Miracle-dz/UniFAR-FTUs huggingface dataset:
Apolipoprotein E*4 (APOE*4) Genotype Is Associated with Altered Levels of Glutamate Signaling Proteins and Synaptic Coexpression Networks in the Prefrontal Cortex in Mild to Moderate Alzheimer Disease*

It has been hypothesized that Alzheimer disease (AD) is primarily a disorder of the synapse. However, assessment of the synaptic proteome in AD subjects has been limited to a small number of proteins and often included subjects with end-stage pathology. Protein from prefrontal cortex gray matter of 59 AD subjects with mild to moderate dementia and 12 normal elderly subjects was assayed using targeted mass spectrometry to quantify 191 synaptically expressed proteins. The profile of synaptic protein expression clustered AD subjects into two groups. One of these was characterized by reduced expression of glutamate receptor proteins, significantly increased synaptic protein network coexpression, and associated withApolipoprotein E*4 (APOE*4) carrier status. The second group, by contrast, showed few differences from control subjects. A subset of AD subjects had altered prefrontal cortex synaptic proteostasis for glutamate receptors and their signaling partners. Efforts to therapeutically target glutamate receptors in AD may have outcomes dependent on APOE*4 genotype.
Control of GaAs nanowire morphology and crystal structure

The morphology and crystal structure of Au-seeded GaAs nanowires (NWs) grown by molecular beam epitaxy were investigated as a function of the temperature, V/III flux ratio, and Ga flux. Low and intermediate growth temperatures of 400 and 500 °C resulted in a strongly tapered morphology, with stacking faults occurring at an average rate of 0.1 nm−1. NWs with uniform diameter and the occurrence of crystal defects reduced by more than an order of magnitude were achieved at 600 °C, a V/III flux ratio of 2.3, and a Ga impingement rate on the surface of 0.07 nm s−1. Comparison of nanowire densities on the various post-growth surfaces suggests a possible incubation time between the moment the Ga shutter is opened and when nanowire growth is initiated. Increasing the flux ratio favored uniform sidewall growth, making the process suitable for the fabrication of core–shell structures.
Long Noncoding RNA CPS1-IT1 Suppresses Cell Proliferation and Metastasis in Human Lung Cancer

The long noncoding CPS1 intronic transcript 1 (lncRNA CPS1-IT1) is a recently identified tumor suppressor in the lncRNA family of proteins. Whether this lncRNA plays any functional role in solid tumors remains largely unknown. The present study aimed to investigate the role of lncRNA CPS1-IT1 in human lung cancer. Expression of lncRNA CPS1-IT1 was initially assessed in human lung cancer and in a series of lung cancer cell lines. The effects of CPS1-IT1 overexpression on cell proliferation, migration, and invasion were examined in lung cancer cell lines A549 and 95D. It was found that lncRNA CPS1-IT1 was significantly lower in cancerous tissues than in noncancerous tissues. lncRNA CPS1-IT1 was differentially expressed in lung cancer cell lines and expressed the least in two highly invasive cell lines, A549 and 95D. Overexpression of CPS1-IT1 slowed down cell proliferation by 35.7% in A549 cells and 30.8% in 95D cells on the fifth day. Cell migration was inhibited by 59% in A549 cells and 48% in 95D cells, and cell invasion was suppressed by 60% in both cell lines after overexpression of CPS1-IT1. While cell apoptosis was induced, CPS1-IT1 overexpression promoted the activities of caspase 3 and caspase 9 without affecting that of caspase 8. These observations were suggestive of the tumor-suppressive role of lncRNA CPS1-IT1 in lung cancer. Our data suggest that CPS1-IT1 may be used as a biomarker for early diagnosis and therapeutic targets against lncRNA and may be promising in the treatment of lung cancer.
Miniaturized compensated quasi-lumped wideband Marchand balun

In this paper, a miniaturized wideband Marchand balun with separated differential output designed with the use of quasi-lumped element technique has been proposed. The circuit utilizes multi-compensation technique together with folded coupled inductors to obtain high performance and reduced size by appropriate folding of the coupled lines, which partially realize the required compensating elements. The proposed circuit has been theoretically and experimentally verified. The measurement results show a good agreement with both circuit and electromagnetic analysis and prove the correctness and usefulness of the presented method.
Kv1.4 channel block by quinidine: evidence for a drug‐induced allosteric effect

