Miracle-dz/UniFAR-FTUs huggingface dataset:
Dysregulation of gene expression in the R6/2 model of polyglutamine disease: parallel changes in muscle and brain.

Previous analyses of gene expression in a mouse model of Huntington's disease (R6/2) indicated that an N-terminal fragment of mutant huntingtin causes downregulation of striatal signaling genes and particularly those normally induced by cAMP and retinoic acid. The present study expands the regional and temporal scope of this previous work by assessing whether similar changes occur in other brain regions affected in Huntington's disease and other polyglutamine diseases and by discerning whether gene expression changes precede the appearance of disease signs. Oligonucleotide microarrays were employed to survey the expression of approximately 11,000 mRNAs in the cerebral cortex, cerebellum and striatum of symptomatic R6/2 mice. The number and nature of gene expression changes were similar among these three regions, influenced as expected by regional differences in baseline gene expression. Time-course studies revealed that mRNA changes could only reliably be detected after 4 weeks of age, coincident with development of early pathologic and behavioral changes in these animals. In addition, we discovered that skeletal muscle is also a target of polyglutamine-related perturbations in gene expression, showing changes in mRNAs that are dysregulated in brain and also muscle-specific mRNAs. The complete dataset is available at www.neumetrix. info.
Intramural Virtual Electrodes in Ventricular Wall: Effects on Epicardial Polarizations

Background—Intramural virtual electrodes (IVEs) are believed to play an important role in defibrillation, but their existence in intact myocardium remains unproven. Here, IVEs were detected by use of optical recordings of shock-induced transmembrane potential (Vm) changes (ΔVm) measured from the intact epicardial heart surface. Methods and Results—To detect IVEs, isolated porcine left ventricles were sequentially stained with a Vm-sensitive dye by 2 methods: (1) surface staining (SS) and (2) global staining (GS) via coronary perfusion. Shocks (2 to 50 V/cm) were applied across the ventricular wall in an epicardial-to-endocardial direction during the action potential plateau via transparent mesh electrodes, and shock-induced ΔVm were measured optically from the same epicardial locations after SS and GS. Optical recordings revealed significant differences between ΔVm of 2 types that became more prominent with increasing shock strength: (1) for weak shocks, SS-ΔVm were larger and faster than GS-ΔVm; (2) for intermediate shocks, cathodal GS-ΔVm became multiphasic, whereas SS-ΔVm remained monophasic; and (3) for strong shocks, cathodal GS-ΔVm became uniformly negative, whereas SS-ΔVm typically remained positive. The radical differences in the shape and polarity of SS and GS polarizations can be explained by the contribution of subepicardial IVEs to optical signals. Histological examination revealed a dense network of collagen septa in the subepicardium, which could form the IVE substrate. Conclusions—Intramural virtual electrodes are reflected in optical measurements of shock-induced ΔVm on the intact epicardial surface. These IVEs could be a result of microscopic resistive discontinuities formed by collagen septa.
On independent sets in random graphs

The independence number of a sparse random graph G(n,m) of average degree d = 2m/n is well‐known to be (2−εd)nln(d)/d≤α(G(n,m))≤(2+εd)nln(d)/d with high probability, with εd→0 in the limit of large d. Moreover, a trivial greedy algorithm w.h. p. finds an independent set of size nln(d)/d , i.e., about half the maximum size. Yet in spite of 30 years of extensive research no efficient algorithm has emerged to produce an independent set with size (1+ε)nln(d)/d for any fixed ε>0 (independent of both d and n). In this paper we prove that the combinatorial structure of the independent set problem in random graphs undergoes a phase transition as the size k of the independent sets passes the point k∼nln(d)/d . Roughly speaking, we prove that independent sets of size k>(1+ε)nln(d)/d form an intricately rugged landscape, in which local search algorithms seem to get stuck. We illustrate this phenomenon by providing an exponential lower bound for the Metropolis process, a Markov chain for sampling independent sets. © 2014 Wiley Periodicals, Inc. Random Struct. Alg. , 47, 436–486, 2015
Influencing Factors for IT Software Project Failures in Developing Countries - A Critical Literature Survey

