Miracle-dz/UniFAR-FTUs huggingface dataset:
Screening Respiratory Samples for Detection of Human Rhinoviruses (HRVs) and Enteroviruses: Comprehensive VP4-VP2 Typing Reveals High Incidence and Genetic Diversity of HRV Species C

ABSTRACT Rhinovirus infections are the most common cause of viral illness in humans, and there is increasing evidence of their etiological role in severe acute respiratory tract infections (ARTIs). Human rhinoviruses (HRVs) are classified into two species, species A and B, which contain over 100 serotypes, and a recently discovered genetically heterogeneous third species (HRV species C). To investigate their diversity and population turnover, screening for the detection and the genetic characterization of HRV variants in diagnostic respiratory samples was performed by using nested primers for the efficient amplification of the VP4-VP2 region of HRV (and enterovirus) species and serotype identification. HRV species A, B, and C variants were detected in 14%, 1.8%, and 6.8%, respectively, of 456 diagnostic respiratory samples from 345 subjects (6 samples also contained enteroviruses), predominantly among children under age 10 years. HRV species A and B variants were remarkably heterogeneous, with 22 and 6 different serotypes, respectively, detected among 73 positive samples. Similarly, by using a pairwise distance threshold of 0.1, species C variants occurring worldwide were provisionally assigned to 47 different types, of which 15 were present among samples from Edinburgh, United Kingdom. There was a rapid turnover of variants, with only 5 of 43 serotypes detected during both sampling periods. By using divergence thresholds and phylogenetic analysis, several species A and C variants could provisionally be assigned to new types. An initial investigation of the clinical differences between rhinovirus species found HRV species C to be nearly twice as frequently associated with ARTIs than other rhinovirus species, which matches the frequencies of detection of respiratory syncytial virus. The study demonstrates the extraordinary genetic diversity of HRVs, their rapid population turnover, and their extensive involvement in childhood respiratory disease.
High Spicy Food Intake and Risk of Cancer: A Meta-analysis of Case–control Studies

Background: Studies on the association between spicy food intake and cancer risk have reported inconsistent results. We quantitatively assessed this association by conducting a meta-analysis based on evidence from case–control studies. Methods: PubMed, EMBASE, and the Cochrane Library were searched for eligible publications. Combined odds ratios (ORs) with their 95% confidence interval (CI) were calculated using a random- or fixed-effects model. The methodological quality of the included articles was assessed using the Newcastle–Ottawa scale (NOS). All data were analyzed using STATA 11.0 software (version 11.0; StataCorp., College Station, TX, USA). Subgroup analyses were also performed with stratification by region, sex, number of cases, cancer subtype, source of the control group, and NOS score. Results: A total 39 studies from 28 articles fulfilled the inclusion criteria for the meta-analysis (7884 patients with cancer and 10,142 controls). Comparison of the highest versus lowest exposure category in each study revealed a significant OR of 1.76 (95% CI = 1.35–2.29) in spite of significant heterogeneity (P < 0.001). In the subgroup analyses, this positive correlation was still found for gastric cancer, different regions, different numbers of cases, different sources of the control group, and high-quality articles (NOS score of ≥ 7). However, no statistically significant association was observed for women, esophageal cancer, gallbladder cancer, or low-quality articles (NOS score of <7). No evidence of publication bias was found. Conclusions: Evidence from case–control studies suggested that a higher level of spicy food intake may be associated with an increased incidence of cancer despite significant heterogeneity. More studies are warranted to clarify our understanding of the association between high spicy food intake and the risk of cancer.
A FUNCTIONAL CLASSIFICATION SYSTEM OF THE VISUALLY IMPAIRED TO REPLACE THE LEGAL DEFINITION OF BLINDNESS*

