Miracle-dz/UniFAR-FTUs huggingface dataset:
A study of quality improvements by refactoring

Refactorings, behavior preserving transformations, are claimed to make software easier to understand and to improve software design. However, these claimed quality improvements have yet to be validated. This dissertation reports on our contributions to their validation. First, a validation of two existing reengineering patterns that use refactoring to support program comprehension is presented. Second, we discuss the results of formal analysis of the conditions in which known refactorings improve coupling and cohesion as criteria for well-balanced object-oriented design. The results of this research confirm that, indeed, the claimed benefits can occur, and describe how and when the application of refactoring can improve selected quality characteristics. The integration of these results in today's refactoring tools can support maintainers in assessing which refactorings to apply where, ultimately reducing the effort of transforming towards an optimal solution.
Application of Homology Modeling by Enhanced Profile–Profile Alignment and Flexible-Fitting Simulation to Cryo-EM Based Structure Determination

Application of cryo-electron microscopy (cryo-EM) is crucially important for ascertaining the atomic structure of large biomolecules such as ribosomes and protein complexes in membranes. Advances in cryo-EM technology and software have made it possible to obtain data with near-atomic resolution, but the method is still often capable of producing only a density map with up to medium resolution, either partially or entirely. Therefore, bridging the gap separating the density map and the atomic model is necessary. Herein, we propose a methodology for constructing atomic structure models based on cryo-EM maps with low-to-medium resolution. The method is a combination of sensitive and accurate homology modeling using our profile–profile alignment method with a flexible-fitting method using molecular dynamics simulation. As described herein, this study used benchmark applications to evaluate the model constructions of human two-pore channel 2 (one target protein in CASP13 with its structure determined using cryo-EM data) and the overall structure of Enterococcus hirae V-ATPase complex.
Microclimate‐driven trends in spring‐emergence phenology in a temperate reptile (Vipera berus): Evidence for a potential “climate trap”?

Abstract Climate change can not only increase the exposure of organisms to higher temperatures but can also drive phenological shifts that alter their susceptibility to conditions at the onset of breeding cycles. Organisms rely on climatic cues to time annual life cycle events, but the extent to which climate change has altered cue reliability remains unclear. Here, we examined the risk of a “climate trap”—a climatically driven desynchronization of the cues that determine life cycle events and fitness later in the season in a temperate reptile, the European adder (Vipera berus). During the winter, adders hibernate underground, buffered against subzero temperatures, and re‐emerge in the spring to reproduce. We derived annual spring‐emergence trends between 1983 and 2017 from historical observations in Cornwall, UK, and related these trends to the microclimatic conditions that adders experienced. Using a mechanistic microclimate model, we computed below‐ and near‐ground temperatures to derive accumulated degree‐hour and absolute temperature thresholds that predicted annual spring‐emergence timing. Trends in annual‐emergence timing and subsequent exposure to ground frost were then quantified. We found that adders have advanced their phenology toward earlier emergence. Earlier emergence was associated with increased exposure to ground frost and, contradicting the expected effects of macroclimate warming, increased post‐emergence exposure to ground frost at some locations. The susceptibility of adders to this “climate trap” was related to the rate at which frost risk diminishes relative to advancement in phenology, which depends on the seasonality of climate. We emphasize the need to consider exposure to changing microclimatic conditions when forecasting biological impacts of climate change.
Challenges in the Diagnosis of Viral Encephalitis in Children: The Case of Two Siblings

Encephalitis in children may lead to adverse outcomes and long-term neurodevelopmental sequelae. The prompt identification of the causative agent is important to guide proper management in cases with encephalitis; however, the etiology often remains undetermined. The use of polymerase chain reaction (PCR) analysis in the cerebrospinal fluid (CSF) has increased the diagnostic yield in encephalitis cases; however, it may be occasionally misleading. In this article, we describe the case of a male immunocompetent child with encephalitis in which human herpesvirus-7 (HHV-7) was detected in CSF by PCR. As the detection of HHV-7 DNA in the CSF alone is insufficient to prove an etiologic association of severe encephalitis in immunocompetent children, alternative diagnoses were pursued. Enterovirus (E-11) was detected by PCR analysis of the nasopharyngeal and rectal swabs of the male patient. The final diagnosis was facilitated by the findings in his sibling, which presented concurrently with enteroviral encephalitis. Failure to detect enterovirus in the CSF by PCR does not exclude enteroviral encephalitis; screening of other samples, from other body sites, may be necessary to identify the virus, and physicians should take into consideration all evidence, including history, clinical presentation, and sick contacts’ clinical status.
A Critical Review on the Economically Feasible and Sustainable Poly(3-Hydroxybutyrate-co-3-hydroxyvalerate) Production from Alkyl Alcohols

Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (P(3HB-co-3HV)) is the most studied short-chain-length polyhydroxyalkanoates (PHA) with high application importance in various fields. The domination of high-cost propionate and valerate over other 3-hydroxyvalerate (3HV) precursors owing to their wide preference among PHA-producing bacteria has hindered the development of diverse production processes. As alkyl alcohols are mainly produced from inexpensive starting materials through oxo synthesis, they contribute a cost-effective advantage over propionate and valerate. Moreover, alkyl alcohols can be biosynthesized from natural substrates and organic wastes. Despite their great potential, their toxicity to most PHA-producing bacteria has been the major drawback for their wide implementation as 3HV precursors for decades. Although the standard PHA-producing bacteria Cupriavidus necator showed promising alcohol tolerance, the 3HV yield was discouraging. Continuous discovery of alkyl alcohols-utilizing PHA-producing bacteria has enabled broader choices in 3HV precursor selection for diverse P(3HB-co-3HV) production processes with higher economic feasibility. Besides continuous effort in searching for promising wild-type strains, genetic engineering to construct promising recombinant strains based on the understanding of the mechanisms involved in alkyl alcohols toxicity and tolerance is an alternative approach. However, more studies are required for techno-economic assessment to analyze the economic performance of alkyl alcohol-based production compared to that of organic acids.
Therapeutic Effects of Milk Thistle (Silybum marianum L.) and Artichoke (Cynara scolymus L.) on Nonalcoholic Fatty Liver Disease in Type 2 Diabetic Rats

Background At present, nonalcoholic fatty liver disease (NAFLD) does not have an approved pharmacologic therapy. The present study investigated the protective effects and possible mechanisms of milk thistle (Silybum marianum L.) and artichoke (Cynara scolymus L.) in treating NAFLD in type 2 diabetic rats. Methods The NAFLD was established in rats after four weeks of type 2 diabetes induction. The animals were treated with pharmaceutical preparations of milk thistle (Livergol®) and artichoke (Atheromod-B®) extracts for eight weeks. After the end of the intervention, oral glucose tolerance, the serum parameters of oxidative stress, liver functional tests, and lipid profiles were evaluated. Histopathological changes were assessed by hematoxylin and eosin staining. Results Treatment with preparations of milk thistle and artichoke nonsignificantly improved glucose tolerance in diabetic rats. Both preparations significantly improved serum superoxide dismutase activity and the level of malondialdehyde. Although treatment with milk thistle reduced serum activity of aspartate aminotransferase and serum levels of triglyceride (TG), total cholesterol, and low-density lipoprotein-cholesterol, artichoke extracts only attenuated the serum level of TG. Milk thistle also effectively protected the liver from histological changes. Conclusions Milk thistle could be a promising pharmacological option for the treatment of NAFLD. Nonetheless, long-term randomized clinical trials are necessary to confirm the observed results.
Development of a clinician guide for electronic medication adherence products in older adults

