Miracle-dz/UniFAR-FTUs huggingface dataset:
Decreased susceptibility to Fas-induced apoptosis of systemic sclerosis dermal fibroblasts.

OBJECTIVE To determine whether dysregulated apoptosis of systemic sclerosis (SSc) fibroblasts contributes to progressive fibrosis by promoting fibroblast longevity. METHODS We examined the pattern of fibroblast proliferation and apoptosis in SSc skin lesions and the susceptibility of cultured SSc dermal fibroblasts to apoptosis. Skin biopsy samples from SSc patients and control subjects were used to establish fibroblast cultures and were examined histologically. In skin sections, apoptosis was examined by TUNEL, and proliferation by immunostaining for proliferating cell nuclear antigen. Susceptibility of fibroblasts to apoptosis induced in vitro by different stimuli was studied by TUNEL. Expression of Bcl-2, Bcl-x, and Bax proteins in cultured fibroblasts was studied by Western blotting. RESULTS Proliferation of dermal fibroblasts was not observed in normal skin but was present in skin from patients with SSc and other inflammatory skin diseases. Apoptosis of fibroblasts in SSc fibrotic skin lesions was not observed. In vitro, SSc fibroblasts were specifically resistant to apoptosis induced by Fas receptor stimulation but had normal susceptibility to apoptosis induced by nonspecific stimuli (protein kinase inhibition or serum withdrawal). Decreased susceptibility to Fas stimulation was not caused by decreased levels of surface Fas receptor. In SSc fibroblasts, quiescence induced by confluence and serum starvation was followed by an abnormal down-regulation of proapoptotic Bax protein. Up-regulation of the Bax:Bcl-2 ratio in SSc fibroblasts by Bcl-2 antisense oligonucleotides restored their susceptibility to Fas-mediated apoptosis. CONCLUSION Our findings suggest that abnormal apoptotic regulation in fibroblasts can contribute to the pathogenesis of progressive fibrosis in SSc. Modulation of Bcl-2-related proteins appears to be a potential target for the development of apoptosis-based antifibrotic strategies.
Computational modeling of online reaching

Humans are able to perform an unlimited repertoire of reaching movements with high accuracy. The skillfulness with which we carry out a giving reaching task suggests that there are fundamental control policies that allow us to move our body. In the current paper we examine how an adaptive reach policy can be established, using biologically inspired techniques. The developed model, after an initial imitation phase, can replicate any given trajectory with very good performance.
TRUSS, a Novel Tumor Necrosis Factor Receptor 1 Scaffolding Protein That Mediates Activation of the Transcription Factor NF-κB

ABSTRACT We describe the cloning and characterization of tumor necrosis factor receptor (TNF-R)-associated ubiquitous scaffolding and signaling protein (TRUSS), a novel TNF-R1-interacting protein of 90.7 kDa. TRUSS mRNA was ubiquitously expressed in mouse tissues but was enriched in heart, liver, and testis. Coimmunoprecipitation experiments showed that TRUSS was constitutively associated with unligated TNF-R1 and that the complex was relatively insensitive to stimulation with TNF-α. Deletion mutagenesis of TNF-R1 indicated that TRUSS interacts with both the membrane-proximal region and the death domain of TNF-R1. In addition, the N-terminal region of TRUSS (residues 1 to 440) contains sequences that permit association with the cytoplasmic domain of TNF-R1. Transient overexpression of TRUSS activated NF-κB and increased NF-κB activation in response to ligation of TNF-R1. In contrast, a COOH-terminal-deletion mutant of TRUSS (TRUSS1-723) was found to inhibit NF-κB activation by TNF-α. Coprecipitation and coimmunoprecipitation assays revealed that TRUSS can interact with TRADD, TRAF2, and components of the IKK complex. These findings suggest that TRUSS may serve as a scaffolding protein that interacts with TNF-R1 signaling proteins and may link TNF-R1 to the activation of IKK.
Improving cancer screening among lesbians over 50: results of a pilot study.