We studied quinidine block of Kv1. 4ΔN, a K+ channel lacking N‐type inactivation, expressed in Xenopus ooctyes. Initially, quinidine intracellularly blocked the open channel so rapidly it overlapped with activation. This rapid open channel block was reduced (non‐additively) by interventions that slow C‐type inactivation: [K+]o elevation and an extracellular lysine to tyrosine mutation (K532Y). These manipulations reduced the affinity of rapid open channel block ≈10‐fold, but left the effective electrical distance unchanged at ≈0.15. Following rapid open channel block, there were time‐dependent quinidine effects: the rate of inactivation during a single depolarisation was increased, and repetitive pulsing showed use dependence. The rate of recovery from the time‐dependent aspect of quinidine block was similar to recovery from normal C‐type inactivation. Manipulations that prevented the channel from entering the C‐type inactivated state (i.e. high [K+]o or the K532Y mutation) prevented the development of the time‐dependent quinidine‐induced inactivation. The concentration dependence of the rapid block and the time‐dependent quinidine‐induced inactivation were similar, but the time‐dependent component was strongly voltage sensitive, with an effective electrical distance of 2. Clearly, this cannot reflect the permeation of quinidine through the electric field, but must be the result of some other voltage‐sensitive change in the channel. We propose that quinidine promotes the entry of the channel into a C‐type inactivated state in a time‐ and voltage‐dependent manner. We developed a mathematical model based on these results to test the hypothesis that, following rapid open channel block, quinidine promotes development of the C‐type inactivated state through a voltage‐dependent conformational change.
Tail muscle parvalbumin content is decreased in chronic sacral spinal cord injured rats with spasticity

In rats, chronic sacral spinal isolation eliminates both descending and afferent inputs to motoneurons supplying the segmental tail muscles, eliminating daily tail muscle EMG activity. In contrast, chronic sacral spinal cord transection preserves afferent inputs, causing tail muscle spasticity that generates quantitatively normal daily EMG. Compared with normal rats, rats with spinal isolation and transection/spasticity provide a chronic model of progressive neuromuscular injury. Using normal, spinal isolated and spastic rats, we characterized the activity dependence of calcium‐handling protein expression for parvalbumin, fast sarco(endo)plasmic reticulum Ca2+‐ATPase (SERCA1) and slow SERCA2. As these proteins may influence fatigue resistance, we also assayed the activities of oxidative (citrate synthase; CS) and glycolytic enzymes (glyceraldehyde phosphate dehydrogenase; GAPDH). We hypothesized that, compared with normal rats, chronic isolation would cause decreased parvalbumin, SERCA1 and SERCA2 expression and CS and GAPDH activities. We further hypothesized that chronic spasticity would promote recovery of parvalbumin, SERCA1 and SERCA2 expression and of CS and GAPDH activities. Parvalbumin, SERCA1 and SERCA2 were quantified with Western blotting. Citrate synthase and GAPDH activities were quantified photometrically. Compared with normal rats, spinal isolation caused large decreases in parvalbumin (95%), SERCA1 (70%) and SERCA2 (68%). Compared with spinal isolation, spasticity promoted parvalbumin recovery (ninefold increase) and a SERCA2‐to‐SERCA1 transformation (84% increase in the ratio of SERCA1 to SERCA2). Compared with normal values, CS and GAPDH activities decreased in isolated and spastic muscles. In conclusion, with complete paralysis due to spinal isolation, parvalbumin expression is nearly eliminated, but with muscle spasticity after spinal cord transection, parvalbumin expression partly recovers. Additionally, spasticity after transection causes a slow‐to‐fast SERCA isoform transformation that may be compensatory for decreased parvalbumin content.
The membrane-associated and secreted forms of the respiratory syncytial virus attachment glycoprotein G are synthesized from alternative initiation codons