Software projects still suffer from high failure rates, especially in developing countries. However, no one evaluated the current studies that were conducted in the context of Saudi Arabia (SA), a developing country. We try to fill this gap using a property-based critical literature survey of existing studies. The findings suggest that management/organization factors including lack of top management support, organizational culture, business process reengineering, lack of training, and unavailability of project management office are main factors that influence software project failures in SA. However, technical and financial factors are secondary; this might be due to the extensive government subsidization for IT. Our analysis can assist software project managers in SA, and it may apply to other developing countries in the Middle East.
[Non-nucleoside reverse transcriptase inhibitors].

The non-nucleoside reverse transcriptase inhibitors (NNRTIs) directly inhibit the HIV-1 reverse transcriptase (RT) by binding in a reversible and non-competitive manner to the enzyme. The currently available NNRTIs are nevirapine, delavirdine, and efavirenz; other compounds are under evaluation. NNRTIs are extensively metabolized in the liver through cytochrome P450, leading to pharmacokinetic interactions with compounds utilizing the same metabolic pathway, particularly PIs, whose plasma levels are altered in the presence of NNRTIs. NNRTIs are drugs with a low genetic barrier, i.e. a single mutation in RT genoma induces a high-level of phenotypic resistance, preventing the use of NNRTIs as monotherapy. In naive patients, several trials have shown the value of NNRTIs in combination with nucleosides and/or protease inhibitors. Small pilot studies have shown that NNRTIs may be useful as second-line therapy. However, due to the rapid emergence of resistant virus to these compounds in case of incomplete viral suppression, NNRTIs should not be added to current failing antiretroviral regimen. The most common side-effect reported with nevirapine and delavirdine is rash. The incidence of rash is rather similar under these two compounds, but severe rash is less frequent with delavirdine. The most common adverse reactions reported with efavirenz are central nervous system complaints such as dizziness. Rash is reported less frequently than with nevirapine or delavirdine, and is usually mild. NNRTIs resistance mutations are located in the amino acid residues aligning the NNRTI-binding "pocket" site. High-level resistance is often associated with a single point mutation which develops within this site (especially codon groups 100 - 108 and 181 - 190). Patients failing on one NNRTI are very likely to possess multiple NNRTI resistance mutations. NNRTIs should always be used as part of a potent antiretroviral therapy to insure suppression of viral replication, thus circumventing the rapid selection of cross-resistant variants.
Geometric and Cohomological Methods in Group Theory: Constructing non-positively curved spaces and groups

The theory of non-positively curved spaces and groups is tremendously powerful and has enormous consequences for the groups and spaces involved. Nevertheless, our ability to construct examples to which the theory can be applied has been severely limited by an inability to test – in real time – whether a random finite piecewise Euclidean complex is non-positively curved. In this article I focus on the question of how to construct examples of nonpositively curved spaces and groups, highlighting in particular the boundary between what is currently do-able and what is not yet feasible. Since this is intended primarily as a survey, the key ideas are merely sketched with references pointing the interested reader to the original articles. Over the past decade or so, the consequences of non-positive curvature for geometric group theorists have been throughly investigated, most prominently in the book by Bridson and Haefliger [26]. See also the recent review article by Kleiner in the Bulletin of the AMS [59] and the related books by Ballmann [4], BallmannGromov-Schroeder [5] and the original long article by Gromov [48]. In this article I focus not on the consequences of the theory, but rather on the question of how to construct examples to which it applies. The structure of the article roughly follows the structure of the lectures I gave during the Durham symposium with the four parts corresponding to the four talks. Part 1 introduces the key problems and presents some basic decidability results, Part 2 focuses on practical algorithms and low-dimensional complexes, Part 3 presents case studies involving special classes of groups such as Artin groups, small cancellation groups and ample-twisted face pairing 3-manifolds. In Part 4 I explore the weaker notion of conformal non-positive curvature and introduce the notion of an angled n-complex. As will become clear, the topics covered have a definite bias towards research in which I have played some role. These are naturally the results with which I am most familiar and I hope the reader will pardon this lack of a more impartial perspective. Part 1. Negative curvature Although the definitions of δ-hyperbolic and CAT(0) spaces / groups are wellknown, it is perhaps under-appreciated that there are at least seven potentially distinct classes of groups which all have some claim to the description “negativelycurved. ” Sections 1 and 2 briefly review the definitions needed in order to describe these classes, the known relationships between them, and the current status of the (rather optimisitic) conjecture that all seven of these classes are identical. Since the emphasis in this article is on the construction of examples, finite piecewise Date: August 9, 2004. Partially supported by NSF grant no. DMS-0101506
The Central Italy Seismic Sequence between August and December 2016: Analysis of Strong‐Motion Observations

