Miracle-dz/UniFAR-FTUs huggingface dataset:
Lipid management in the proteinuric patient: do not overlook the importance of proteinuria reduction.

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An essential role for ATP binding and hydrolysis in the chaperone activity of GRP94 in cells

Glucose-regulated protein 94 (GRP94) is an endoplasmic reticulum (ER) chaperone for which only few client proteins and no cofactors are known and whose mode of action is unclear. To decipher the mode of GRP94 action in vivo, we exploited our finding that GRP94 is necessary for the production of insulin-like growth factor (IGF)-II and developed a cell-based functional assay. Grp94−/− cells are hypersensitive to serum withdrawal and die. This phenotype can be complemented either with exogenous IGF-II or by expression of functional GRP94. Fusion proteins of GRP94 with monomeric GFP (mGFP) or mCherry also rescue the viability of transiently transfected, GRP94-deficient cells, demonstrating that the fusion proteins are functional. Because these constructs enable direct visualization of chaperone-expressing cells, we used this survival assay to assess the activities of GRP94 mutants that are defective in specific biochemical functions in vitro. Mutations that abolish binding of adenosine nucleotides cannot support growth in serum-free medium. Similarly, mutations of residues needed for ATP hydrolysis also render GRP94 partially or completely nonfunctional. In contrast, an N-terminal domain mutant that cannot bind peptides still supports cell survival. Thus the peptide binding activity in vitro can be uncoupled from the chaperone activity toward IGF in vivo. This mutational analysis suggests that the ATPase activity of GRP94 is essential for chaperone activity in vivo and that the essential protein-binding domain of GRP94 is distinct from the N-terminal domain.
Sleep, School Performance, and a School-Based Intervention among School-Aged Children: A Sleep Series Study in China

Background Sufficient sleep during childhood is essential to ensure a transition into a healthy adulthood. However, chronic sleep loss continues to increase worldwide. In this context, it is imperative to make sleep a high-priority and take action to promote sleep health among children. The present series of studies aimed to shed light on sleep patterns, on the longitudinal association of sleep with school performance, and on practical intervention strategy for Chinese school-aged children. Methods and Findings A serial sleep researches, including a national cross-sectional survey, a prospective cohort study, and a school-based sleep intervention, were conducted in China from November 2005 through December 2009. The national cross-sectional survey was conducted in 8 cities and a random sample of 20,778 children aged 9.0±1.61 years participated in the survey. The five-year prospective cohort study included 612 children aged 6.8±0.31 years. The comparative cross-sectional study (baseline: n = 525, aged 10.80±0.41; post-intervention follow-up: n = 553, aged 10.81±0.33) was undertaken in 6 primary schools in Shanghai. A battery of parent and teacher reported questionnaires were used to collect information on children’s sleep behaviors, school performance, and sociodemographic characteristics. The mean sleep duration was 9.35±0.77 hours. The prevalence of daytime sleepiness was 64.4% (sometimes: 37.50%; frequently: 26.94%). Daytime sleepiness was significantly associated with impaired attention, learning motivation, and particularly, academic achievement. By contrast, short sleep duration only related to impaired academic achievement. After delaying school start time 30 minutes and 60 minutes, respectively, sleep duration correspondingly increased by 15.6 minutes and 22.8 minutes, respectively. Moreover, intervention significantly improved the sleep duration and daytime sleepiness. Conclusions Insufficient sleep and daytime sleepiness commonly existed and positively associated with the impairment of school performance, especially academic achievement, among Chinese school-aged children. The effectiveness of delaying school staring time emphasized the benefits of optimal school schedule regulation to children’s sleep health.
Interleukin-11 Promotes the Progress of Gastric Carcinoma via Abnormally Expressed Versican

Versican, a ubiquitous component of the extracellular matrix (ECM), accumulates both in tumor stroma and cancer cells and is highly regulated by various cytokines. The aberrant expression of versican and its isoforms is known to modulate cell proliferation, differentiation, and migration, all of which are features of the invasion and metastasis of cancer; versican is also known to favour the homeostasis of the ECM. Interleukin-11 (IL-11) is an important cytokine that exhibits a wide variety of biological effects in gastric cancer development. Here, we analysed the expression of versican isoforms and found that the major isoforms expressed by both gastric carcinoma tissue and gastric cell lines were V0 and V1, and V1 was significantly higher in gastric carcinoma tissue. The treatment of the gastric cell lines AGS and MKN45 with rhIL-11 resulted in a significant increase in the expression of V0 and V1. Exogenous IL-11 increased migration in AGS and MKN45 cells, whereas these effects were reversed when the expression of V0 and V1 were abolished by siRNA targeting versican V0/V1. Collectively, these findings suggest that the abnormally expressed versican and its isoforms participate, at least in part, in the progress of gastric carcinoma triggered by IL-11.
Structure of an invertebrate gene encoding cytoplasmic intermediate filament (IF) proteins: implications for the origin and the diversification of IF proteins.

