Miracle-dz/UniFAR-FTUs huggingface dataset:
Allosteric Effects of Permeating Cations on Gating Currents during K+ Channel Deactivation

K+ channel gating currents are usually measured in the absence of permeating ions, when a common feature of channel closing is a rising phase of off-gating current and slow subsequent decay. Current models of gating invoke a concerted rearrangement of subunits just before the open state to explain this very slow charge return from opening potentials. We have measured gating currents from the voltage-gated K+ channel, Kv1.5, highly overexpressed in human embryonic kidney cells. In the presence of permeating K+ or Cs+, we show, by comparison with data obtained in the absence of permeant ions, that there is a rapid return of charge after depolarizations. Measurement of off-gating currents on repolarization before and after K+ dialysis from cells allowed a comparison of off-gating current amplitudes and time course in the same cells. Parallel experiments utilizing the low permeability of Cs+ through Kv1.5 revealed similar rapid charge return during measurements of off-gating currents at ECs. Such effects could not be reproduced in a nonconducting mutant (W472F) of Kv1.5, in which, by definition, ion permeation was macroscopically absent. This preservation of a fast kinetic structure of off-gating currents on return from potentials at which channels open suggests an allosteric modulation by permeant cations. This may arise from a direct action on a slow step late in the activation pathway, or via a retardation in the rate of C-type inactivation. The activation energy barrier for K+ channel closing is reduced, which may be important during repetitive action potential spiking where ion channels characteristically undergo continuous cyclical activation and deactivation.
Strip force and strength evolution of optical fibers with opened coating

The Strip Force test is widely used in the fiber optic telecommunications industry. This force is connected with the mechanical properties of the coatings, and in some extent with the adhesion between the coating and the glass. If the polymer coating fails by cracks or delamination with water penetration, it can cause fiber strength degradation, because of the glass humidity susceptibility. Until now there has been no correlation found between strength degradation, strip force and coating damages. In this study the strip force and the strength were measured for different fibers aged in harsh environment for long periods of time. Short and long samples were used. Short samples are like coating damaged fibers opened to the humid environment, and the long samples simulated long length of fibers inside cable structures. The results of the tests point out the everlasting life of the strip force and coating quality, opposing to the strength degradation of fibers under long term aging.
Visualizing Epithelial Expression in Vertical and Horizontal Planes With Dual Axes Confocal Endomicroscope Using Compact Distal Scanner

The epithelium is a thin layer of tissue that lines hollow organs, such as colon. Visualizing in vertical cross sections with sub-cellular resolution is essential to understanding early disease mechanisms that progress naturally in the plane perpendicular to the tissue surface. The dual axes confocal architecture collects optical sections in tissue by directing light at an angle incident to the surface using separate illumination and collection beams to reduce effects of scattering, enhance dynamic range, and increase imaging depth. This configuration allows for images to be collected in the vertical as well as horizontal planes. We designed a fast, compact monolithic scanner based on the principle of parametric resonance. The mirrors were fabricated using microelectromechanical systems (MEMS) technology and were coated with aluminum to maximize near-infrared reflectivity. We achieved large axial displacements <inline-formula> <tex-math notation="LaTeX">$> 400~\mu \text{m}$ </tex-math></inline-formula> and wide lateral deflections >20°. The MEMS chip has a <inline-formula> <tex-math notation="LaTeX">$3.2\times2.9$ </tex-math></inline-formula> mm<sup>2</sup> form factor that allows for efficient packaging in the distal end of an endomicroscope. Imaging can be performed in either the vertical or horizontal planes with <inline-formula> <tex-math notation="LaTeX">$430~\mu \text{m}$ </tex-math></inline-formula> depth or <inline-formula> <tex-math notation="LaTeX">$1 \times 1$ </tex-math></inline-formula> mm<sup>2</sup> area, respectively, at 5 frames/s. We systemically administered a Cy5.5-labeled peptide that is specific for EGFR, and collected near-infrared fluorescence images ex vivo from pre-malignant mouse colonic epithelium to reveal the spatial distribution of this molecular target. Here, we demonstrate a novel scanning mechanism in a dual axes confocal endomicroscope that collects optical sections of near-infrared fluorescence in either vertical or horizontal planes to visualize molecular expression in the epithelium.
Progressive meshes