ABSTRACT Since August 2016, central Italy has been struck by one of the most important seismic sequences ever recorded in the country. In this study, a strong‐motion data set, consisting of nearly 10,000 waveforms, has been analyzed to gather insights about the main features of ground motion, in terms of regional variability, shaking intensity, and near‐source effects. In particular, the shake maps from the three main events in the sequence have been calculated to evaluate the distribution of shaking at a regional scale, and a residual analysis has been performed, aimed at interpreting the strong‐motion parameters as functions of source distance, azimuth, and local site conditions. Particular attention has been dedicated to near‐source effects (i.e., hanging wall/footwall, forward‐directivity, or fling‐step effects). Finally, ground‐motion intensities in the near‐source area have been discussed with respect to the values used for structural design. In general, the areas of maximum shaking appear to reflect, primarily, rupture complexity on the finite faults. Large ground‐motion variability is observed along the Apennine direction (northwest–southeast) that can be attributed to source‐directivity effects, especially evident in the case of small‐magnitude aftershocks. Amplifications are observed in correspondence to intramountain basins, fluvial valleys, and the loose deposits along the Adriatic coast. Near‐source ground motions exhibit hanging‐wall effects, forward‐directivity pulses, and permanent displacement.
Effects of absorption enhancer surfactants on culture models of intestinal and vascular barriers

Surfactants used in pharmaceutical products have several advantageous properties; they improve drug absorption and dissolution, and protect active molecules. However, adverse effects are also observed during the application of different surface active agents which necessitates the investigation of registered surfactants and novel absorption enhancer candidates. Cremophor RH40 and EL are widely used excipients in oral and intravenous drug formulations. Studies indicate that Cremophors, especially EL, have toxic side effects, but few data are available on endothelial and epithelial cells which form biological barriers and are directly exposed to these molecules. In our investigation human intestinal epithelial and vascular endothelial cells were treated with Cremophor RH40 and EL in clinically relevant concentrations and their toxic effect was monitored by several methods. Cremophors caused concentration- and time-dependent damage in both epithelial and endothelial cells. Endothelial cells were more sensitive to surfactant treatment than epithelial cells, and Cremophor EL was more toxic than RH40 in both cell types. Our results support and complement the previously experimentally described toxic effects of Cremophor EL which may be related to the clinically recognized side-effects of medicines containing Cremophor EL. Sucrose fatty acid esters are increasingly investigated as novel excipients in pharmaceutical research and some of them are registered in Pharmacopoeias both in the European Union and in the United States. Several studies documented their advantageous properties but few data are available on their toxicity profile, mode of action and efficacy on intestinal epithelial models. Three water soluble sucrose esters, palmitate (P-1695), myristate (M-1695), laurate (D-1216), and two reference absorption enhancers, Tween 80 and Cremophor RH40 were tested on human Caco-2 intestinal epithelial cells. Sucrose esters in non-toxic concentrations significantly reduced resistance and impedance of cells, but not reference surfactants. All excipients increased permeability for drugs and fluidized plasma membrane, but did not visibly open tight junctions. Tween 80 but not sucrose esters inhibit P-glycoprotein. Our data indicate that in addition to their dissolution increasing properties sucrose esters can enhance drug permeability through both the transcellular and paracellular routes but this effect is unrelated to P-glycoprotein inhibition. The presented results demonstrate the differences between the cellular actions of various non-ionic surfactant excipients, which can be important for the development of new pharmaceutical formulations and drug delivery systems.
Self-Reported Non-Celiac Wheat Sensitivity in High School Students: Demographic and Clinical Characteristics

