included 110 children of "Ljutica Bogdan" Primary School in Kalinovik, Bosnia and Herzegovina. Clinical examinations were performed visually under natural light. The upper lip was lightly elevated with the forefingers and thumbs of both hands in horizontal alignment from alveolar ridge. Morphological variations were registered in accordance with Sewerin classification and attachment site according to Placek et al. Results the study included 49 (44.6%) male and 61 (55.4%) female subjects. Mucosal MLF was registered in 57.3%, gingival in 17.3%, papillary in 20.9% and papilla penetrating in 4.5% of examined children. Frenulum simplex was registered in 64.6%, persistent tectolabial frenulum in 4.5%, frenulum with appendix in 9.1%, frenulum with nodule in 14.5%, duplication of frenulum in 5.5%, frenulum with two or more variations was registered in 1.8% of respondents. No difference was observed in morphological variations and attachment site positions between genders. Conclusion Most prevalent MLF morphological type was frenulum simplex and mucosal attachment site. Familiarity with MLF morphology, attachment site position as well as prevalence of different variations is very important in everyday clinical practice from the aspect of proper oral hygiene maintenance, periodontal disease prevention, orthodontic treatment and proper surgical therapy.
Highly Sensitive Cardiac Troponin T Changes and Its Prognostic Value in Patients with Acute Stroke

Background: The Acute ischemic stroke (AIS), which results in the corresponding loss of the neurological function, is characterized by sudden losses in the brain of blood circulation. Cardiac troponins (cTns) are used routinely for diagnosing acute myocardial infarction (AMI), but there is a complex overlap between cardiovascular and cerebrovascular disease. The aim of this study was to evaluate the incidence of Hs-cTnT elevation in acute ischemic stroke population and its prognostic significance. Patients and methods: We enrolled 161 patients admitted with acute ischemic stroke to Menoufia university hospitals and Assalam International hospital. We assessed the full medical history, neurological assessment, National Institutes of Health Stroke Scale (NIHSS), high-sensitive cardiac troponin T (hs-cTnT) level, and ECG on admission and after 24 hours. Statistical analysis was done using R-package for statistical analysis using the appropriate tests. Results: Our results revealed troponin in admission was elevated above >14 ng/dL in 58% of patients. Troponin dynamicity (delta troponin) defined as 25% increase in the admission value was found in 56% of patients. Analyzing ECG changes and echocardiographic findings revealed significant difference between delta troponin group and static troponin group regarding QTc prolongation (p=0.003), T wave changes (p=0.001), ST segment changes (p=0.013), and reduced ejection fraction (p=0.001). Poor outcome defined in our study as modified ranking scale ≥ 3 was found in 48.4% of patients, and good outcome found in 51.6% of patients. Conclusion: The acute Hs-cTnT elevation is high in acute ischemic stroke population, Hs-cTnT dynamicity within 24 hours is common, and delta troponin is correlated with stroke severity and poor outcome.
Comprative Study and Analysis of Object Detection using R-CNN

: Object detection is a field that has been in the limelight a lot in the recent years. Computer vision and image processing are involved in this computer technology and are widely used. Along the path of harnessing the power of vision, numerous algorithms have been found from simple edge detection to pixel level object detection. In this paper we have studied the advancements in object detection algorithms like R-CNN and the latest one being we have studied papers based on types of R-CNN like Fast R-CNN, Faster R-CNN and Mask R-CNN. We have seen their applications in various fields, studied their efficiency, accuracy and limitations.
Some metabolic aspects of dietary thermogenesis