Highly detailed geometric models are rapidly becoming commonplace in computer graphics. These models, often represented as complex triangle meshes, challenge rendering performance, transmission bandwidth, and storage capacities. This paper introduces the progressive mesh (PM) representation, a new scheme for storing and transmitting arbitrary triangle meshes. This efficient, lossless, continuous-resolution representation addresses several practical problems in graphics: smooth geomorphing of level-of-detail approximations, progressive transmission, mesh compression, and selective refinement. In addition, we present a new mesh simplification procedure for constructing a PM representation from an arbitrary mesh. The goal of this optimization procedure is to preserve not just the geometry of the original mesh, but more importantly its overall appearance as defined by its discrete and scalar appearance attributes such as material identifiers, color values, normals, and texture coordinates. We demonstrate construction of the PM representation and its applications using several practical models.
Climate Warming, Marine Protected Areas and the Ocean-Scale Integrity of Coral Reef Ecosystems

Coral reefs have emerged as one of the ecosystems most vulnerable to climate variation and change. While the contribution of a warming climate to the loss of live coral cover has been well documented across large spatial and temporal scales, the associated effects on fish have not. Here, we respond to recent and repeated calls to assess the importance of local management in conserving coral reefs in the context of global climate change. Such information is important, as coral reef fish assemblages are the most species dense vertebrate communities on earth, contributing critical ecosystem functions and providing crucial ecosystem services to human societies in tropical countries. Our assessment of the impacts of the 1998 mass bleaching event on coral cover, reef structural complexity, and reef associated fishes spans 7 countries, 66 sites and 26 degrees of latitude in the Indian Ocean. Using Bayesian meta-analysis we show that changes in the size structure, diversity and trophic composition of the reef fish community have followed coral declines. Although the ocean scale integrity of these coral reef ecosystems has been lost, it is positive to see the effects are spatially variable at multiple scales, with impacts and vulnerability affected by geography but not management regime. Existing no-take marine protected areas still support high biomass of fish, however they had no positive affect on the ecosystem response to large-scale disturbance. This suggests a need for future conservation and management efforts to identify and protect regional refugia, which should be integrated into existing management frameworks and combined with policies to improve system-wide resilience to climate variation and change.
Effect of hypo‐ and hyperthyroidism on the function and metabolism of macrophages in rats

The effect of thyroid hormones on monocyte migration, phagocytic capacity and hydrogen peroxide production by macrophages and the effect of these hormones on glutamine and glucose metabolism was investigated. The experiments were performed on resident, thioglycollate‐ and BCG‐stimulated cells from hypo‐ and hyperthyroid rats. High plasma levels of thyroid hormones suppressed the migration of monocytes and hydrogen peroxide production, whereas hypothyuroidism did not affect cell migration but rasied the phagocytic capacity and the hydrogen peroxide production. Hyperthyroidism increased the activities of glutaminase and hexokinase and the rates of decarboxylation of [U‐14C]‐glutamine and [U‐14C]‐glucose in inflammatory and activated cells. Hypothyroidism stimulated glucose metabolism and had only a slight effect on glutaminolysis. The activity of the TCA cycle was, however, diminished in the presence of high plasma levels of thyroid hormones and enhanced by the hypothyroid state. These findings suggest that the functional changes observed are more likely to be related to the activity of the TCA cycle rather than to glutaminolysis and glycolysis.
A novel string-to-string distance measure with applications to machine translation evaluation

We introduce a string-to-string distance measure which extends the edit distance by block transpositions as constant cost edit operation. An algorithm for the calculation of this distance measure in polynomial time is presented. We then demonstrate how this distance measure can be used as an evaluation criterion in machine translation. The correlation between this evaluation criterion and human judgment is systematically compared with that of other automatic evaluation measures on two translation tasks. In general, like other automatic evaluation measures, the criterion shows low correlation at sentence level, but good correlation at system level.
miR-34a Modulates Angiotensin II-Induced Myocardial Hypertrophy by Direct Inhibition of ATG9A Expression and Autophagic Activity

Cardiac hypertrophy is characterized by thickening myocardium and decreasing in heart chamber volume in response to mechanical or pathological stress, but the underlying molecular mechanisms remain to be defined. This study investigated altered miRNA expression and autophagic activity in pathogenesis of cardiac hypertrophy. A rat model of myocardial hypertrophy was used and confirmed by heart morphology, induction of cardiomyocyte autophagy, altered expression of autophagy-related ATG9A, LC3 II/I and p62 proteins, and decrease in miR-34a expression. The in vitro data showed that in hypertrophic cardiomyocytes induced by Ang II, miR-34a expression was downregulated, whereas ATG9A expression was up-regulated. Moreover, miR-34a was able to bind to ATG9A 3′-UTR, but not to the mutated 3′-UTR and inhibited ATG9A protein expression and autophagic activity. The latter was evaluated by autophagy-related LC3 II/I and p62 levels, TEM, and flow cytometry in rat cardiomyocytes. In addition, ATG9A expression induced either by treatment of rat cardiomyocytes with Ang II or ATG9A cDNA transfection upregulated autophagic activity and cardiomyocyte hypertrophy in both morphology and expression of hypertrophy-related genes (i.e., ANP and β-MHC), whereas knockdown of ATG9A expression downregulated autophagic activity and cardiomyocyte hypertrophy. However, miR-34a antagonized Ang II-stimulated myocardial hypertrophy, whereas inhibition of miR-34a expression aggravated Ang II-stimulated myocardial hypertrophy (such as cardiomyocyte hypertrophy-related ANP and β-MHC expression and cardiomyocyte morphology). This study indicates that miR-34a plays a role in regulation of Ang II-induced cardiomyocyte hypertrophy by inhibition of ATG9A expression and autophagic activity.
Kawasaki syndrome hospitalizations in Ireland, 1996 through 2000