Background: Non-Celiac Wheat Sensitivity (NCWS) has recently been included among the gluten-related disorders. As no biomarkers of this disease exist, its frequency has been estimated based on self-reported symptoms, but to date no data are available about self-reported NCWS in teenagers. Aim: To explore the prevalence of self-reported NCWS in a group of high school students and to study their demographic and clinical characteristics. Methods: The study was performed between April 2015 and January 2016 in two high schools of a coastal town in the south of Sicily (Italy). A total of 555 students (mean age 17 years, 191 male, 364 female) completed a modified validated questionnaire for self-reported NCWS. The subjects who self-reported NCWS were then compared with all the others. Results: Seven individuals (1.26%) had an established diagnosis of CD. The prevalence of self-reported NCWS was 12.2%, and 2.9% were following a gluten-free diet (GFD). Only 15 out of 68 (23%) NCWS self-reporters had consulted a doctor for this problem and only nine (14%) had undergone serological tests for celiac disease. The NCWS self-reporters very often had IBS symptoms (44%). Conclusions: Self-reported NCWS was found to be common in teenagers, with a frequency of 12.2%; the frequency of GFD use was 2.9%, which was much higher than the percentage of known CD in the same population (1.26%). A greater awareness of the possible implications on the part of the subjects involved, and a more thorough medical approach to the study of self-reported wheat-induced symptoms are required.
Differential inhibition of the initiation of DNA replication in stringent and relaxed strains of Escherichia coli.

Starvation for isoleucine inhibits chromosome, minichromosome and pBR322 DNA replication in a stringent strain of E. coli , but does not do so in a relaxed mutant. Starvation for other amino acids inhibits either chromosome and minichromosome replication in both strains. From these results we conclude that oriC and pBR322 replication are stringently regulated and that isoleucine seems not to be essential for the protein synthesis required at the initiation of oriC replication. Deprivation of isoleucine in a Rel − strain gives rise to amplification of minichromosome and pBR322 with a better yield of the latter plasmid than that following treatment with chloramphenicol.
No sex in fungus-farming ants or their crops

Asexual reproduction imposes evolutionary handicaps on asexual species, rendering them prone to extinction, because asexual reproduction generates novel genotypes and purges deleterious mutations at lower rates than sexual reproduction. Here, we report the first case of complete asexuality in ants, the fungus-growing ant Mycocepurus smithii, where queens reproduce asexually but workers are sterile, which is doubly enigmatic because the clonal colonies of M. smithii also depend on clonal fungi for food. Degenerate female mating anatomy, extensive field and laboratory surveys, and DNA fingerprinting implicate complete asexuality in this widespread ant species. Maternally inherited bacteria (e.g. Wolbachia, Cardinium) and the fungal cultivars can be ruled out as agents inducing asexuality. M. smithii societies of clonal females provide a unique system to test theories of parent–offspring conflict and reproductive policing in social insects. Asexuality of both ant farmer and fungal crop challenges traditional views proposing that sexual farmer ants outpace coevolving sexual crop pathogens, and thus compensate for vulnerabilities of their asexual crops. Either the double asexuality of both farmer and crop may permit the host to fully exploit advantages of asexuality for unknown reasons or frequent switching between crops (symbiont reassociation) generates novel ant–fungus combinations, which may compensate for any evolutionary handicaps of asexuality in M. smithii.
Prognostic significance of circulating microsatellite markers in the plasma of melanoma patients.