Background/objectives: The ability to manage medications independently may be affected in older adults due to physical and cognitive limitations. Numerous electronic medication adherence products (eMAPs) are available to aid medication management. Unfortunately, there are no available guidelines to support clinicians in recommending eMAPs. The objective of this study was to create and validate a clinician tool to guide use of eMAPs. Methods: Pharmacists who previously tested the usability of the eMAPs participated in a focus group to provide feedback on 5 metrics of the clinician guide: unassisted task completion, efficiency, usability, workload and an overall eMAP score. Participants were asked semistructured questions on how they would use the tool to inform recommendations of medication aids to patients. The discussions were audio-recorded and transcribed verbatim and qualitatively analyzed. The clinician guide was modified to reflect feedback. Results: Five pharmacists (80% female, mean years of practice: 15.8) participated in the focus group. The clinician guide was modified by removing 2 metrics and adding an additional 8 metrics: maximum number of alarms, number of days the product can accommodate for based on a daily dosing regimen, price, monthly subscription, portability, locking feature, average time to set the device and number of steps required to set the device. The definition and calculation for unassisted task completion were modified. Additional instructions and specific patient case examples were also included in the final clinician guide. Conclusion: Since significant variability exists between eMAPs, it is imperative to have a tool for frontline clinicians to use when appropriately recommending the use of these products for medication management in older adults.
On numerical prediction of the stability of hypersonic boundary-layer flow over a row of microcavities

This paper is concerned with the structure of steady two–dimensional flow inside the viscous sublayer in hypersonic boundary–layer flow over a flat surface in which microscopic cavities (‘microcavities’) are embedded. Such a so–called Ultra Absorptive Coating (UAC) has been predicted theoretically [1] and demonstrated experimentally [2] to stabilize passively hypersonic boundary–layer flow. In an effort to further quantify the physical mechanism leading to flow stabilization, this paper focuses on the nature of the basic flows developing in the configuration in question. Direct numerical simulations are performed, addressing firstly steady flow inside a singe microcavity, driven by a constant shear, and secondly a model of a UAC surface in which the two–dimensional boundary layer over a flat plate and a minimum nontrivial of two microcavities embedded in the wall are solved in a coupled manner. The influence of flow– and geometric parameters on the obtained solutions is illustrated. Based on the results obtained, the limitations of currently used theoretical methodologies for the description of flow instability are identified and suggestions for the improved prediction of the instability characteristics of UAC surfaces are discussed.Copyright © 2003 by ASME
Mapping Transformation Enabled High-Performance and Low-Energy Memristor-Based DNNs

When deep neural network (DNN) is extensively utilized for edge AI (Artificial Intelligence), for example, the Internet of things (IoT) and autonomous vehicles, it makes CMOS (Complementary Metal Oxide Semiconductor)-based conventional computers suffer from overly large computing loads. Memristor-based devices are emerging as an option to conduct computing in memory for DNNs to make them faster, much more energy efficient, and accurate. Despite having excellent properties, the memristor-based DNNs are yet to be commercially available because of Stuck-At-Fault (SAF) defects. A Mapping Transformation (MT) method is proposed in this paper to mitigate Stuck-at-Fault (SAF) defects from memristor-based DNNs. First, the weight distribution for the VGG8 model with the CIFAR10 dataset is presented and analyzed. Then, the MT method is used for recovering inference accuracies at 0.1% to 50% SAFs with two typical cases, SA1 (Stuck-At-One): SA0 (Stuck-At-Zero) = 5:1 and 1:5, respectively. The experiment results show that the MT method can recover DNNs to their original inference accuracies (90%) when the ratio of SAFs is smaller than 2.5%. Moreover, even when the SAF is in the extreme condition of 50%, it is still highly efficient to recover the inference accuracy to 80% and 21%. What is more, the MT method acts as a regulator to avoid energy and latency overhead generated by SAFs. Finally, the immunity of the MT Method against non-linearity is investigated, and we conclude that the MT method can benefit accuracy, energy, and latency even with high non-linearity LTP = 4 and LTD = −4.
Assessment of Exposure to Di-(2-ethylhexyl) Phthalate (DEHP) Metabolites and Bisphenol A (BPA) and Its Importance for the Prevention of Cardiometabolic Diseases