The effect of varying exercise levels on the thermic effect of a mixed nutrient meal was measured in normal young adults. Although exercise was found to potentiate the thermic effect in three subjects there was no consistent effect of exercise in nine other subjects. Blood glucose, serum non-esterified fatty acid, serum glycerol and serum insulin levels were observed before and after the meal. Rate of weight gain, together with metabolic rate before and after a glucose meal, were studied in a group of fifteen female anorexia nervosa patients as their weight was being restored to normal levels. The previously obese anorectic patients gained weight more rapidly, on the sans food intake, than those who were of normal weight before their illness began. The increase in resting metabolic rate (as treatment progressed) was less in the previously obese patients, who also showed a tendency for the metabolic rate to increase less after a glucose meal than the patients with no history of obesity. The thermic effect of glucose was greater in patients with anorexia nervosa than in a comparable control group of six female students. Blood glucose, plasma insulin and plasma glucagon levels were observed before and after a glucose meal in the anorexia nervosa patients. Glucose tolerance was normal in newly admitted emaciated patients, but became impaired as patients were refed and gained weight. Late treatment patients also shaved delayed insulin peaks, high insulin levels and greater insulin resistance. Glucagon levels were high in some patients.
Rectal Dieulafoy’s Lesion: An Underrecognized Cause of Lower Gastrointestinal Bleeding

ABSTRACT Dieulafoy’s lesion is a rare but potentially a life-threatening condition. It accounts for 1%–2% of acute gastrointestinal (GI) bleeding. The lesion is most frequently located in the stomach and may be located anywhere in the alimentary tract. It can be present as severe GI bleeding or chronic GI blood loss. The cause of lesion remains uncertain. The range of clinical presentation varies from acute ill hospitalized patients as well as in the newborn.
Goal-dependent tuning of muscle spindle receptors during movement preparation

Movement preparation tunes muscle stiffness via the goal-dependent control of muscle spindle sensors. Voluntary movements are believed to undergo preparation before they are executed. Preparatory activity can benefit reaction time and the quality of planned movements, but the neural mechanisms at work during preparation are unclear. For example, there are no overt changes in muscle force during preparation. Here, using an instructed-delay manual task, we demonstrate a decrease in human muscle afferent activity (primary spindles) when preparing to reach targets in directions associated with stretch of the spindle-bearing muscle. This goal-dependent modulation of proprioceptors began early after target onset but was markedly stronger at the latter parts of the preparatory period. Moreover, whole-arm perturbations during reach preparation revealed a modulation of stretch reflex gains (shoulder and upper arm muscles) that reflected the observed changes in spindle activity. We suggest that one function of central preparatory activity is to tune muscle stiffness according to task goals via the independent control of muscle spindle sensors.
AI-aided design of novel targeted covalent inhibitors against SARS-CoV-2

The focused drug repurposing of known approved drugs (such as lopinavir/ritonavir) has been reported failed for curing SARS-CoV-2 infected patients. It is urgent to generate new chemical entities against this virus. As a key enzyme in the life-cycle of coronavirus, the 3C-like main protease (3CLpro or Mpro) is the most attractive for antiviral drug design. Based on a recently solved structure (PDB ID: 6LU7), we developed a novel advanced deep Q-learning network with the fragment-based drug design (ADQN-FBDD) for generating potential lead compounds targeting SARS-CoV-2 3CLpro. We obtained a series of derivatives from those lead compounds by our structure-based optimization policy (SBOP). All the 47 lead compounds directly from our AI-model and related derivatives based on SBOP are accessible in our molecular library at https://github.com/tbwxmu/2019-nCov. These compounds can be used as potential candidates for researchers in their development of drugs against SARS-CoV-2.
Theoretical analysis of neural crest cell migration

The neural crest cells are embryonic stem cells that migrate throughout embryos and, at different target locations, give rise to the formation of a variety of tissues and organs. The directional migration of the neural crest cells is experimentally described using a process referred to as contact inhibition of locomotion (CIL), by which cells redirect their movement upon the cell–cell contacts. However, it is unclear how the migration alignment is affected by the motility properties of the cells. Here, we computationally model the migration alignment and the average time to reach a target location as functions of the motility dynamics and interaction of the cells in an open domain with a channel geometry. The results indicate that by varying the properties of the CIL interaction a transition takes place from random movement of the cells to an organized collective migration, where the migration alignment is maximised and the migration time is minimised. This phase transition is accelerated and strengthened with the influx rate of the cells into the domain through increasing the density of the migrating cells. The model further suggests that the migration is more coordinated when the cells with a large CIL radius move fast in a narrow domain.
Distribution and habitat of Australian Pied Oystercatchers Haematopus longirostris along the SE Australian coast

