Miracle-dz/UniFAR-FTUs huggingface dataset:
Dysfunction of Myosin Light‐Chain 4 (MYL4) Leads to Heritable Atrial Cardiomyopathy With Electrical, Contractile, and Structural Components: Evidence From Genetically‐Engineered Rats

Background There is increasing interest in the concept of atrial cardiomyopathy, but the underlying molecular and mechanistic determinants remain poorly defined. We identified a family with heritable atrial cardiomyopathy manifesting as progressive atrial‐selective electromechanical dysfunction, tachyarrhythmias, and bradyarrhythmias requiring pacemaker implantation. Myosin light‐chain 4 (MYL4), encoding the atrial‐selective essential myosin light chain, was identified as a candidate gene. We used genetically modified rat models to investigate the role of MYL4 in atrial cardiomyopathy. Methods and Results Exome sequencing and systematic bioinformatic analyses identified a rare missense variant of MYL4 (c.31G>A [p.E11K]) in a large multiplex atrial cardiomyopathy family pedigree. The mutation cosegregated with atrial standstill (selected as the principal presenting trait) with a logarithm of the odds score of 5.3. The phenotype of rats with MYL4 mutation knock‐in confirmed the causative role of the mutation. MYL4 knockout rats showed a similar atrial cardiomyopathy phenotype, whereas rats with an adjacent 4‐amino‐acid deletion showed no phenotype. Both MYL4 p.E11K knock‐in rats and MYL4 knockout rats showed progressive atrial electrophysiological, contractile, and fibrotic abnormalities, similar to affected patients. Biochemical analyses of MYL4 p.E11K mutation rats showed activation of proapoptotic and profibrotic signaling, along with increased atrial‐cardiomyocyte terminal deoxynucleotidyl transferase dUTP nick end labeling staining, suggesting enhanced apoptotic cell death, findings that were mimicked by in vitro adenoviral transfer of the mutant gene to neonatal‐rat cardiomyocytes. Conclusions Loss‐of‐function MYL4 gene variants cause progressive atrial cardiomyopathy in humans and rats. Our findings identify MYL4 as a key gene required for atrial contractile, electrical and structural integrity. These results improve our understanding of the molecular basis of atrial cardiomyopathy and introduce new models for further mechanistic analysis.
A Formal Approach for Securing XML Document

With the ever increasing demand for the Web-based applications over the Internet, the related security issue has become a great concern. Web document security has been studied by many researchers and various security mechanisms have been proposed. The aim of this article is to investigate the security issue of the XML documents. We discuss a protection mechanism and investigate a formal approach to ensure the security of Web-based XML documents. Our approach starts by introducing a high level language to specify an XML document and its protection authorizations. We also discuss and investigate the syntax and semantics of the language. The flexible and powerful access control specification can effectively protect the documents from unauthorized attempts.
Genetic polymorphisms of the apolipoprotein A‐IV in a Greek population and their relation to plasma lipid and lipoprotein levels

Apolipoprotein (apo) A‐IV is a protein component of triglyceride‐rich lipoproteins and high‐density lipoproteins (HDL). In this study, two common genetic polymorphisms of the apoA‐IV gene [codons 347(allele A and T) and 360 (allele 1 and 2)] were investigated in Greek patients with hyperlipidaemia and in healthy individuals matched for age, sex and smoking habits. In both study populations we evaluated the effect of these polymorphic sites on lipid and lipoprotein plasma levels and the body mass index (BMI). The frequencies of the 1/1 and 1/2 genotypes in codon 360 were 0.94 and 0.06 in hyperlipidemic patients and 0.92 and 0.08 in the control population, respectively. The frequencies of the A/A, A/T and T/T genotypes in codon 347 were 0.62, 0.34 and 0.04 in hyperlipidemic patients and 0.59, 0.33 and 0.08 in the control population, respectively. None of the above genotype frequency differences between the study populations reached statistical significance. The control population was not affected by any polymorphism of the apo A‐IV gene. Hyperlipidaemic patients, carriers of the allele 2 (1/2 genotype), had significantly lower plasma triglyceride levels than carriers of the allele 1 (p = 0.03). Genetic variation in codon 347 had no influence on lipid and lipoprotein plasma levels. None of the polymorphisms at codons 360 and 347 affected the BMI. In conclusion, this study describes for the first time the genotype frequencies for polymorphic sites in codons 360 and 347 of the apo A‐IV gene in a Greek population and suggests that the presence of the allele 2 is associated with lower plasma triglyceride levels in hyperlipidaemic patients.
Crocodiles in the Sahara Desert: An Update of Distribution, Habitats and Population Status for Conservation Planning in Mauritania