Exposomics analyses have highlighted the importance of biomonitoring of human exposure to pollutants, even non-persistent, for the prevention of non-communicable diseases such as obesity, diabetes, non-alcoholic fatty liver disease, atherosclerosis, and cardiovascular diseases. Phthalates and bisphenol A (BPA) are endocrine disrupting chemicals (EDCs) widely used in industry and in a large range of daily life products that increase the risk of endocrine and cardiometabolic diseases especially if the exposure starts during childhood. Thus, biomonitoring of exposure to these compounds is important not only in adulthood but also in childhood. This was the goal of the LIFE-PERSUADED project that measured the exposure to phthalates (DEHP metabolites, MEHP, MEHHP, MEOHP) and BPA in Italian mother–children couples of different ages. In this paper we describe the method that was set up for the LIFE PERSUADED project and validated during the proficiency test (ICI/EQUAS) showing that accurate determination of urinary phthalates and BPA can be achieved starting from small sample size (0.5 mL) using two MS techniques applied in cascade on the same deconjugated matrix.
Digestibilidad ileal estandarizada de la proteína y aminoácidos de la pasta de ajonjolí en cerdos en crecimiento

Para determinar la digestibilidad ileal aparente (DIA) y estandarizada (DIE) de los aminoácidos de pasta de ajonjolí (PA), se utilizaron 10 cerdos de 78.6 ± 5.2 kg, alojados en jaulas metabólicas; localizadas en una sala con temperatura controlada (19 a 22 °C). A los cerdos se les implantó una cánula “T” en íleon y se alimentaron dos veces al día, a 2.5 veces su requerimiento de energía digestible de mantenimiento (110 kcal por kg de PV0.75). Se elaboraron dos dietas con 160 g de PC/kg de alimento: una con PA y otra con pasta de soya (PS). Los resultados muestran que la DIA de los siguientes aminoácidos fue superior en la PA que en la PS: arginina (P<0.0001) 7.3 unidades; alanina, ácido glutámico, glicina, metionina y valina fue en promedio 6.8 unidades mayor (P<0.01); cisteína fue mayor en 11.5 unidades (P <0.05). Contrariamente la DIA de prolina (P<0.0001), leucina (P<0.01) y lisina (P<0.05) fueron inferiores en 21.9, 2.8 y 2.5 unidades respectivamente en la PA que en la PS. La DIE de arginina (P<0.0001) fue 6.7 % superior; valina (P<0.001) 10.6 % mayor, alanina, ácido glutámico, glicina y treonina (P<0.01) fue superior en promedio en 6.4 %; y de cisteína, histidina, isoleucina, y tirosina (P<0.05) fue superior en 7.45 % en la PA que en la PS. La DIE de prolina (P<0.01) y leucina (P<0.05) fueron inferiores en 4.7 y 2.1 en la PA que en PS. Se concluye que la PA es una buena fuente de aminoácidos digestibles para la alimentación del cerdo.
The Development of Digital Finance and Financing Constraints of Small and Medium-sized Enterprises

As a part of the national economy, Small and Medium-sized enterprises play a role in promoting a country's economy, but most studies show that financing constraints hinder the innovation and development of small and Medium-sized enterprises. This paper analyzed the effect of descriptive statistics, robustness test, and heterogeneity analysis to explore the impact of digital financial development on small and Medium-sized enterprises' financing constraints. Research shows that with the increase of the digital finance index, financing constraint tends to decrease. Therefore, the development of digital finance plays a positive role in the financing constraints of small and Medium-sized enterprises.
Integrated Missile Guidance and Control Three-channel Decoupling Design Method

Based on extended state observer(ESO)and backstepping-sliding mode design method,a novel integrated guidance and control three-channel decoupling design approach is proposed for the problem that a homing missile attacks ground target during diving phase.The fully integrated guidance and control model is established by combining guidance and control system in addition to considering interaction between three channels in control system.ESOs are adopted to estimate and compensate dynamic coupling terms and uncertainties currently in six degrees of freedom(6DOF)system,which realizes the active decoupling between each channel in the system,thereby generating three-channel decoupling control law for integrated missile guidance and control based on ESO.Meanwhile,in order to solve the problem that high order nonlinear system can cause"computation explosion"according to using ESO to measure state values,the adaptive control law is employed to afford redress for observation error in ESO.It is demonstrated that all states in the closed loop system are ultimately bounded on account of Lyapunov stability theorem.Compared with three-channel independent design method for integrated system and traditional guidance and control system design method,the simulation results verify the advantages and practicalities of the integrated guidance and control decoupling design algorithm based on ESO.
Assessment of Five Pesticides as Endocrine-Disrupting Chemicals: Effects on Estrogen Receptors and Aromatase

