Miracle-dz/UniFAR-FTUs huggingface dataset:
The Rab Interacting Lysosomal Protein (RILP) Homology Domain Functions as a Novel Effector Domain for Small GTPase Rab36

Background: Rab36 is an uncharacterized small GTPase that is largely conserved in vertebrates. Results: RILP family members and JIP3/4 contain a conserved RILP homology domain (RHD) that functions as an effector domain of Rab36. Conclusion: RILP functions as a Rab36 effector that mediates retrograde melanosome transport in melanocytes. Significance: Rab36 may regulate movements of Rab36-bearing vesicles/organelles through interaction with RHD-containing proteins. Small GTPase Rab functions as a molecular switch that drives membrane trafficking through specific interaction with its effector molecule. Thus, identification of its specific effector domain is crucial to revealing the molecular mechanism that underlies Rab-mediated membrane trafficking. Because of the large numbers of Rab isoforms in higher eukaryotes, however, the effector domains of most of the vertebrate- or mammalian-specific Rabs have yet to be determined. In this study we screened for effector molecules of Rab36, a previously uncharacterized Rab isoform that is largely conserved in vertebrates, and we succeeded in identifying nine Rab36-binding proteins, including RILP (Rab interacting lysosomal protein) family members. Sequence comparison revealed that five of nine Rab36-binding proteins, i.e. RILP, RILP-L1, RILP-L2, and JIP3/4, contain a conserved coiled-coil domain. We identified the coiled-coil domain as a RILP homology domain (RHD) and characterized it as a common Rab36-binding site. Site-directed mutagenesis of the RHD of RILP revealed the different contributions by amino acids in the RHD to binding activity toward Rab7 and Rab36. Expression of RILP in melanocytes, but not expression of its Rab36 binding-deficient mutants, induced perinuclear aggregation of melanosomes, and this effect was clearly attenuated by knockdown of endogenous Rab36 protein. Moreover, knockdown of Rab36 in Rab27A-deficient melanocytes, which normally exhibit perinuclear melanosome aggregation because of increased retrograde melanosome transport activity, caused dispersion of melanosomes from the perinucleus to the cell periphery, but knockdown of Rab7 did not. Our findings indicated that Rab36 mediates retrograde melanosome transport in melanocytes through interaction with RILP.
Stability Verification of the Effects of Stem Determination and Earliness of Flowering on Green Stem Disorder of Soybean against Genetic Background and Environment

Abstract Green stem disorder (GSD) of soybean reduces harvesting efficiency and negatively impacts seed appearance when mechanical harvesting is employed. Two recombinant inbred populations were investigated for the effects of segregating stem determination and flowering time on GSD at two different locations, Kyoto and Akita, over two years. Although the severity of GSD of each line varied considerably with the location, the scores showed significant correlation with the environment. Quantitative trait locus (QTL) analysis revealed a strong and consistent QTL for GSD severity in one population of recombinantinbred lines (RILs) across the environments at the Dt1 locus, which governs stem growth habits, and the determinate growth genotypes showed evident symptoms of GSD. However, QTLs were not detected near the Dt1 locus in the other population. Thus, it was unclear if the responsible gene was identical to the stem determination gene. The early flowering genotype showed a more severe symptom of GSD in both populations, but this effect was dependent on theallele at the Dt1 locus. The effect of another QTL detected in the latter population also depended on theallele at the Dt1 locus. Our results indicated that the genetic factor at the Dt1 locusand the factor controlling flowering time influenced the severity of GSD at each location and year and that their effects and interaction complicated the genetic control of the occurrence of GSD.
An Introduction to Infectious Disease Modelling

Preface Abbreviations and Glossary 1. Introduction: the basics - infections, transmission and models 2. How are models set up? I. An introduction to difference equations 3. How are models set up? II. An introduction to differential equations 4. What do models tell us about the dynamics of infections? 5. Age patterns 6. An introduction to stochastic modelling 7. How do models deal with contact patterns? 8. Sexually transmitted infections 9. Special topics in infectious disease modelling Appendix Basic maths Further reading Useful equations
Absence of ice‐cream interference with the adsorption of paracetamol onto activated charcoal