Background Relict populations of Crocodylus niloticus persist in Chad, Egypt and Mauritania. Although crocodiles were widespread throughout the Sahara until the early 20th century, increased aridity combined with human persecution led to local extinction. Knowledge on distribution, occupied habitats, population size and prey availability is scarce in most populations. This study evaluates the status of Saharan crocodiles and provides new data for Mauritania to assist conservation planning. Methodology/Principal Findings A series of surveys in Mauritania detected crocodile presence in 78 localities dispersed across 10 river basins and most tended to be isolated within river basins. Permanent gueltas and seasonal tâmoûrts were the most common occupied habitats. Crocodile encounters ranged from one to more than 20 individuals, but in most localities less than five crocodiles were observed. Larger numbers were observed after the rainy season and during night sampling. Crocodiles were found dead in between water points along dry river-beds suggesting the occurrence of dispersal. Conclusion/Significance Research priorities in Chad and Egypt should focus on quantifying population size and pressures exerted on habitats. The present study increased in by 35% the number of known crocodile localities in Mauritania. Gueltas are crucial for the persistence of mountain populations. Oscillations in water availability throughout the year and the small dimensions of gueltas affect biological traits, including activity and body size. Studies are needed to understand adaptation traits of desert populations. Molecular analyses are needed to quantify genetic variability, population sub-structuring and effective population size, and detect the occurrence of gene flow. Monitoring is needed to detect demographical and genetical trends in completely isolated populations. Crocodiles are apparently vulnerable during dispersal events. Awareness campaigns focusing on the vulnerability and relict value of crocodiles should be implemented. Classification of Mauritanian mountains as protected areas should be prioritised.
Substrate Specificities of MexAB-OprM, MexCD-OprJ, and MexXY-OprM Efflux Pumps in Pseudomonas aeruginosa

ABSTRACT To find the exact substrate specificities of three species of tripartite efflux systems of Pseudomonas aeruginosa, MexAB-OprM, MexCD-OprJ, and MexXY-OprM, we constructed a series of isogenic mutants, each of which constitutively overproduced one of the three efflux systems and lacked the other two, and their isogenic mutants, which lacked all these systems. Comparison of the susceptibilities of the constructed mutants to 52 antimicrobial agents belonging to various groups suggested the following substrate specificities. All of the efflux systems extrude a wide variety of antimicrobial agent groups, i.e., quinolones, macrolides, tetracyclines, lincomycin, chloramphenicol, most penicillins (all but carbenicillin and sulbenicillin), most cephems (all but cefsulodin and ceftazidime), meropenem, and S-4661, but none of them extrude polymyxin B or imipenem. Extrusion of aminoglycosides is specific to MexXY-OprM, and extrusion of a group of the β-lactams, i.e., carbenicillin, sulbenicillin, ceftazidime, moxalactam, and aztreonam, is specific to MexAB-OprM. Moreover, MexAB-OprM and MexCD-OprJ extrude novobiocin, cefsulodin, and flomoxef, while MexXY-OprM does not. These substrate specificities are distinct from those reported previously.
Cross-Modal Plasticity and Speech Perception in Pre- and Postlingually Deaf Cochlear Implant Users