Pesticides are widely applied all over the world, and pesticide exposure can induce different biological effects posing a possible threat to human health. Due to their effects on the endocrine system, some pesticides are classified as endocrine disruptors. The aim of the study is to assess the interference of five pesticides on estrogen biosynthesis and estrogen signaling. Three neonicotinoid insecticides (Acetamiprid, Clothianidin, and Thiamethoxam), a carbamate insecticide (Methiocarb) and a herbicide (Oxadiazon) were tested. The effect of pesticides on estrogen biosynthesis was studied through an ELISA assay using a recombinant form of human aromatase, the enzyme that catalyzes the transformation of androgens to estrogens. Moreover, the effect of pesticides on estrogen signaling was assessed using a gene reporter assay on MELN cells, which measures estrogen receptor-mediated estrogenic activity. The results of the ELISA assay showed that the pesticides did not alter aromatase activity (no interference with estrogen biosynthesis), while the results of the gene reporter assay showed that only Methiocarb was able to alter estrogen signaling at high doses. The estrogenic activity of Methiocarb, expressed as 17β-estradiol equivalency factor (EEF), was equal to 8.0 × 10−8. In conclusion, this study suggested that Methiocarb should be considered a potential endocrine disruptor.
Essential Oil of Cannabis sativa L: Comparison of Yield and Chemical Composition of 11 Hemp Genotypes

Cannabis sativa L. is an annual species cultivated since antiquity for different purposes. While, in the past, hemp inflorescences were considered crop residues, at present, they are regarded as valuable raw materials with different applications, among which extraction of the essential oil (EO) has gained increasing interest in many fields. The aim of the present study is the evaluation of the yield and the chemical composition of the EO obtained by hydrodistillation from eleven hemp genotypes, cultivated in the same location for two consecutive growing seasons. The composition of the EOs was analyzed by GC–MS, and then subjected to multivariate statistical analysis. Sesquiterpenes represented the main class of compounds in all the EOs, both in their hydrocarbon and oxygenated forms, with relative abundances ranging from 47.1 to 78.5%; the only exception was the Felina 32 sample collected in 2019, in which cannabinoids predominated. Cannabinoids were the second most abundant class of compounds, of which cannabidiol was the main one, with relative abundances between 11.8 and 51.5%. The statistical distribution of the samples, performed on the complete chemical composition of the EOs, evidenced a partition based on the year of cultivation, rather than on the genotype, with the exception of Uso-31. Regarding the extraction yield, a significant variation was evidenced among both the genotypes and the years of cultivation.
Tea Polyphenols Prevent and Intervene in COVID-19 through Intestinal Microbiota

Although all countries have taken corresponding measures, the coronavirus disease 2019 (COVID-19) is still ravaging the world. To consolidate the existing anti-epidemic results and further strengthen the prevention and control measures against the new coronavirus, we are now actively pioneering a novel research idea of regulating the intestinal microbiota through tea polyphenols for reference. Although studies have long revealed the regulatory effect of tea polyphenols on the intestinal microbiota to various gastrointestinal inflammations, little is known about the prevention and intervention of COVID-19. This review summarizes the possible mechanism of the influence of tea polyphenols on COVID-19 mediated by the intestinal microbiota. In this review, the latest studies of tea polyphenols exhibiting their own antibacterial and anti-inflammatory activities and protective effects on the intestinal mucosal barrier are combed through and summarized. Among them, (−)-epigallocatechin-3-gallate (EGCG), one of the main monomers of catechins, may be activated as nuclear factor erythroid 2 p45-related factor 2 (Nrf2). The agent inhibits the expression of ACE2 (a cellular receptor for SARS-CoV-2) and TMPRSS2 to inhibit SARS-CoV-2 infection, inhibiting the life cycle of SARS-CoV-2. Thus, preliminary reasoning and judgments have been made about the possible mechanism of the effect of tea polyphenols on the COVID-19 control and prevention mediated by the microbiota. These results may be of great significance to the future exploration of specialized research in this field.