Aims: To measure the extent to which the addition of ice-cream to activated charcoal interferes with its ability to adsorb paracetamol. Method: Activated charcoal, ice-cream and both charcoal and ice-cream were added to stock solutions of paracetamol at both simulated gastric and intestinal pH at charcoal : paracetamol ratios of 3:1, 5:1 and 10:1. The samples were centrifuged and the supernatant assayed for paracetamol concentration. Results: When the charcoal : paracetamol ratio was 3:1, charcoal alone adsorbed 65% of the available paracetamol, and charcoal with ice-cream adsorbed 57%. When the ratio was 5:1, charcoal alone adsorbed 92% of the available paracetamol and charcoal with ice-cream 90%. When the ratio was 10:1, charcoal alone adsorbed 100% of the available paracetamol and charcoal with ice-cream 99%. The results were independent of pH. Conclusions: The practice of adding ice-cream to activated charcoal to improve palatability does not decrease the ability of the charcoal to adsorb paracetamol in vitro, especially if charcoal : drug ratios are above 5:1.
Statistical Analysis of Cost-Effectiveness Data

Preface. 1. Concepts. 1.1 Introduction. 1.2 Cost-effectiveness data and the parameters of interest. 1.3 The cost-effectiveness plane, the ICER and INB. 1.4 Outline. 2. Parameter Estimation for Non-censored Data. 2.1 Introduction. 2.2 Cost. 2.3 Effectiveness. 2.4 Summary. 3. Parameter Estimation for Censored Data. 3.1 Introduction. 3.2 Mean Cost. 3.3 Effectiveness. 3.4 Summary. 4. Cost-effectiveness Analysis. 4.1 Introduction. 4.2 Incremental cost-effectiveness ratio. 4.3 Incremental net benefit. 4.4 The cost-effectiveness acceptability curve. 4.5 Using bootstrap methods. 4.6 A Bayesian incremental net benefit approach. 4.7 Kinked thresholds. 4.8 Summary. 5. Cost-effectiveness Analysis: Examples. 5.1 Introduction. 5.2 The CADET-Hp trial. 5.3 Symptomatic hormone-resistant prostate cancer. 5.4 The Canadian implantable defibrillator study (CIDS). 5.5 The EVALUATE trial. 5.6 Bayesian approach applied to the UK PDS study. 5.7 Summary. 6. Power and Sample Size Determination. 6.1 Introduction. 6.2 Approaches based on the cost-effectiveness plane. 6.3 The classical approach based on net benefit. 6.4 Bayesian take on the classical approach. 6.5 The value of information approach. 6.6 Summary. 7. Covariate Adjustment and Sub-group Analysis. 7.1 Introduction. 7.2 Non-censored data. 7.3 Censored data. 7.4 Summary. 8. Multicenter and Multinational Trials. 8.1 Introduction. 8.2 Background to multinational cost-effectiveness. 8.3 Fixed effect approaches. 8.4 Random effects approaches. 8.5 Summary. 9. Modeling Cost-effectiveness. 9.1 Introduction. 9.2 A general framework for modeling cost-effectiveness results. 9.3 Case study: an economic appraisal of the goal study. 9.4 Summary. References. Author Index. Subject Index. Series List.
GEOGRAPHIC VARIATION, HYBRIDIZATION, AND THE LEAPFROG PATTERN OF EVOLUTION IN THE SUIRIRI FLYCATCHER (SUIRIRI SUIRIRI) COMPLEX