Objective: A great amount of variability is observed in speech perception outcomes with cochlear implants. The mechanisms behind the observed variability need to be elucidated. One possible mechanism contributing to the observed variability is the development of cross-modal plasticity. This study examines the association between visual/auditory cross-modal plasticity and speech perception with a cochlear implant in individuals with pre- and postlingual onset of severe to profound hearing loss. Design: The N1 visual evoked potential (VEP) in response to peripheral visual motion stimuli was recorded in individuals with pre- (N = 10) and postlingual (N = 12) onset of severe to profound hearing loss who use a cochlear implant. The association between the amplitude of the N1 VEP response over the right temporal lobe and sentence and word perception scores obtained with the cochlear implant was examined through linear regression analyses. In addition, the association between the duration of auditory deprivation and the amplitude of the N1 VEP response was examined. Results: As the amplitude of the N1 VEP recorded over the right temporal lobe increased, speech perception scores in individuals with prelingual onset of severe to profound hearing loss decreased. However, a clear association between the amplitude of the N1 VEP over the right temporal lobe and speech perception scores was not observed for individuals with postlingual onset of severe to profound hearing loss. Neither group demonstrated an association between the amplitude of the VEP over the right temporal lobe and the duration of auditory deprivation before cochlear implantation. Conclusion: The results suggest that cross-modal plasticity accounts for a significant amount of the variability observed in speech perception performance with a cochlear implant in individuals with prelingual onset of severe to profound hearing loss but not in individuals who acquire severe to profound hearing loss later in life. Furthermore, the results suggest that the influence of cross-modal plasticity on speech perception ability is more greatly influenced by when (pre- or postlingually) a person acquires a severe to profound hearing impairment rather than the duration of auditory deprivation before receipt of a cochlear implant.
Rewriting Regular XPath Queries on XML Views

We study the problem of answering queries posed on virtual views of XML documents, a problem commonly encountered when enforcing XML access control and integrating data. We approach the problem by rewriting queries on views into equivalent queries on the underlying document, and thus avoid the overhead of view materialization and maintenance. We consider possibly recursively defined XML views and study the rewriting of both XPath and regular XPath queries. We show that while rewriting is not always possible for XPath over recursive views, it is for regular XPath; however, the rewritten query may be of exponential size. To avoid this prohibitive cost we propose a rewriting algorithm that characterizes rewritten queries as a new form of automata, and an efficient algorithm to evaluate the automaton-represented queries. These allow us to answer queries on views in linear time. We have fully implemented a prototype system, SMOQE, which yields the first regular XPath engine and a practical solution for answering queries over possibly recursively defined XML views.
Pruning in ordered bagging ensembles

We present a novel ensemble pruning method based on reordering the classifiers obtained from bagging and then selecting a subset for aggregation. Ordering the classifiers generated in bagging makes it possible to build subensembles of increasing size by including first those classifiers that are expected to perform best when aggregated. Ensemble pruning is achieved by halting the aggregation process before all the classifiers generated are included into the ensemble. Pruned subensembles containing between 15% and 30% of the initial pool of classifiers, besides being smaller, improve the generalization performance of the full bagging ensemble in the classification problems investigated.
Global analysis for functional residues of histone variant Htz1 using the comprehensive point mutant library

Histone variants perform unique functions and are deposited onto DNA by mechanisms distinct from those of canonical histones. The H2A variant, H2A.Z, also known as Htz1 in Saccharomyces cerevisiae, is not uniformly distributed across the genome but facilitates transcriptional activation at target gene promoters and anti‐silencing at heterochromatin loci. Htz1 is also involved in DNA replication, DNA repair, chromosome segregation and cell cycle control. Its sequence identity to canonical H2A is only ∼60%, and it is likely that the nonconserved residues are responsible for Htz1‐specific functions. However, precise roles of these variant‐specific residues are not well understood. To gain insights into the molecular basis underlying the functional differences between canonical and variant histones, 117 alanine‐scanning point mutants of Htz1 were constructed for this study, and chemical genetic screens were carried out. Consequently, seven Htz1 residues that conferred one or more abnormal phenotypes when mutated were identified. Based on primary sequence and functional conservation between H2A and Htz1, two of these residues (F32 and I109) appear to have an Htz1‐specific role, whereas the rest seem to have functions shared between H2A and Htz1. This study provides a useful resource for future investigations into functional convergence and divergence between canonical and variant histones.
Protecting Poorly Chosen Secrets from Guessing Attacks