&NA; A discussion of the legal definition of blindness is given and some of its shortcomings are revealed. This is followed by the development of a functional classification system of the visually impaired which divides that population into four categories, namely, (1) the functionally blind, (2) the functionally sighted, (3) the functionally sighted with aided mobility, and (4) the functionally sighted with neither sighted literacy nor sighted illiteracy. The need for a functional classification system is then argued. This includes a discussion of the current plight of the visually impaired. Emphasis is placed upon the unfortunate consequences that have arisen as a result of (1) a failure on the part of the general public, as well as many officials of public and private organizations that serve “the blind,” to recognize the heterogeneity of the visually impaired population and (2) the misapplication of the legal definition of blindness. Recommendations are then made which the author believes will tend to clarify the nature of the visually impaired population, improve public understanding of the capabilities and needs of its members, improve the quality and quantity of the services they receive from public and private organizations, and increase their chances of receiving a high quality and relevant education and achieving economic independence.
VE‐Cadherin‐Cre‐recombinase transgenic mouse: A tool for lineage analysis and gene deletion in endothelial cells

The ability to target gene deletion to a specific cellular compartment via the Cre/loxP system has been a powerful tool in the analysis of broadly expressed genes. Here, we report the generation of a transgenic mouse line in which expression of Cre‐recombinase is under the regulatory control of the VE‐Cadherin promoter. Temporal distribution and activity of the enzyme was evaluated with two independent Cre reporter lines. Histological analysis was performed throughout development and in the adult. Recombination of lox P sites with subsequent expression of β‐galactosidase or GFP was detected as early as E7.5 in endothelial cells of the yolk sac. Progressive staining of the embryonic vasculature was noted from E8.5–13.5; however, more contiguous reporter expression was only seen by E14.5 onward in all endothelial compartments including arteries, veins, and capillaries. In addition, we found Cre activity in lymphatic endothelial cells. Unlike other endothelial‐specific Cre mice, this model showed expression in the adult quiescent vasculature. Furthermore, the constitutive nature of the VE‐Cadherin promoter in the adult can be advantageous for analysis of gene deletion in pathological settings. Developmental Dynamics 235:759–767, 2006. © 2006 Wiley‐Liss, Inc.
Nicotinic acetylcholine receptors on local circuit neurons in the dentate gyrus: a potential role in the regulation of granule cell excitability

Abbreviated title: Alpha7-containing nAChRs in rat dentate gyrus Abstract Although the dentate gyrus is one of the primary targets of septo-hippocampal cholinergic afferents, relatively little is known about the cholinergic physiology of neurons in the area. By combining whole-cell-patch-clamp recording with brief local application of exogenous agonists in horizontal slices, we found that there is robust expression of functional somatic α7-containing nAChRs on molecular layer interneurons, hilar interneurons, and the glutamatergic mossy cells of the dentate hilus. In contrast, the principle output neurons of the dentate gyrus, the granule cells, are generally unresponsive to focal somatic or dendritic application of acetylcholine (ACh) in the presence of atropine. We also demonstrate that cholinergic activation of α7-containing nAChRs on the subgranular interneurons of the hilus can produce methyllycaconitine (MLA) sensitive GABAergic inhibitory postsynaptic currents (IPSCs) in nearby granule cells and enhance the amplitude of an electrically evoked monosynaptic IPSC. Further, activation of α7-containing nAChRs on subgranular interneurons that is timed to coincide with synaptic release of glutamate onto these cells will enhance the functional inhibition of granule cells. These findings suggest that a complex interplay between glutamatergic afferents from the entorhinal cortex and cholinergic afferents from the medial septum could be involved in the normal regulation of granule cell function. Such a relationship between these two afferent pathways could be highly relevant to the study of both age-related memory dysfunction, and disorders involving regulation of excitability, such as temporal lobe epilepsy.
The 30-Year Natural History of Type 1 Diabetes Complications