Respiratory syncytial (RS) virus synthesizes two mature forms of its attachment glycoprotein G: an anchored type II integral membrane form and a smaller form that is secreted into the medium. Here we demonstrate that these two forms are synthesized as distinct primary translation products of a single species of G protein mRNA by initiation at either of two different AUGs. Mutant cDNAs which eliminated one of the other of the two AUG codons near the 5' end of the G gene open reading frame were constructed. Analysis of the proteins synthesized from these cDNAs, either by translation of transcripts in a cell-free system or in cells infected with recombinant vaccinia viruses containing either one of the mutant cDNAs, showed that elimination of either the first or the second of these AUG codons abrogated the synthesis of the membrane-anchored or the secreted form of the protein, respectively. Additionally, two unglycosylated forms of G protein which comigrated with the unglycosylated G proteins expressed by these recombinant viruses were detected in RS virus-infected cells. Since the second AUG encodes a methionine residue that lies near the middle of the signal/anchor domain, initiation at this codon resulted in a protein with a hydrophobic amino terminus. This form of the glycoprotein was efficiently secreted from cells infected with the vaccinia virus recombinant, and the amino-terminal sequence of this protein was identical to that of G protein secreted from RS virus-infected cells. Our results demonstrate that the secreted form of RS virus G protein is produced by initiation at the second AUG codon of the G open reading frame, followed by proteolytic removal of the signal/anchor domain.
A game theory approach to pairwise classification with support vector machines

Support Vector Machines (SVM) for pattern recognition are discriminant binary classifiers. One of the approaches to extend them to multi-class case is pairwise classification. Pairwise comparisons for each pair of classes are combined together to predict the class or to estimate class probabilities. This paper presents a novel approach, which considers the pairwise S VM classification as a decision-making problem and involves game theory methods to solve it. We prove that in such formulation the solution in pure minimax strategies is equivalent to the solution given by standard fuzzy pairwise SVM method. On the other hand, if we use mixed strategies we formulate new linear programming based pairwise SVM method for estimating class probabilities. We evaluate the performance of the proposed method in experiments with several benchmark datasets, including datasets for optical character recognition and multi-class text categorization problems.
Expression of Ribosomal RNA and Protein Genes in Human Embryonic Stem Cells Is Associated With the Activating H3K4me3 Histone Mark

Embryonic stem cells (ESCs) exhibit unrestricted and indefinite, but stringently controlled, proliferation, and can differentiate into any lineage in the body. In the current study, we test the hypothesis that expression of ribosomal RNA (rRNA) and ribosomal protein genes (RPGs) contribute to the ability of hESCs to proliferate indefinitely. Consistent with the accelerated growth rate of hESCs, we find that hESC lines H1 and H9 both exhibit significantly higher levels of rRNA when compared to a panel of normal and cancer human cell lines. Although many RPGs are expressed at levels that comparable to other human cell lines, a few RPGs also exhibit higher expression levels. In situ nuclear run‐on assays reveal that both nucleoli in hESCs actively transcribe nascent rRNA. Employing genome‐wide chromatin immunoprecipitation‐deep sequencing and bioinformatics approaches, we discovered that, RPGs are dominantly marked by the activating H3K4me3 histone mark in the G1, M, and G2 phases of the cell cycle. Interestingly, the rDNA repeats are marked by the activating H3K4me3 only in the M phase, and repressive H3K27me3 histone mark in all three cell cycle phases. Bioinformatics analyses also reveal that Myc, a known regulator of cell growth and proliferation, occupies both the rRNA genes and RPGs. Functionally, down‐regulation of Myc expression by siRNA results in a concomitant decrease in rRNA levels. Together, our results show that expression of rRNA, which is regulated by the Myc pluripotency transcription factor, and of RPGs in hESCs is associated with the activating H3K4me3 modification. J. Cell. Physiol. 231: 2007–2013, 2016. © 2016 Wiley Periodicals, Inc.
Emergence of coalitions in mean field stochastic systems

In this paper we define and investigate coalition formation for the large population dynamic LQG tracking game that was studied in [1], [2]. First, we present a mean field stochastic control algorithm which, when applied by all agents in the system, gives rise to system behaviour where (i) all agents systems are L2 stable, and (ii) the set of controls yields an ε-Nash equilibrium. Then, as the population size tends to infinity, we show that the system with a coalition state converges to a major-minor agent system studied in [3], where in the limit the coalition state acts as a single major agent. We investigate the existence properties of the coalition state, and further discuss the stability of the coalitions in the overall dynamic system with respect to the fraction of the agents in the coalition.
High-Frequency, In Vitro Reversible Switching of Candida lusitaniae Clinical Isolates from Amphotericin B Susceptibility to Resistance