Abstract The Suiriri Flycatcher (Suiriri suiriri) of South America is represented by three distinct forms occurring in parapatry: (1) S. s. suiriri to the southwest in the Chaco/Pampas; (2) S. s. affinis located centrally in the Cerrado/southern Amazonia; and (3) S. s. bahiae to the northeast in the Caatinga. On the basis of an analysis of 366 specimens of S. suiriri, I found meager evidence for long-distance migration, little support for Bergmann's rule, and more support for Gloger's rule. I postulate that an ancestral population of S. suiriri split into three isolated populations, with the central population differentiating most rapidly into affinis, thus explaining the leapfrog pattern of greater similarity between peripheral suiriri and bahiae. After secondary contact, affinis freely hybridized with nominate suiriri in a hybrid zone to the southwest, where specimens demonstrate morphometric intermediacy and increased plumage variability; the rarity of parental phenotypes within the hybrid zone suggests that the two forms are conspecific according to the biological species concept. In the northeast, affinis may have hybridized with a remnant population of suiriri, possibly represented by poorly known bahiae. The intermediate size and increased plumage variability of bahiae resemble that of suiriri × affinis hybrids, supporting a hypothesis of hybrid origin for bahiae, but alternative hypotheses cannot be ruled out. This hypothesis of differentiation is supported by the concordant patterns of disjunction among several pairs of sister taxa of bird species that occur in the Chaco and Caatinga, with no intervening populations in the Cerrado, implying a shared historical process of vicariance. Genetic and behavioral studies are needed to elucidate further the status and history of differentiation within S. suiriri.
Rain Damage on Three Strawberry Cultivars Grown in Subtropical Queensland

In Queensland, Australia, strawberry (Fragaria × ananassa Duchesne) is grown in open fields and rainfall events can damage fruit. Following a rain event, damage was evaluated on three commercial cultivars. ‘Rubygem’ (80%) had more fruit damaged than ‘Strawberry Festival’ (55%) and ‘Camarosa’ (61%). “Etch,” where the surface of the fruit is eroded and, consequently, the seeds are raised relative to the damaged surface, was the most frequently occurring (>80%) damage type and was distributed on the body and tip of the fruit, while some fruit (<16%) showed cracking. Fully mature fruit was damaged (>80%) more than partially mature fruit, which differed between ‘Strawberry Festival’ (16%) and ‘Rubygem’ (68%). Cultivars that are resistant to rain damage would reduce losses and lower risk for the growers.
A Genome-Scan Method to Identify Selected Loci Appropriate for Both Dominant and Codominant Markers: A Bayesian Perspective

Identifying loci under natural selection from genomic surveys is of great interest in different research areas. Commonly used methods to separate neutral effects from adaptive effects are based on locus-specific population differentiation coefficients to identify outliers. Here we extend such an approach to estimate directly the probability that each locus is subject to selection using a Bayesian method. We also extend it to allow the use of dominant markers like AFLPs. It has been shown that this model is robust to complex demographic scenarios for neutral genetic differentiation. Here we show that the inclusion of isolated populations that underwent a strong bottleneck can lead to a high rate of false positives. Nevertheless, we demonstrate that it is possible to avoid them by carefully choosing the populations that should be included in the analysis. We analyze two previously published data sets: a human data set of codominant markers and a Littorina saxatilis data set of dominant markers. We also perform a detailed sensitivity study to compare the power of the method using amplified fragment length polymorphism (AFLP), SNP, and microsatellite markers. The method has been implemented in a new software available at our website (http://www-leca.ujf-grenoble.fr/logiciels.htm).
Configurable Consistency for Wide-Area Caching