Declining incidences in Europe of overt nephropathy, proliferative retinopathy, and mortality in type 1 diabetes have recently been reported. However, comparable data for the U.S. and trend data for neuropathy and macrovascular complications are lacking. These issues are addressed using the prospective observational Pittsburgh Epidemiology of Childhood-Onset Diabetes Complications Study. Participants were stratified into five cohorts by diagnosis year: 1950–1959, 1960–1964, 1965–1969, 1970–1974, and 1975–1980. Mortality, renal failure, and coronary artery disease (CAD) status were determined on the complete cohort (n = 906) at 20, 25, and 30 years. Overt nephropathy, proliferative retinopathy, and neuropathy were assessed at 20 and 25 years on the subset of participants with a clinical examination. There was a decreasing trend by diagnosis year for mortality, renal failure, and neuropathy across all time intervals (P < 0.05), with the 1950–1959 cohort having a fivefold higher mortality at 25 years than the 1970s’ cohorts. Proliferative retinopathy and overt nephropathy showed nonsignificant declines at 20 years (P < 0.16 and P < 0.13, respectively) and no change at 25 years. CAD event rates, which were lower than the other complications, also showed no trend. Although some type 1 diabetes complications (mortality, renal failure, and neuropathy) are declining, others (CAD, overt nephropathy, and proliferative retinopathy) show less favorable changes by 30 years.
Learning Rule Ensembles for Ordinal Classification with Monotonicity Constraints

Ordinal classification problems with monotonicity constraints (also referred to as multicriteria classification problems) often appear in real-life applications, however, they are considered relatively less frequently in theoretical studies than regular classification problems. We introduce a rule induction algorithm based on the statistical learning approach that is tailored for this type of problems. The algorithm first monotonizes the dataset (excludes strongly inconsistent objects), using Stochastic Dominance-based Rough Set Approach, and then uses forward stagewise additive modeling framework for generating a monotone rule ensemble. Experimental results indicate that taking into account knowledge about order andmonotonicity constraints in the classifier can improve the prediction accuracy.
Social Networks and Social Movements: A Microstructural Approach to Differential Recruitment

Past examinations of differential recruitment to and the differential growth of social movements have typically sought explanation at a social psychological/motivational level of analysis. That focus has recently been called into question by scholars concerned with the process through which movement organizations expand their ranks and mobilize support for their causes. Yet, as Useem (1975) and Zald and McCarthy (1979) have noted, there has been little systematic research conducted on the details of the influence process. Drawing on data derived from a synthesis of existing research and two primary sources, this paper attempts to shed greater empirical and theoretical light on the movement recruitment process. The findings indicate that differential recruitment is not merely a function of dispositional susceptibility, but is strongly influenced by structural proximity, availability, and affective interaction with movement members. The findings also indicate that a movement organization's network attributes function as an important determinant of its recruitment strategies and growth.
Local anesthetics induce a decrease in the levels of glucose 1, 6-bisphosphate, fructose 1,6-bisphosphate, and ATP, and in the viability of melanoma cells.

Glycolysis is known to be the primary energy source in cancer cells. We investigated here the effect of local anesthetics, lidocaine and bupivacaine, on the levels of glucose 1,6-bisphosphate and fructose 1,6-bisphosphate, the two stimulatory signal molecules of glycolysis, and on ATP levels and cell viability in B16 melanoma cells. We found that both drugs induced a significant, dose-dependent reduction in the levels of glucose 1,6-bisphosphate, fructose 1, 6-bisphosphate, ATP, and cell viability. Bupivacaine was more potent than lidocaine. The decrease in glucose 1,6-bisphosphate and fructose 1,6-bisphosphate, induced by the local anesthetics, preceded the reduction in the viability of melanoma cells, indicating that these are early changes and not a result of cell death. Cell viability was reduced in a close correlation with the fall in ATP. These findings suggest that the fall in the levels of the two signal allosteric regulators of glycolysis, induced by the local anesthetics, is one of the mechanisms that causes a reduction in glycolysis and ATP levels, which eventually leads to melanoma cell death. These experiments suggest that local anesthetics, and especially bupivacaine, are most promising agents in the treatment of melanoma.
Integrative network alignment reveals large regions of global network similarity in yeast and human