ABSTRACT Recent studies have revealed an increase in the incidence of serious infections caused by non-albicans Candidaspecies. Candida lusitaniae is of special interest because of its sporadic resistance to amphotericin B (AmB). The present in vitro study demonstrated that, unlike other Candidaspecies, C. lusitaniae isolates frequently generated AmB-resistant lineages form previously susceptible colonies. Cells switching from a resistant colony to a susceptible phenotype were also detected after treatment with either UV light, heat shock, or exposure to whole blood, all of which increased the frequency of switching. In some C. lusitaniae lineages, after a cell switched to a resistant phenotype, the resistant phenotype was stable; in other lineages, colonies were composed primarily of AmB-susceptible cells. Although resistant and susceptible lineages were identical in many aspects, their cellular morphologies were dramatically different. Switching mechanisms that involve exposure to antifungals may have an impact on antifungal therapeutic strategies as well as on standardized susceptibility testing of clinical yeast specimens.
Finding new human minisatellite sequences in the vicinity of long CA-rich sequences.

Microsatellites and minisatellites are two classes of tandem repeat sequences differing in their size, mutation processes, and chromosomal distribution. The boundary between the two classes is not defined. We have developed a convenient, hybridization-based human library screening procedure able to detect long CA-rich sequences. Analysis of cosmid clones derived from a chromosome 1 library show that cross-hybridizing sequences tested are imperfect CA-rich sequences, some of them showing a minisatellite organization. All but one of the 13 positive chromosome 1 clones studied are localized in chromosomal bands to which minisatellites have previously been assigned, such as the 1pter cluster. To test the applicability of the procedure to minisatellite detection on a larger scale, we then used a large-insert whole-genome PAC library. Altogether, 22 new minisatellites have been identified in positive PAC and cosmid clones and 20 of them are telomeric. Among the 42 positive PAC clones localized within the human genome by FISH and/or linkage analysis, 25 (60%) are assigned to a terminal band of the karyotype, 4 (9%) are juxtacentromeric, and 13 (31%) are interstitial. The localization of at least two of the interstitial PAC clones corresponds to previously characterized minisatellite-containing regions and/or ancestrally telomeric bands, in agreement with this minisatellite-like distribution. The data obtained are in close agreement with the parallel investigation of human genome sequence data and suggest that long human (CA)s are imperfect CA repeats belonging to the minisatellite class of sequences. This approach provides a new tool to efficiently target genomic clones originating from subtelomeric domains, from which minisatellite sequences can readily be obtained. [The sequence data described in this paper have been submitted to the EMBL data library under accession nos. AJ000377-AJ000383. ]
Role of preoperative chemotherapy in squamous cell carcinoma of esophagus in kashmir, a cancer belt - a pilot study.

BACKGROUND Esophageal carcinoma is the fifth leading gastrointestinal malignancy and is one of the leading causes of cancer related death. Despite improvements in surgical technique over the last few decades, the outcome has been dismal, with overall 5 year survival not exceeding 15%-25%. AIMS AND OBJECTIVES To evaluate the effect of preoperative chemotherapy on resectability, complication rate and overall survival in patients with squamous cell carcinoma esophagus. MATERIALS AND METHODS 50 patients with histologically confirmed squamous cell carcinoma (SCC), with localised or loco-regional disease (stage 4 excluded) were divided into 2 groups. Group A patients were subjected to 2-3 cycles of pre-operative chemotherapy (5FU-CDDP), whereas Group B patients were directly operated on. OBSERVATIONS 3 (12%) patients in group A showed complete pathological response to chemotherapy and 18 (72%) showed a partial response, with four patients (16%) showing resistance to chemotherapy. There was no statistically significant difference in terms of response to chemotherapy with respect to degree of differentiation of tumor. There was no significant difference in the overall resectability rates between the two groups (p > 0.05), but R0 resection was achieved in 20 (80%) of group A and only 10 (40%) of group B, the difference being statistically significant (p < 0.05). The rate of overall complications was also much higher in the control group. Initially there was no significant difference in the survival between the two groups, but later (20 months) the study group showed a slight non-significant advantage. CONCLUSION Preoperative chemotherapy significantly increases the rate of R0 resection without significantly increasing postoperative morbidity and mortality in patients with squamous cell carcinoma of esophagus. However, to assess the impact on survival the study period needs to be extended.
Clinical and economic outcomes of thyroid and parathyroid surgery in children.