In a security system that allows people to choose their own passwords, people tend to choose passwords that can be easily guessed. This weakness exists in practically all widely used systems. Instead of forcing users to choose secrets that are likely to be difficult for them to remember, solutions that maintain user convenience and a high level of security at the same time are proposed. The basic idea is to ensure that data available to the attacker is sufficiently unpredictable to prevent an offline verification of whether a guess is successful or not. Common forms of guessing attacks are examined, examples of cryptographic protocols that are immune to such attacks are developed, and a systematic way to examine protocols to detect vulnerabilities to such attacks is suggested. >
Synaptic and Vesicular Coexistence of VGLUT and VGAT in Selected Excitatory and Inhibitory Synapses

The segregation between vesicular glutamate and GABA storage and release forms the molecular foundation between excitatory and inhibitory neurons and guarantees the precise function of neuronal networks. Using immunoisolation of synaptic vesicles, we now show that VGLUT2 and VGAT, and also VGLUT1 and VGLUT2, coexist in a sizeable pool of vesicles. VGAT immunoisolates transport glutamate in addition to GABA. Furthermore, VGLUT activity enhances uptake of GABA and monoamines. Postembedding immunogold double labeling revealed that VGLUT1, VGLUT2, and VGAT coexist in mossy fiber terminals of the hippocampal CA3 area. Similarly, cerebellar mossy fiber terminals harbor VGLUT1, VGLUT2, and VGAT, while parallel and climbing fiber terminals exclusively contain VGLUT1 or VGLUT2, respectively. VGLUT2 was also observed in cerebellar GABAergic basket cells terminals. We conclude that the synaptic coexistence of vesicular glutamate and GABA transporters allows for corelease of both glutamate and GABA from selected nerve terminals, which may prevent systemic overexcitability by downregulating synaptic activity. Furthermore, our data suggest that VGLUT enhances transmitter storage in nonglutamatergic neurons. Thus, synaptic and vesicular coexistence of VGLUT and VGAT is more widespread than previously anticipated, putatively influencing fine-tuning and control of synaptic plasticity.
Obstacles are beneficial to me! Scaffold-based locomotion of a snake-like robot using decentralized control

Snakes are able to move effectively by using terrain irregularities as scaffolds against which they push their bodies. This locomotion is attractive from a robotic viewpoint because irregularities in the environment of conventional robots interfere with their operation. In a previous work, we proposed a decentralized control mechanism of the scaffold-based locomotion of snakes, which combined curvature derivative control with local pressure reflex. Here, we practically demonstrate how a snake-like robot utilizing the proposed control scheme moves effectively by pushing its body against pegs.
Integrated simultaneous analysis of different biomedical data types with exact weighted bi-cluster editing

The explosion of biological data has largely influenced the focus of today’s biology research. Integrating and analysing large quantity of data to provide meaningful insights has become the main challenge to biologists and bioinformaticians. One major problem is the combined data analysis of data from different types, such as phenotypes and genotypes. This data is modelled as bi-partite graphs where nodes correspond to the different data points, mutations and diseases for instance, and weighted edges relate to associations between them. Bi-clustering is a special case of clustering designed for partitioning two different types of data simultaneously. We present a bi-clustering approach that solves the NP-hard weighted bi-cluster editing problem by transforming a given bi-partite graph into a disjoint union of bi-cliques. Here we contribute with an exact algorithm that is based on fixed-parameter tractability. We evaluated its performance on artificial graphs first. Afterwards we exemplarily applied our Java implementation to data of genome-wide association studies (GWAS) data aiming for discovering new, previously unobserved geno-to-pheno associations. We believe that our results will serve as guidelines for further wet lab investigations. Generally our software can be applied to any kind of data that can be modelled as bi-partite graphs. To our knowledge it is the fastest exact method for weighted bi-cluster editing problem.
Autophagy in Innate Recognition of Pathogens and Adaptive Immunity