The structure of the single gene encoding the cytoplasmic intermediate filament (IF) proteins in non‐neuronal cells of the gastropod Helix aspersa is described. Genomic and cDNA sequences show that the gene is composed of 10 introns and 11 exons, spanning greater than 60 kb of DNA. Alternative RNA processing accounts for two mRNA families which encode two IF proteins differing only in their C‐terminal sequence. The intron/exon organization of the Helix rod domain is identical to that of the vertebrate type III IF genes in spite of low overall protein sequence homology and the presence of an additional 42 residues in coil 1b of the invertebrate sequence. Intron position homology extends to the entire coding sequence comprising both the rod and tail domains when the invertebrate IF gene is compared with the nuclear lamin LIII gene of Xenopus laevis presented in the accompanying report of Döring and Stick. In contrast the intron patterns of the tail domains of the invertebrate IF and the lamin genes differ from those of the vertebrate type III genes. The combined data are in line with an evolutionary descent of cytoplasmic IF proteins from a nuclear lamin‐like progenitor and suggest a mechanism for this derivation. The unique position of intron 7 in the Helix IF gene indicates that the archetype IF gene arose by the elimination of the nuclear localization sequence due to the recruitment of a novel splice site. The presumptive structural organization of the archetype IF gene allows predictions with respect to the later diversification of metazoan IF genes. Whereas models proposing a direct derivation of neurofilament genes seem unlikely, the earlier speculation of an mRNA transposition mechanism is compatible with current results.
A Multiobjective Evolutionary Method for the Design of Peptidic Mimotopes

Peptides that mimic protein epitopes are interesting drug candidates. However, the design of effective peptidic drugs is difficult for several reasons, such as the fast degradation of peptides, their high flexibility, and thus high entropy loss on binding to the target. We therefore propose an in silico method for the automated design of peptides that are optimal with respect to several objectives. We present a Pareto-based multiobjective evolutionary algorithm for in silico peptide design. Using a simple molecular model, we apply the method to the design of peptides that (a) mimic antibody epitopes of the proteins thrombin and blood coagulation factor VIII, respectively, that (b) are short, and (c) are conformationally stable.
Physically aware High Level Synthesis design flow

High Level Synthesis (HLS) has many productivity advantages over traditional RTL design, but routing congestion is difficult to resolve due to the lack of physical information in HLS. In this paper we propose a novel design flow by integrating a HLS tool with physically aware logic synthesis technology. Using this approach, one can discover congestion problems early and trace their sources to specific parts of the input SystemC models. This allows designers to resolve the congestion problems before going to the layout design phase. We applied this flow to a large-scale HLS production design with results showing that this flow can significantly improve not only routing congestion but design area and timing as well.
Rethinking International Migration

A new style of international migration, temporary and often illegal immigration in order to work, began to emerge after World War II. Many countries initiated immigration policies that gave the appearance of control, while their back doors remained open and, possibly, unclosable. In the US, it is slowly becoming obvious that foreign workers cannot be used as a temporary labor force at will. 2 usual theories of migration are the classical and the conflicts schools. The classical school presents migration as a rational, economic act that leads to economic adjustment between sending and receiving countries. The conflict school, often Marxist, views migration as an unequal process that leads to the inclusion of developing countries into the world capitalist system and to a widenin gap between rich and poor countries. The convergence of these 2 theories leads to the idea that although migration may be a survival strategy of individuals and households, it is also determined by a country's integration in the world economic system. The author reviews several books on immigration theory, which appreciate the complexity and worldwide character of migration; indicate that migration patterns are persistent; and support the view that migration is an economic, social, and political problem; and recommend that policies must be integrated and address the entire issue.
Automatically Classifying Sentences in Full-Text Biomedical Articles into Introduction, Methods, Results and Discussion

Biomedical texts can be typically represented by four rhetorical categories: introduction, methods, results and discussion (IMRAD). Classifying sentences into these categories can benefit many other text-mining tasks. Although many studies have applied approaches to automatically classify sentences in MEDLINE abstracts into the IMRAD categories, few have explored the classification of sentences that appear in full-text biomedical articles. We explored different approaches to automatically classify a sentence in a full-text biomedical article into the IMRAD categories. Our best system is a support vector machine classifier that achieved 81.30% accuracy, which is significantly higher than baseline systems.
The origin of the Haitian cholera outbreak strain.