Australian Pied Oystercatchers Haematopus longirostris and their habitat were surveyed on 72 beaches and 674 km of the SE Australian Coast, from Fraser Island, Queensland to near the New South Wales–Victoria state border and between 2015–2018. A grand total of 41 oystercatcher territories and 232 individual birds (the sum of mean beach counts) were counted. Bird-habitat models for oystercatcher mean count density indicated a positive response to the abundance of the primary prey species Donax deltoides, a large ‘surf clam’ and commonly known as the ‘pipi’, a negative response to the proportion of beach length urban and a negative S-N trend. Models for oystercatcher territory density indicated a positive response to pipi abundance and a negative response to pedestrian access density. This report upgrades the coastal development, tourism and human recreation disturbance threats for the species and calls for the long term protection of beach-nesting bird habitat.
Mycobacterium tuberculosis Rv0991c Is a Redox-Regulated Molecular Chaperone

M. tuberculosis infections are responsible for more than 1 million deaths per year. Developing effective strategies to combat this disease requires a greater understanding of M. tuberculosis biology. As in all cells, protein quality control is essential for the viability of M. tuberculosis, which likely faces proteotoxic stress within a host. Here, we identify an M. tuberculosis protein, Ruc, that gains chaperone activity upon oxidation. Ruc represents a previously unrecognized family of redox-regulated chaperones found throughout the bacterial superkingdom. Additionally, we found that oxidized Ruc promotes the protein-folding activity of the essential M. tuberculosis Hsp70 chaperone system. This work contributes to a growing body of evidence that oxidative stress provides a particular strain on cellular protein stability. ABSTRACT The bacterial pathogen Mycobacterium tuberculosis is the leading cause of death by an infectious disease among humans. Here, we describe a previously uncharacterized M. tuberculosis protein, Rv0991c, as a molecular chaperone that is activated by oxidation. Rv0991c has homologs in most bacterial lineages and appears to function analogously to the well-characterized Escherichia coli redox-regulated chaperone Hsp33, despite a dissimilar protein sequence. Rv0991c is transcriptionally coregulated with hsp60 and hsp70 chaperone genes in M. tuberculosis, suggesting that Rv0991c functions with these chaperones in maintaining protein quality control. Supporting this hypothesis, we found that, like oxidized Hsp33, oxidized Rv0991c prevents the aggregation of a model unfolded protein in vitro and promotes its refolding by the M. tuberculosis Hsp70 chaperone system. Furthermore, Rv0991c interacts with DnaK and can associate with many other M. tuberculosis proteins. We therefore propose that Rv0991c, which we named “Ruc” (redox-regulated protein with unstructured C terminus), represents a founding member of a new chaperone family that protects M. tuberculosis and other species from proteotoxicity during oxidative stress. IMPORTANCE M. tuberculosis infections are responsible for more than 1 million deaths per year. Developing effective strategies to combat this disease requires a greater understanding of M. tuberculosis biology. As in all cells, protein quality control is essential for the viability of M. tuberculosis, which likely faces proteotoxic stress within a host. Here, we identify an M. tuberculosis protein, Ruc, that gains chaperone activity upon oxidation. Ruc represents a previously unrecognized family of redox-regulated chaperones found throughout the bacterial superkingdom. Additionally, we found that oxidized Ruc promotes the protein-folding activity of the essential M. tuberculosis Hsp70 chaperone system. This work contributes to a growing body of evidence that oxidative stress provides a particular strain on cellular protein stability.
Full quantum mechanical modeling of the enzyme-substrate system: how laccase detoxifies aflatoxin