MOTIVATION High-throughput methods for detecting molecular interactions have produced large sets of biological network data with much more yet to come. Analogous to sequence alignment, efficient and reliable network alignment methods are expected to improve our understanding of biological systems. Unlike sequence alignment, network alignment is computationally intractable. Hence, devising efficient network alignment heuristics is currently a foremost challenge in computational biology. RESULTS We introduce a novel network alignment algorithm, called Matching-based Integrative GRAph ALigner (MI-GRAAL), which can integrate any number and type of similarity measures between network nodes (e.g. proteins), including, but not limited to, any topological network similarity measure, sequence similarity, functional similarity and structural similarity. Hence, we resolve the ties in similarity measures and find a combination of similarity measures yielding the largest contiguous (i.e. connected) and biologically sound alignments. MI-GRAAL exposes the largest functional, connected regions of protein-protein interaction (PPI) network similarity to date: surprisingly, it reveals that 77.7% of proteins in the baker's yeast high-confidence PPI network participate in such a subnetwork that is fully contained in the human high-confidence PPI network. This is the first demonstration that species as diverse as yeast and human contain so large, continuous regions of global network similarity. We apply MI-GRAAL's alignments to predict functions of un-annotated proteins in yeast, human and bacteria validating our predictions in the literature. Furthermore, using network alignment scores for PPI networks of different herpes viruses, we reconstruct their phylogenetic relationship. This is the first time that phylogeny is exactly reconstructed from purely topological alignments of PPI networks. AVAILABILITY Supplementary files and MI-GRAAL executables: http://bio-nets.doc. ic.ac. uk/MI-GRAAL/.
Rotary and radial forcing effects on center-of-mass locomotion dynamics

Rotary and radial forcing are two common actuation methods for legged robots. However, these two orthogonal methods of center-of-mass (CoM) forcing have not been compared as potentially alternative strategies of actuation. In this paper, we compare the CoM stability and energetics of running with rotary and radial actuation through the simulation of two models: the rotary-forced spring-loaded inverted pendulum (rotary-forced-SLIP), and the radially-forced-SLIP. We model both radial and rotary actuation in the simplest way, applying them as a constant force during the stance portion of the gait. A simple application of constant rotary forcing throughout stance is capable of producing fully-asymptotically stable motion; however, a similarly constant application of radial forcing throughout the stance is not capable of producing stable solutions. We then allow both the applied rotary and radial forcing functions to turn on or off based on the occurrence of the mid-stance event, which breaks the symmetry of actuation during stance towards a net forward propulsion. We find that both a rotary force applied in the first half of stance and a radial force applied in the second half of stance, are capable of stabilizing running. Interestingly, these two forcing methods improve the motion stability in different ways. Rotary forcing first reduces then greatly increases the size of the stable parameter region when gradually increased. Radial forcing expands the stable parameter region, but only in a moderate way. Also, it is found that parameter region stabilized by rotary and radial forcing are largely complementary. Overall, rotary forcing can better stabilize running for both constant and event-based forcing functions that were attempted. This indicates that rotary forcing has an inherent capability of stabilizing running, even when minimal time-or-event-or-state feedback is present. Radial forcing, however, tends to be more energy efficient when compared to rotary forcing. In addition, a balanced stability and energy efficiency can be achieved by combining both forcing methods. These results may be applied in the future study of how legged animals move.
Transcriptional Repression Mediated by the KRAB Domain of the Human C2H2 Zinc Finger Protein Kox1/ZNF10 Does Not Require Histone Deacetylation

Abstract The KRAB domain of human Kox1, a member of the KRAB C2H2 zinc finger family, confers strong transcriptional repressor activities even to remote promoter positions. Here, HDAC inhibitors were used to demonstrate that histone deacetylation is not required for mediating transcriptional repression of KRAB zinc finger proteins. Two reporter systems with either stably integrated or transiently transfected templates, both under control of strong viral promoters, were analyzed. Under all circumstances, HDAC inhibition did not alter the repression potential of the KRAB domain. In case of the stably integrated luciferase reporter gene system, neither expression levels of the KRAB fusion protein nor complex formation with its putative corepressor TIF1β were significantly changed. Furthermore, the TIF1β/KRAB complex was devoid of mSin3A and HDAC1. In the transient transfection system, the transcriptional repression induced by TIF1β and HP1α was not diminished by HDAC inhibitors, whereas the repressory activity of TIF1α was significantly affected. Thus, KRAB, TIF1β and HP1α are likely to be functionally linked. In conclusion, HDAC activity is not essential for the strong transcriptional repressor activity mediated by the KRAB domain of Kox1 in particular and, presumably, by KRAB domains in general. This feature might be helpful in identifying and characterizing target genes under the control of KRAB zinc finger proteins.
Cosmic-Ray Acceleration at the Forward Shock in Tycho’s Supernova Remnant: Evidence from Chandra X-Ray Observations