CONTEXT Clinical and economic outcomes after thyroidectomy/parathyroidectomy in adults have demonstrated disparities based on patient age and race/ethnicity; there is a paucity of literature on pediatric endocrine outcomes. OBJECTIVE The objective was to examine the clinical and demographic predictors of outcomes after pediatric thyroidectomy/parathyroidectomy. DESIGN This study is a cross-sectional analysis of Healthcare Cost and Utilization Project-National Inpatient Sample hospital discharge information from 1999-2005. All patients who underwent thyroidectomy/parathyroidectomy were included. Bivariate and multivariate analyses were performed to identify independent predictors of patient outcomes. SUBJECTS Subjects included 1199 patients 17 yr old or younger undergoing thyroidectomy/parathyroidectomy. MAIN OUTCOME MEASURES Outcome measures included in-hospital patient complications, length of stay (LOS), and inpatient hospital costs. RESULTS The majority of patients were female (76%), aged 13-17 yr (71%), and White (69%). Whites were more often in the highest income group (80% vs. 8% for Hispanic and 6% for Black; P < 0.01) and had private/HMO insurance (76% vs. 10% for Hispanic and 5% for Black; P < 0.001) rather than Medicaid (13% vs. 32% for Hispanic and 41% for Black; P < 0.001). Ninety-one percent of procedures were thyroidectomies and 9% parathyroidectomies. Children aged 0-6 yr had higher complication rates (22% vs. 15% for 7-12 yr and 11% for 13-17 yr; P < 0.01), LOS (3.3 d vs. 2.3 for 7-12 yr and 1.8 for 13-17 yr; P < 0.01), and higher costs. Compared with children from higher-income families, those from lower-income families had higher complication rates (11.5 vs. 7.7%; P < 0.05), longer LOS (2.7 vs. 1.7 d; P < 0.01), and higher costs. Children had higher endocrine-specific complication rates than adults after parathyroidectomy (15.2 vs. 6.2%; P < 0.01) and thyroidectomy (9.1 vs. 6.3%; P < 0.01). CONCLUSIONS Children undergoing thyroidectomy/parathyroidectomy have higher complication rates than adult patients. Outcomes were optimized when surgeries were performed by high-volume surgeons. There appears to be disparity in access to high-volume surgeons for children from low-income families, Blacks, and Hispanics.
Mannan Chain Length Controls Lipoglycans Signaling via and Binding to TLR21

TLR2 is a pattern-recognition receptor that is activated by a large variety of conserved microbial components, including lipoproteins, lipoteichoic acids, and peptidoglycan. Lipoglycans are TLR2 agonists found in some genera of the phylogenetic order Actinomycetales, including Mycobacterium. They are built from a mannosyl-phosphatidyl-myo-inositol anchor attached to a (α1→6)-linked d-mannopyranosyl chain whose units can be substituted by d-mannopyranosyl and/or d-arabinofuranosyl units. At this time, little is known about the molecular bases underlying their ability to induce signaling via this receptor. We have recently shown that the anchor must be at least triacylated, including a diacylglyceryl moiety, whereas the contribution of the glycosidic moiety is not yet clearly defined. We show herein that lipoglycan activity is directly determined by mannan chain length. Indeed, activity increases with the number of units constituting the (α1→6)-mannopyranosyl backbone but is also critically dependent on the substitution type of the 2-hydroxyl of these units. We thus provide evidence for the definition of a new pattern that includes the nonlipidic moiety of the molecules, most probably as a result of the (α1→6)-mannopyranosyl backbone being a highly conserved structural feature among lipoglycans. Moreover, we demonstrate that lipoglycans can bind cell surface-expressed TLR2 and that their ability to induce signaling might be, at least in part, dictated by their avidity for the receptor. Finally, our data suggest that lipoglycans and lipoproteins have a common binding site. The present results are thus discussed in the light of the recently published crystal structure of a TLR1-TLR2-lipopeptide complex.
Proteome Profiling without Selection Bias

In this paper, we present a method for predictive profiling of mass spectrometry data. The method integrates a spectra preprocessing pipeline with a complete validation setup aimed at identifying the discriminating peaks and at providing an unbiased estimate of the predictive classification error, based on SVM classifiers and on entropy-based RFE procedure. A particular emphasis is placed upon avoiding selection bias effects throughout all the analysis steps, from preprocessing to peak importance ranking