This work focuses on: 1) the development of a methodology to perform a full Quantum Mechanics (QM) characterization of enzymatic activity; 2) the development of a rational approach to laccase engineering as a food bioremediator. Aflatoxins are among the most dangerous natural carcinogens, and regularly contaminate reserves of staple crops worldwide. Decontamination of aflatoxin-polluted food is of great interest for ensuring food safety, and bioremediation is regarded as the most promising solution. The fungal isoforms of laccase display the rare potential to detoxify aflatoxin by tackling its aromatic moieties. Yet, because of a generally low efficiency, large-scale application of naturally occurring isoforms has so far been unfeasible. We perform a combination of quantitative experimentation and quantum mechanical modeling on aflatoxin and reveal that: (1) detoxification efficiency is limited by the low enzymatic affinity for the substrate; and (2) aflatoxin is not detoxified by oxidative activity of laccase alone, but requires additional stimulation from the environment. QM modeling also allowed identification of the residues in the laccase tertiary structure that determine affinity of the enzymatic pocket for aflatoxin. We conclude that, for our case-study, a full QM approach is mandatory as a first step towards rational optimization. We detail a feasible approach towards this endeavor and argue that our full QM characterization can serve as a roadmap for enzyme development in other applications pertaining laccase as well as other enzymes.
CO2 reduction driven by a pH gradient

Significance Biology is built of organic molecules, which originate primarily from the reduction of CO2 through several carbon-fixation pathways. Only one of these—the Wood–Ljungdahl acetyl-CoA pathway—is energetically profitable overall and present in both Archaea and Bacteria, making it relevant to studies of the origin of life. We used geologically pertinent, life-like microfluidic pH gradients across freshly deposited Fe(Ni)S precipitates to demonstrate the first step of this pathway: the otherwise unfavorable production of formate (HCOO–) from CO2 and H2. By separating CO2 and H2 into acidic and alkaline conditions—as they would have been in early-Earth alkaline hydrothermal vents—we demonstrate a mild indirect electrochemical mechanism of pH-driven carbon fixation relevant to life’s emergence, industry, and environmental chemistry. All life on Earth is built of organic molecules, so the primordial sources of reduced carbon remain a major open question in studies of the origin of life. A variant of the alkaline-hydrothermal-vent theory for life’s emergence suggests that organics could have been produced by the reduction of CO2 via H2 oxidation, facilitated by geologically sustained pH gradients. The process would be an abiotic analog—and proposed evolutionary predecessor—of the Wood–Ljungdahl acetyl-CoA pathway of modern archaea and bacteria. The first energetic bottleneck of the pathway involves the endergonic reduction of CO2 with H2 to formate (HCOO–), which has proven elusive in mild abiotic settings. Here we show the reduction of CO2 with H2 at room temperature under moderate pressures (1.5 bar), driven by microfluidic pH gradients across inorganic Fe(Ni)S precipitates. Isotopic labeling with 13C confirmed formate production. Separately, deuterium (2H) labeling indicated that electron transfer to CO2 does not occur via direct hydrogenation with H2 but instead, freshly deposited Fe(Ni)S precipitates appear to facilitate electron transfer in an electrochemical-cell mechanism with two distinct half-reactions. Decreasing the pH gradient significantly, removing H2, or eliminating the precipitate yielded no detectable product. Our work demonstrates the feasibility of spatially separated yet electrically coupled geochemical reactions as drivers of otherwise endergonic processes. Beyond corroborating the ability of early-Earth alkaline hydrothermal systems to couple carbon reduction to hydrogen oxidation through biologically relevant mechanisms, these results may also be of significance for industrial and environmental applications, where other redox reactions could be facilitated using similarly mild approaches.
Polygenic adaptation and negative selection across traits, years and environments in a long-lived plant species (Pinus pinaster Ait., Pinaceae)