We present evidence for cosmic-ray acceleration at the forward shock in Tycho's supernova remnant (SNR) from three X-ray observables: (1) the proximity of the contact discontinuity to the forward shock, or blast wave, (2) the morphology of the emission from the rim of Tycho, and (3) the spectral nature of the rim emission. We determine the locations of the blast wave (BW), contact discontinuity (CD), and reverse shock (RS) around the rim of Tycho's supernova remnant using a principal component analysis and other methods applied to new Chandra data. The azimuthal-angle-averaged radius of the BW is 251''. For the CD and RS we find average radii of 241'' and 183'', respectively. Taking account of projection effects, we find ratios of 1 : 0.93 : 0.70 (BW : CD : RS). We show these values to be inconsistent with adiabatic hydrodynamic models of SNR evolution. The CD : BW ratio can be explained if cosmic-ray acceleration of ions is occurring at the forward shock. The RS : BW ratio, as well as the strong Fe Kα emission from the Tycho ejecta, imply that the RS is not accelerating cosmic rays. We also extract radial profiles from ~34% of the rim of Tycho and compare them to models of surface brightness profiles behind the BW for a purely thermal plasma with an adiabatic shock. The observed morphology of the rim is much more strongly peaked than predicted by the model, indicating that such thermal emission is implausible here. Spectral analysis also implies that the rim emission is nonthermal in nature, lending further support to the idea that Tycho's forward shock is accelerating cosmic rays.
V&V through inconsistency tracking and analysis

In this paper we describe a research agenda for a study into the use of inconsistency analysis as a tool for software V&V and in particular, the use of category theory as a basis for modeling consistency relationships between the various artifacts of software development, including specifications, design, test cases, etc. Our expectation is that inconsistency analysis is fundamental to much of the work of V&V and that a systematic approach will have impacts across a wide range of V&V tasks. Two goals are described: an account of the contribution of inconsistency analysis to various V&V analyses, and the development of a formal framework for inconsistency analysis. Our approach to the development of the latter is through the refinement of the viewpoint framework using the language of category theory. We discuss the relationship between specification morphisms, as conventional conceived in work on composition of specifications, and inter-viewpoint consistency relationships. We conclude that inconsistency analysis has the potential to address the 'air gaps' between methods used during the various phases of the software lifecycle.
Different genotype pattern of varicella‐zoster virus obtained from patients with varicella and zoster in Germany

The general use of the varicella vaccine requires the surveillance of varicella‐zoster virus (VZV) strains in patients infected with VZV. This paper reports the data achieved from a prospective study of genotyping VZV in Germany, analyzing the restriction fragment length polymorphism (RFLP) of the open reading frames (ORF) 38, 54, and 62 as well as the polymorphism of the R5 repeat region. The study included 177 patients with varicella. Seventy‐eight patients with zoster served as controls. Results revealed that 78% of VZV strains in patients with varicella had the genetic profile of the dominant wild‐genotype occurring in Europe and 22% had the markers of African or Asian strains. Varicella patients with the profile of African or Asian strains were significantly younger than patients with varicella caused by the dominant genotype. By contrast, all zoster patients exhibited strains representing the majority of wild‐type strains in Europe. In conclusion, VZV strains from patients with varicella have a significantly higher genetic variability than viral strains from zoster patients. Since variants with the markers of African or Asian strains could only be found in young children with chickenpox, the results suggest a changing scene of VZV genotypes in Germany. As reasons, the spread of viruses, which may be imported originally by persons immigrating from warmer climates, or the recombination between wild‐and vaccine‐type viruses have to be considered. J. Med. Virol. 79:1025‐1031, 2007. © 2007 Wiley‐Liss, Inc.