BACKGROUND Although cholera has been present in Latin America since 1991, it had not been epidemic in Haiti for at least 100 years. Recently, however, there has been a severe outbreak of cholera in Haiti. METHODS We used third-generation single-molecule real-time DNA sequencing to determine the genome sequences of 2 clinical Vibrio cholerae isolates from the current outbreak in Haiti, 1 strain that caused cholera in Latin America in 1991, and 2 strains isolated in South Asia in 2002 and 2008. Using primary sequence data, we compared the genomes of these 5 strains and a set of previously obtained partial genomic sequences of 23 diverse strains of V. cholerae to assess the likely origin of the cholera outbreak in Haiti. RESULTS Both single-nucleotide variations and the presence and structure of hypervariable chromosomal elements indicate that there is a close relationship between the Haitian isolates and variant V. cholerae El Tor O1 strains isolated in Bangladesh in 2002 and 2008. In contrast, analysis of genomic variation of the Haitian isolates reveals a more distant relationship with circulating South American isolates. CONCLUSIONS The Haitian epidemic is probably the result of the introduction, through human activity, of a V. cholerae strain from a distant geographic source. (Funded by the National Institute of Allergy and Infectious Diseases and the Howard Hughes Medical Institute.).
Lupus Susceptibility Genes on Human Chromosome 1

During the past five years, there has been an intense interest in studying candidate susceptibility genes for systemic lupus erythematosus (SLE). Many such studies have been focused on candidates located on chromosome 1, demonstrating association of certain genetic variants with SLE. Some of the tested candidate genes were chosen because they encode molecules with relevant immunological functions that may play a role in the pathogenesis of SLE. More recently, the identification of genomic segments linked to SLE has suggested novel positional candidate genes. Thus far, there is considerable evidence supporting that multiple genes on this chromosome contribute to the development and expression of SLE. This review highlights the genetic loci located on chromosome 1 that have recently been associated with SLE. These include loci encoding the tumor necrosis factor receptor 2 (TNFR2), complement component Clq, Fc7 receptors, T cell receptor ζ chain, interleukin-10 (IL-10), poly (ADP-ribose) polymerase (PARP), and HRES-1.
A computation using mutually exclusive processing is sufficient to identify specific Hedgehog signaling components

A system of more than one part can be deciphered by observing differences between the parts. A simple way to do this is by recording something absolute displaying a trait in one part and not in another: in other words, mutually exclusive computation. Conditional directed expression in vivo offers processing in more than one part of the system giving increased computation power for biological systems analysis. Here, I report the consideration of these aspects in the development of an in vivo screening assay that appears sufficient to identify components specific to a system.
Systematic investigation of the relationship between high myopia and polymorphisms of the MMP2, TIMP2, and TIMP3 genes by a DNA pooling approach.

PURPOSE This study examined the relationship between high myopia and three myopia candidate genes--matrix metalloproteinase 2 (MMP2) and tissue inhibitor of metalloproteinase-2 and -3 (TIMP2 and TIMP3)--involved in scleral remodeling. METHODS Recruited for the study were unrelated adult Han Chinese who were high myopes (spherical equivalent, ≤ -6.0 D in both eyes; cases) and emmetropes (within ±1.0 D in both eyes; controls). Sample set 1 had 300 cases and 300 controls, and sample set 2 had 356 cases and 354 controls. Forty-nine tag single-nucleotide polymorphisms (SNPs) were selected from these candidate genes. The first stage was an initial screen of six case pools and six control pools constructed from sample set 1, each pool consisting of 50 distinct subjects of the same affection status. In the second stage, positive SNPs from the first stage were confirmed by genotyping individual samples forming the DNA pools. In the third stage, positive SNPs from stage 2 were replicated, with sample set 2 genotyped individually. RESULTS Of the 49 SNPs screened by DNA pooling, three passed the lenient threshold of P < 0.10 (nested ANOVA) and were followed up by individual genotyping. Of the three SNPs genotyped, two TIMP3 SNPs were found to be significantly associated with high myopia by single-marker or haplotype analysis. However, the initial positive results could not be replicated by sample set 2. CONCLUSIONS MMP2, TIPM2, and TIMP3 genes were not associated with high myopia in this Chinese sample and hence are unlikely to play a major role in the genetic susceptibility to high myopia.
Ubiquitin-Like Protein Involved in the Proteasome Pathway of Mycobacterium tuberculosis