A decade of association studies in multiple organisms suggests that most complex traits are polygenic; that is, they have a genetic architecture determined by numerous loci distributed across the genome, each with small effect-size. Thus, determining the degree of polygenicity and its variation across traits, environments and years is useful to understand the genetic basis of phenotypic variation. In this study, we applied multilocus approaches to estimate the degree of polygenicity of fitness-related traits in a long-lived plant (Pinus pinaster Ait., maritime pine) and to analyze how polygenicity changes across environments and years. To do so, we evaluated five categories of fitness-related traits (survival, height, phenology-related, functional, and biotic-stress response traits) in a clonal common garden network, planted in contrasted environments (over 12,500 trees). First, most of the analyzed traits showed evidence of local adaptation based on QST-FST comparisons. Second, we observed a remarkably stable degree of polygenicity, averaging 6% (range of 0-27%), across traits, environments and years. As previously suggested for humans, some of these traits showed also evidence of negative selection, which could explain, at least partially, the high degree of polygenicity. The observed genetic architecture of fitness-related traits in maritime pine supports the polygenic adaptation model. Because polygenic adaptation can occur rapidly, our study suggests that current predictions on the capacity of natural forest tree populations to adapt to new environments should be revised, which is of special relevance in the current context of climate change.
Grain aphids (Sitobion avenae) with knockdown resistance (kdr) to insecticide exhibit fitness trade-offs, including increased vulnerability to the natural enemy Aphidius ervi

The development of insecticide-resistance mechanisms in aphids has been associated with inhibitory, pleiotropic fitness costs. Such fitness costs have not yet been examined in the UK’s most damaging cereal aphid, Sitobion avenae (grain aphid) (Hemiptera: Aphididae). This study aimed to evaluate the fitness trade-offs of the insecticide-resistant S. avenae clone versus an insecticide-susceptible S. avenae clone. Additionally, the parasitoid, Aphidius ervi (Hymenoptera: Braconidae), was introduced to examine its potential as a biological control agent. This study found that insecticide-resistant clones had significantly lower population growth and individual relative growth rate. Furthermore, insecticide-resistant clones suffered from a significantly greater rate of parasitisation (mummification) compared to their insecticide-susceptible counterparts. The successfulness of the parasitoid as a biological control agent could prevent the spread of the insecticide-resistant genotype. However, for this to be possible, insecticide spraying regimes need to be moderated, and habitat modification and parasitoid manipulation must be considered.
Dynamic cell wall modifications in brassicas during clubroot disease

Biotic interactions of plants and microbial pathogens can cause drastic changes in cell wall composition in response to developmental reprogramming caused as consequence of an infection. Clubroot disease, caused by the biotrophic plant pathogen Plasmodiophora brassicae (Phytomyxea, Rhizaria), is the economically most important disease of Brassica crops worldwide. The disease is best known by the characteristic hypertrophied roots (root galls, clubroots). Amongst a series of physiological changes of the host tissue, the formation of the characteristic root galls leads to cell wall modification and reorganization. Cell wall chemistry and the hosts genetic repertoire are discussed to play a role in the resilience of plants against clubroot disease. Plant cells infected with P. brassicae are markedly enlarged, and look very differently from uninfected, healthy cells. Here we systematically review cell wall related processes that lead to the typical clubroot phenotype and provide novel insights how P. brassicae uses these modifications to benefit its own development. An infection with P. brassicae impacts on nearly all cell wall related processes, but all alterations are meaningful for successful growth and development of P. brassicae. Processes related to cell wall stability and rigidity (e.g. cellulose, pectin or lignin synthesis) are down-regulated, while cell wall degrading enzymes or processes that increase the flexibility of the host cell wall (e.g. expansin) are up-regulated. The here presented findings indicate that P. brassicae weakens the structural stability of its host cell while it increases its elasticity, which in consequence allows P. brassicae to grow bigger and ultimately to develop more resting spores. Consequently, the understanding of the modification of the host cell wall is important for the formation of the characteristic root galls but also to better understand clubroot disease.