Objective. To describe the epidemiologic characteristics and estimate the incidence of Kawasaki syndrome (KS) among children in Ireland. Methods. Hospital discharge records with a KS diagnosis among patients <18 years of age were examined using Ireland’s Hospital In-Patient Enquiry database for 1996 through 2000. Results. During the study period 265 hospitalizations associated with KS among children <18 years of age were recorded in Ireland. Of those, 194 (73%) occurred among children <5 years of age. The median age of patients at admission was 2 years. The average annual KS hospitalization rate for children <5 years of age was 15.2 per 100 000 children, and among that group the hospitalization rate was higher for infants <1 year of age than for children 1 to 4 years of age (19.7 and 16.0 per 100 000 children, respectively). Most KS hospitalizations occurred among children <5 years of age and among boys. The highest monthly number of hospitalizations occurred during the months of November through January. No deaths associated with KS were reported among hospitalized children. Conclusion. Hospital discharge data provide useful information on the epidemiology of KS in Ireland. The hospitalization rate for KS in Ireland is similar to rates in the United States and may be higher than those in other European countries, although the European studies differ in methodologies and time periods.
Revisiting amino acid substitution matrices for identifying distantly related proteins

Motivation: Although many amino acid substitution matrices have been developed, it has not been well understood which is the best for similarity searches, especially for remote homology detection. Therefore, we collected information related to existing matrices, condensed it and derived a novel matrix that can detect more remote homology than ever. Results: Using principal component analysis with existing matrices and benchmarks, we developed a novel matrix, which we designate as MIQS. The detection performance of MIQS is validated and compared with that of existing general purpose matrices using SSEARCH with optimized gap penalties for each matrix. Results show that MIQS is able to detect more remote homology than the existing matrices on an independent dataset. In addition, the performance of our developed matrix was superior to that of CS-BLAST, which was a novel similarity search method with no amino acid matrix. We also evaluated the alignment quality of matrices and methods, which revealed that MIQS shows higher alignment sensitivity than that with the existing matrix series and CS-BLAST. Fundamentally, these results are expected to constitute good proof of the availability and/or importance of amino acid matrices in sequence analysis. Moreover, with our developed matrix, sophisticated similarity search methods such as sequence–profile and profile–profile comparison methods can be improved further. Availability and implementation: Newly developed matrices and datasets used for this study are available at http://csas.cbrc. jp/Ssearch/. Contact: k-tomii@aist.go. jp Supplementary information: Supplementary data are available at Bioinformatics online
Genome-wide co-expression based prediction of differential expressions

MOTIVATION Microarrays have been widely used for medical studies to detect novel disease-related genes. They enable us to study differential gene expressions at a genomic level. They also provide us with informative genome-wide co-expressions. Although many statistical methods have been proposed for identifying differentially expressed genes, genome-wide co-expressions have not been well considered for this issue. Incorporating genome-wide co-expression information in the differential expression analysis may improve the detection of disease-related genes. RESULTS In this study, we proposed a statistical method for predicting differential expressions through the local regression between differential expression and co-expression measures. The smoother span parameter was determined by optimizing the rank correlation between the observed and predicted differential expression measures. A mixture normal quantile-based method was used to transform data. We used the gene-specific permutation procedure to evaluate the significance of a prediction. Two published microarray data sets were analyzed for applications. For the data set collected for a prostate cancer study, the proposed method identified many genes with weak differential expressions. Several of these genes have been shown in literature to be associated with the disease. For the data set collected for a type 2 diabetes study, no significant genes could be identified by the traditional methods. However, the proposed method identified many genes with significantly low false discovery rates. AVAILABILITY The R codes are freely available at http://home.gwu. edu/~ylai/research/CoDiff, where the gene lists ranked by our method are also provided as the Supplementary Material.
Pleiotropic regulatory genes bldA, adpA and absB are implicated in production of phosphoglycolipid antibiotic moenomycin