Data caching is a well-understood technique for improving the performance and availability of wide area distributed applications. The complexity of caching algorithms motivates the need for reusable middleware support to manage caching. To support diverse data sharing needs effectively, a caching middleware must provide a flexible consistency solution that (i) allows applications to express a broad variety of consistency needs, (ii) enforces consistency efficiently among WAN replicas satisfying those needs, and (iii) employs application-independent mechanisms that facilitate reuse. Existing replication solutions either target specific sharing needs and lack flexibility, or leave significant consistency management burden on the application programmer. As a result, they cannot offload the complexity of caching effectively from a broad set of applications. In this dissertation, we show that a small set of customizable data coherence mechanisms can support wide-area replication effectively for distributed services with very diverse consistency requirements. Specifically, we present a novel flexible consistency framework called configurable consistency that enables a single middleware to effectively support three important classes of applications, namely, file sharing, shared database and directory services, and real-time collaboration. Instead of providing a few prepackaged consistency policies, our framework splits consistency management into design choices along five orthogonal aspects, namely, concurrency control, replica synchronization, failure handling, update visibility and view isolation. Based on a detailed classification of application needs, the design choices can be combined to simultaneously enforce diverse consistency requirements for data access. We have designed and prototyped a middleware file store called Swarm that provides network-efficient wide area peer caching with configurable consistency. To demonstrate the practical effectiveness of the configurable consistency framework, we built four wide area network services that store data with distinct consistency needs in Swarm. Though existing middleware systems can individually support some of these services, none of them provides a consistency solution flexible enough to support all of the services efficiently. When these services employ caching with Swarm, they deliver more than 60% of the performance of custom-tuned implementations in terms of end-to-end latency, throughput and network economy. Also, Swarm-based wide-area peer caching improves service performance by 300 to 500% relative to client-server caching and RPCs.
Fault-based testing of Web Applications

As private consumers, businesses, and government agencies have come to rely on the Internet for important daily tasks, the demand for reliable, secure, and usable web-based applications has increased greatly. One major impediment to the production of reliable software is the labor and resource-intensive nature of software testing. A short time to market also deters developers from implementing appropriate test strategies. To increase reliability of such applications, automated, cost-effective test strategies that adequately test the continuously evolving web applications must be developed. Fault-based testing is a very effective technique for determining the validity of test suites. By introducing faults into code, either by hand-seeding or using an automated mutant generator, then running a set of tests on the mutants, one can determine if the test set is sufficient for the program. A set of algorithms for altering the code must be specified to seed faults. Two approaches to fault-based testing are hand-seeding and the use of mutation operators. Hand-seeding faults involves making a number of copies of each file of an application and injecting a single fault into each copy. Each faulty version of a file is then run against the test suite with the other, correct applications so that each fault is tested individually within otherwise clean code. By comparing the fault detection ability of test suites on hand-seeded faults and real faults found in widely-used programs, Andrews et al. have shown that hand-seeded faults are more difficult to detect than real faults [2]. Mutation tools have long been available for functional programs. The most widely used mutation system was Mothra [1], developed in 1987 to test Fortran programs and composed of a set of tools to perform individual tasks supporting mutant creation and testing. Chevalley and Thevenod-Fosse were the first to automate the use of mutation operators for object-oriented languages [7], but the tools were not publicly available and were unable to support the execution of mutants until the 2004 development of a mutation tool called MuJava [4]. Developed by Offutt, Ma, and Kwon, MuJava supports the generation and execution of both statement-level and object-oriented mutants in Java programs. No matter how much research is conducted on mutation testing some important questions remain:
The structure of Acinetobacter-secreted protease CpaA complexed with its chaperone CpaB reveals a novel mode of a T2SS chaperone–substrate interaction