The protein modifier ubiquitin is a signal for proteasome-mediated degradation in eukaryotes. Proteasome-bearing prokaryotes have been thought to degrade proteins via a ubiquitin-independent pathway. We have identified a prokaryotic ubiquitin-like protein, Pup (Rv2111c), which was specifically conjugated to proteasome substrates in the pathogen Mycobacterium tuberculosis. Pupylation occurred on lysines and required proteasome accessory factor A (PafA). In a pafA mutant, pupylated proteins were absent and substrates accumulated, thereby connecting pupylation with degradation. Although analogous to ubiquitylation, pupylation appears to proceed by a different chemistry. Thus, like eukaryotes, bacteria may use a small-protein modifier to control protein stability.
Pure Oats as Part of the Canadian Gluten-Free Diet in Celiac Disease: The Need to Revisit the Issue

The question about recommending pure, noncontaminated oats as part of the gluten-free diet of patients with celiac disease remains controversial. This might be due to gluten cross contamination and to the possible immunogenicity of some oat cultivars. In view of this controversy, a review of the scientific literature was conducted to highlight the latest findings published between 2008 and 2014 to examine the current knowledge on oats safety and celiac disease in Europe and North America. Results showed that regular oats consumed in Canada are largely contaminated. Overall, the consumption of pure oats has been generally considered to be safe for adults and children. However, it appears that some oat cultivars may trigger an immune response in sensitive individuals. Therefore, further long-term studies on the impact of consumption of oats identifying the cultivar(s) constitute an important step forward for drawing final recommendations. Furthermore, a closer and more accurate monitoring of the dietary intake of noncontaminated oats would be paramount to better determine what its actual contribution in the gluten-free diet of adults and children with celiac disease are in order to draw sound recommendations on the safety of pure oats as part of the gluten-free diet.
Localisation Basée Vision : de l'hétérogénéité des approches et des données

De nos jours, nous disposons d'une grande diversite de donnees sur les lieux qui nous entourent. Ces donnees peuvent etre de natures tres differentes : une collection d'images, un modele 3D, un nuage de points colorises, etc. Lorsque les GPS font defaut, ces informations peuvent etre tres utiles pour localiser un agent dans son environnement s'il peut lui-meme acquerir des informations a partir d'un systeme de vision. On parle alors de Localisation Basee Vision (LBV). De par la grande heterogeneite des donnees acquises et connues sur l'environnement, il existe de nombreux travaux traitant de ce probleme. Cet article a pour objet de passer en revue les differentes methodes recentes pour localiser un systeme de vision a partir d'une connaissance a priori sur l'environnement dans lequel il se trouve.
Definability and decidability of binary predicates for time granularity

In this paper, we study the definability and decidability of binary predicates for time granularity with respect to monadic theories over finitely and infinitely layered structures. We focus our attention on the equi-level (resp. equi-column) predicate constraining two time points to belong to the same layer (resp. column) and on the horizontal (resp. vertical) successor predicate relating a time point to its successor within a given layer (resp. column). We give a number of positive and negative results by reduction to/from a wide spectrum of decidable/undecidable problems.
THE INTRACELLULAR GROWTH OF BACTERIOPHAGES

A method is described for liberating and estimating intracellular bacteriophage at any stage during the latent period by arresting phage growth and inducing premature lysis of the infected cells. This is brought about by placing the infected bacteria into the growth medium supplemented with 0.01 M cyanide and with a high titer T6 lysate. It was found in some of the later experiments that the T6 lysate is essential only during the first half of the latent period. Cyanide alone will induce lysis during the latter part of the latent period. Using this method on T4-infected bacteria it is found that during the first half of the latent period no phage particles, not even those originally infecting the bacteria, are recovered. This result is in agreement with the gradually emerging concept that a profound alteration of the infecting phage particle takes place before reproduction ensues. During the second half of the latent period mature phage is found to accumulate within the bacteria at a rate which is parallel to the approximately linear increase of intracellular DNA in this system. However, the phage production lags several minutes behind DNA production. When 5-methyltryptophan replaced cyanide as the metabolic inhibitor, similar results were obtained. The curves were, however, displaced several minutes to the left on the time axis. The results are compared with Latarjet's (16) data on x-radiation of infected bacteria and with Foster's data (18) concerning the effect of proflavine on infected bacteria. Essential agreement with both is apparent.