Autophagy is a specialized cellular pathway involved in maintaining homeostasis by degrading long-lived cellular proteins and organelles. Recent studies have demonstrated that autophagy is utilized by immune systems to protect host cells from invading pathogens and regulate uncontrolled immune responses. During pathogen recognition, induction of autophagy by pattern recognition receptors leads to the promotion or inhibition of consequent signaling pathways. Furthermore, autophagy plays a role in the delivery of pathogen signatures in order to promote the recognition thereof by pattern recognition receptors. In addition to innate recognition, autophagy has been shown to facilitate MHC class II presentation of intracellular antigens to activate CD4 T cells. In this review, we describe the roles of autophagy in innate recognition of pathogens and adaptive immunity, such as antigen presentation, as well as the clinical relevance of autophagy in the treatment of human diseases.
Improving Cloud Optical Property Retrievals for Partly Cloudy Pixels Using Coincident Higher‐Resolution Single Band Measurements: A Feasibility Study Using ASTER Observations

Clear‐sky contamination is a challenging and long‐lasting problem for cloud optical thickness (τ) and effective droplet radius (reff) retrievals using passive satellite sensors. This study explores the feasibility of improving both τ and reff retrievals for partly cloudy (PCL) pixels by using available subpixel samples in a visible to near‐infrared band, which many satellite sensors offer. Data are provided by high‐resolution reflectance (R) observations and cloud property retrievals by the Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) at horizontal resolutions between 30‐960m. For partly cloudy 960‐m observations, the clear‐sky component of the pixels induces significant underestimations of up to 58% for τ, while overestimations in reff can exceed 41%. This yields underestimations in the derived liquid water path and cloud droplet number concentration of up to 68% and 72%, respectively. By means of three different assumptions it is shown that subpixel R observations in the visible to near‐infrared band can be used to estimate higher‐resolution R for the second band in the retrieval scheme, as well as the subpixel cloud cover. The estimated values compare well to actually observed ASTER results and are used to retrieve cloud properties, which are unbiased by the clear‐sky component of PCL pixels. While the presented retrieval approach is only evaluated for marine boundary layer clouds, it is computationally efficient and can be easily applied to observations from different imagers. As an example, the PCL retrieval scheme is applied to data by the Moderate Resolution Imaging Spectroradiometer, where similar biases for PCL pixels are observed.
Efficient object retrieval from videos

We describe an approach to video object retrieval which enables all shots containing the object to be returned in a manner, and with a speed, similar to a Google search for text. The object is specified by a user outlining it in an image, and the object is then delineated in the retrieved shots. The method is based on three components: (i) an image representation of the object by a set of viewpoint invariant region descriptors so that recognition can proceed successfully despite changes in viewpoint, illumination and partial occlusion; (ii) the use of contiguous frames within a shot in order to improve the estimation of the descriptors and motion group object visual aspects; (iii) vector quantization of the descriptors so that the technology of text retrieval, such as inverted file systems, can be employed at run time. The method is illustrated on a full length feature film.
Phylogeny-based species delimitation of southern Philippines bent-toed geckos and a new species of Cyrtodactylus (Squamata: Gekkonidae) from western Mindanao and the Sulu Archipelago

Using a combination of fixed morphological character differences, mitochondrial DNA sequence data, and an estimate of phylogeny as our guide, we describe a new species of bent-toed gekkonid lizard (Genus: Cyrtodactylus) from southwestern Mindanao Island, and northeastern portions of the Sulu Archipelago, southern Philippines. The new species resembles C. annulatus, but differs from this and all other congeners by characteristics of external morphology, color pattern, and body size. In addition, the new species is distinguished from congeners by marked genetic divergence and reciprocal monophyly of mitochondrial DNA sequences. The new species is common in pristine, low elevation gallery forests throughout Pasonanca Natural Park, Zamboanga Peninsula, southwestern Mindanao Island, and the northeastern portions of the Sulu Archipelago.