Unlike the majority of actinomycete secondary metabolic pathways, the biosynthesis of peptidoglycan glycosyltransferase inhibitor moenomycin in Streptomyces ghanaensis does not involve any cluster-situated regulators (CSRs). This raises questions about the regulatory signals that initiate and sustain moenomycin production. We now show that three pleiotropic regulatory genes for Streptomyces morphogenesis and antibiotic production—bldA, adpA and absB—exert multi-layered control over moenomycin biosynthesis in native and heterologous producers. The bldA gene for tRNALeuUAA is required for the translation of rare UUA codons within two key moenomycin biosynthetic genes (moe), moeO5 and moeE5. It also indirectly influences moenomycin production by controlling the translation of the UUA-containing adpA and, probably, other as-yet-unknown repressor gene(s). AdpA binds key moe promoters and activates them. Furthermore, AdpA interacts with the bldA promoter, thus impacting translation of bldA-dependent mRNAs—that of adpA and several moe genes. Both adpA expression and moenomycin production are increased in an absB-deficient background, most probably because AbsB normally limits adpA mRNA abundance through ribonucleolytic cleavage. Our work highlights an underappreciated strategy for secondary metabolism regulation, in which the interaction between structural genes and pleiotropic regulators is not mediated by CSRs. This strategy might be relevant for a growing number of CSR-free gene clusters unearthed during actinomycete genome mining.
Impact of Therapeutic Strategies on the Prognosis of Candidemia in the ICU*

Objectives:To determine the epidemiology of Candida bloodstream infections, variables influencing mortality, and antifungal resistance rates in ICUs in Spain. Design:Prospective, observational, multicenter population-based study. Setting:Medical and surgical ICUs in 29 hospitals distributed throughout five metropolitan areas of Spain. Patients:Adult patients (≥ 18 yr) with an episode of Candida bloodstream infection during admission to any surveillance area ICU from May 2010 to April 2011. Interventions:Candida isolates were sent to a reference laboratory for species identification by DNA sequencing and susceptibility testing using the methods and breakpoint criteria promulgated by the European Committee on Antimicrobial Susceptibility Testing. Prognostic factors associated with early (0–7 d) and late (8–30 d) mortality were analyzed using logistic regression modeling. Measurements and Main Results:We detected 773 cases of candidemia, 752 of which were included in the overall cohort. Among these, 168 (22.3%) occurred in adult ICU patients. The rank order of Candida isolates was as follows: Candida albicans (52%), Candida parapsilosis (23.7%), Candida glabrata (12.7%), Candida tropicalis (5.8%), Candida krusei (4%), and others (1.8%). Overall susceptibility to fluconazole was 79.2%. Cumulative mortality at 7 and 30 days after the first episode of candidemia was 16.5% and 47%, respectively. Multivariate analysis showed that early appropriate antifungal treatment and catheter removal (odds ratio, 0.27; 95% CI, 0.08–0.91), Acute Physiology and Chronic Health Evaluation II score (odds ratio, 1.11; 95% CI, 1.04–1.19), and abdominal source (odds ratio, 8.15; 95% CI, 1.75–37.93) were independently associated with early mortality. Determinants of late mortality were age (odds ratio, 1.04; 95% CI, 1.01–1.07), intubation (odds ratio, 7.24; 95% CI, 2.24–23.40), renal replacement therapy (odds ratio, 6.12; 95% CI, 2.24–16.73), and primary source (odds ratio, 2.51; 95% CI, 1.06–5.95). Conclusions:Candidemia in ICU patients is caused by non-albicans species in 48% of cases, C. parapsilosis being the most common among these. Overall mortality remains high and mainly related with host factors. Prompt adequate antifungal treatment and catheter removal could be critical to decrease early mortality.
Rotated test problems for assessing the performance of multi-objective optimization algorithms

This paper presents four rotatable multi-objective test problems that are designed for testing EMO (Evolutionary Multi-objective Optimization) algorithms on their ability in dealing with parameter interactions. Such problems can be solved efficiently only through simultaneous improvements to each decision variable. Evaluation of EMO algorithms with respect to this class of problem has relevance to real-world problems, which are seldom separable. However, many EMO test problems do not have this characteristic. The proposed set of test problems in this paper is intended to address this important requirement. The design principles of these test problems and a description of each new test problem are presented. Experimental results on these problems using a Differential Evolution Multi-objective Optimization algorithm are presented and contrasted with the Non-dominated Sorting Genetic Algorithm II (NSGA-II).