Members of the Acinetobacter baumannii-calcoaceticus complex are nosocomial pathogens frequently causing multidrug-resistant infections that are increasing at alarming rates. A. baumannii has become the Gram-negative bacterium with the highest rate of multidrug resistance. As such, it is categorized by the World Health Organization as a critical priority for the research and development of new antimicrobial therapies. The zinc-dependent metalloendopeptidase CpaA is a predominant substrate of the type II secretion system (T2SS). CpaA is also a virulence factor of medically relevant Acinetobacter strains that specifically degrade the human glycoprotein coagulation factor XII and not its deglycosylated form, but the mechanism for this specificity is unknown. CpaB is a membrane-anchored T2SS chaperone that interacts with CpaA and is required for its stability and secretion. Here, we report the crystal structure of the CpaAB complex at 2.6-Å resolution, revealing four glycan-binding domains in CpaA that were not predicted from its primary sequence and may explain CpaA's glycoprotein-targeting activity. The structure of the complex identified a novel mode for chaperone–protease interactions in which the protease surrounds the chaperone. The CpaAB organization was akin to zymogen inactivation, with CpaB serving as a prodomain that inhibits catalytically active CpaA. CpaB contains a C-terminal tail that appears to block access to the CpaA catalytic site, and functional experiments with truncated variants indicated that this tail is dispensable for CpaA expression and secretion. Our results provide new insight into the mechanism of CpaA secretion and may inform the future development of therapeutic strategies for managing Acinetobacter infections.
Prediction of White Matter Hyperintensity in Brain MRI Using Fundus Photographs via Deep Learning

Purpose: We investigated whether a deep learning algorithm applied to retinal fundoscopic images could predict cerebral white matter hyperintensity (WMH), as represented by a modified Fazekas scale (FS), on brain magnetic resonance imaging (MRI). Methods: Participants who had undergone brain MRI and health-screening fundus photography at Hallym University Sacred Heart Hospital between 2010 and 2020 were consecutively included. The subjects were divided based on the presence of WMH, then classified into three groups according to the FS grade (0 vs. 1 vs. 2+) using age matching. Two pre-trained convolutional neural networks were fine-tuned and evaluated for prediction performance using 10-fold cross-validation. Results: A total of 3726 fundus photographs from 1892 subjects were included, of which 905 fundus photographs from 462 subjects were included in the age-matched balanced dataset. In predicting the presence of WMH, the mean area under the receiver operating characteristic curve was 0.736 ± 0.030 for DenseNet-201 and 0.724 ± 0.026 for EfficientNet-B7. For the prediction of FS grade, the mean accuracies reached 41.4 ± 5.7% with DenseNet-201 and 39.6 ± 5.6% with EfficientNet-B7. The deep learning models focused on the macula and retinal vasculature to detect an FS of 2+. Conclusions: Cerebral WMH might be partially predicted by non-invasive fundus photography via deep learning, which may suggest an eye–brain association.
Evaluate the ability of clinical decision support systems (CDSSs) to improve clinical practice.

INTRODUCTION Prevalence of new diseases, medical science promotion and increase of referring to health care centers, provide a good situation for medical errors growth. Errors can involve medicines, surgery, diagnosis, equipment, or lab reports. Medical errors can occur anywhere in the health care system: In hospitals, clinics, surgery centers, doctors' offices, nursing homes, pharmacies, and patients' homes. According to the Institute of Medicine (IOM), 98,000 people die every year from preventable medical errors. In 2010 from all referred medical error records to Iran Legal Medicine Organization, 46/5% physician and medical team members were known as delinquent. One of new technologies that can reduce medical errors is clinical decision support systems (CDSSs). METHODS This study was unsystematic-review study. The literature was searched on evaluate the "ability of clinical decision support systems to improve clinical practice" with the help of library, books, conference proceedings, data bank, and also searches engines available at Google, Google scholar. For our searches, we employed the following keywords and their combinations: medical error, clinical decision support systems, Computer-Based Clinical Decision Support Systems, information technology, information system, health care quality, computer systems in the searching areas of title, keywords, abstract, and full text. In this study, more than 100 articles and reports were collected and 38 of them were selected based on their relevancy. DISCUSSION AND CONCLUSION The CDSSs are computer programs, designed for help to health care careers. These systems as a knowledge-based tool could help health care manager in analyze evaluation, improvement and selection of effective solutions in clinical decisions. Therefore, it has a main role in medical errors reduction. The aim of this study was to express ability of the CDSSs to improve