PURPOSE Multiple genetic alterations including loss of heterozygosity (LOH) occur commonly in melanoma tumors. We demonstrated previously free-circulating DNA microsatellites with LOH in the blood of melanoma patients. These LOH markers in plasma may be useful as surrogates for subclinical disease progression. The purpose of this study was to determine whether the presence of circulating tumor microsatellite markers in the preoperative blood from patients with melanoma has prognostic utility. EXPERIMENTAL DESIGN Plasma was analyzed for the presence of LOH at six chromosome regions, which are common for allelic loss in melanoma tumors, in 57 patients undergoing surgical resection of all of the clinically apparent disease. RESULTS LOH was detected in 32 of 57 patients (56%). Both LOH incidence and frequency correlated with advancing American Joint Committee on Cancer stage. In patients with American Joint Committee on Cancer stage III, the presence of LOH as an independent variable in preoperative plasma was significantly associated (P = 0.05) with an increased risk of death. Furthermore, LOH at microsatellite marker D1S228 in the plasma of patients with advanced disease correlated significantly (P = 0.0009) with a poorer survival after surgical resection. LOH commonly found in melanoma tumors can be successfully identified in the plasma of a patient, providing a potentially less invasive route for following genetic changes that serve as molecular surrogates for assessing subclinical disease progression. CONCLUSIONS This study provides evidence that blood testing for circulating tumor genetic markers may provide valuable prognostic information and guide future therapy.
Over-the-cell channel routing

A common approach to the over-the-cell channel routing problem is to divide the problem into three steps: (1) routing over the cells, (2) choosing net segments, (3) routing within the channel. It is shown that the first step can be reduced to the problem of finding a maximum independent set of a circle graph and thus can be solved optimally in O(n/sup 2/) time. It is also shown that to determine an optimal choice of net segments in the second step is NP-hard in general, and an efficient heuristic algorithm for this step is presented. The third step can be done easily using a conventional channel router. Based on these theoretical results, an over-the-cell channel router was designed which produces better solutions than by the over-the-cell router of Y. Shiraishi and Y. Sakemi (IEEE Trans. Computer-Aided Design, vol.6, no.3, p.462-71, 1987). <<ETX>>
AspectMatlab: an aspect-oriented scientific programming language

This paper introduces a new aspect-oriented programming language, AspectMatlab. Matlab® is a dynamic scientific programming language that is commonly used by scientists because of its convenient and high-level syntax for arrays, the fact that type declarations are not required, and the availability of a rich set of application libraries. AspectMatlab introduces key aspect-oriented features in a way that is both accessible to scientists and where the aspect-oriented features concentrate on array accesses and loops, the core computation elements in scientific programs. Introducing aspects into a dynamic language such as Matlab also provides some new challenges. In particular, it is difficult to statically determine precisely where patterns match, resulting in many dynamic checks in the woven code. Our compiler includes flow analyses which are used to eliminate many of those dynamic checks. This paper reports on the language design of AspectMatlab, the amc compiler implementation and related optimizations, and also provides an overview of use cases that are specific to scientific programming.
Relationship between Physical Parameters of Various Metal Ions and Binding Affinity for Alginate.

We investigated the relationship between the physical parameters of various metal ions, including toxic metal ions, and the binding affinity of these metal ions for alginate (Alg). The binding constant, K, of Sr2+ was the highest among all tested metal ions. The order of K values was: Sr2+>Pb2+>Tb3+>Dy3+>Ca2+>Cd2+>Mg2+>Fe2+>Fe3+>Co2+>Al3+>Ni2+>Cs+>Cu2+>Ag+>Li+>K+. The metal ions showing the highest K values had ionic radii within the range of about 90-120 pm. Moreover, the K values of divalent or trivalent metal ions tended to be higher than those of monovalent ions. The number of binding sites per 1 mg of Alg (n) was highest for K+, followed by Pb2+ and Cs+. The order of affinity (calculated as the product of n and K) was Pb2+>Dy3+>Tb3+>Sr2+>Ca2+>Mg2+>Cd2+>Fe2+, Fe3+>Cs+>Al3+>Co2+>Ni2+>Cu2+>Ag+>K+>Li+. Our results support the idea that Alg would be effective as an excretion accelerator and/or absorption inhibitor for various toxic metal ions.