PURPOSE/OBJECTIVES To explore the impact of two one-hour lesbian-specific educational interventions by a lesbian physician on the cancer screening behaviors of lesbians. DESIGN A pilot pre- and post-test intervention study. SETTING Two lesbian, gay, bisexual, and transgendered senior organizations in the San Francisco Bay Area (one urban, one suburban). SAMPLE 36 participants aged 50-81 (meanX = 60.2, SD = 6.48). The majority were Caucasian (86%), single (61%), living in urban areas (67%), employed (56%), and educated beyond high school (meanX = 15.47 years, SD = 2.90, range 9-21). Eleven percent (n = 4) did not have any health insurance and were not on Medicaid or Medicare. METHODS A lesbian physician led a one-hour, didactic, lesbian- specific educational program on cancer screening, including a review of current research findings with regard to lesbians' risk for cancer and 45 minutes of information on recommended cancer screening, followed by a 15-minute question-and-answer period. Participants completed a pre- and postintervention survey. FINDINGS Follow-up data were available for 22 women. Of the six women (27%) who had not focused their attention on breast screening behaviors for two years or more, one-third had obtained mammograms and half began performing monthly breast self-examinations. Of the four women (18%) who had not undergone a pelvic examination for three years or more, one obtained a pelvic examination. The women reported no changes in colorectal cancer screening behaviors. CONCLUSIONS Some of these difficult-to-reach women changed their behavior in a very short period of time, supporting the need for a larger study to confirm these findings. IMPLICATIONS FOR NURSING A need exists to develop appropriate interventions for the underserved population of lesbians older than 50.
Efficient ticket routing by resolution sequence mining

IT problem management calls for quick identification of resolvers to reported problems. The efficiency of this process highly depends on ticket routing---transferring problem ticket among various expert groups in search of the right resolver to the ticket. To achieve efficient ticket routing, wise decision needs to be made at each step of ticket transfer to determine which expert group is likely to be, or to lead to the resolver. In this paper, we address the possibility of improving ticket routing efficiency by mining ticket resolution sequences alone, without accessing ticket content. To demonstrate this possibility, a Markov model is developed to statistically capture the right decisions that have been made toward problem resolution, where the order of the Markov model is carefully chosen according to the conditional entropy obtained from ticket data. We also design a search algorithm, called Variable-order Multiple active State search(VMS), that generates ticket transfer recommendations based on our model. The proposed framework is evaluated on a large set of real-world problem tickets. The results demonstrate that VMS significantly improves human decisions: Problem resolvers can often be identified with fewer ticket transfers.
Frequency of KRAS, BRAF, and NRAS mutations in colorectal cancer

Mutational analysis of KRAS codons 12 and 13 is standard for patients with metastatic colorectal cancer since mutations in these codons predict lack of response to anti‐EGFR therapies. However, even among patients whose tumors are wildtype for KRAS codons 12 and 13, only a subset respond to therapy. Since additional activating mutations downstream of EGFR may also play a role in treatment resistance, we sought to establish the frequency of these mutations. We evaluated 2121 colorectal tumors for mutations in codons 12 and 13 of the KRAS gene. A subset of these samples, comprised of 513 samples wildtype for KRAS codons 12 and 13, were tested for mutations in codons 61 and 146 of KRAS, codon 600 of BRAF, and codons 12, 13, and 61 of NRAS. Mutation status was determined by targeted pyrosequencing. Mutations in KRAS codon 12 or 13 were identified in 900/2121 (42.4%) samples. Of the 513 wildtype samples tested for additional mutations, 78 samples were mutant for BRAF, 19 for KRAS codon 61, 17 for KRAS codon 146, and 26 for NRAS. In total, 140/513 (27.3%) tumors wildtype for KRAS codons 12 and 13 harbored a mutation in another of the RAS pathway genes. While further study is needed to determine the full therapeutic implications of mutations in these codons, mutational testing of these codons may be useful for identifying a significant proportion of patients who may also be resistant to anti‐EGFR therapies. © 2011 Wiley‐Liss, Inc.
Blood Compatibility of Novel Zwitterionic PEG-Grafted Nitinol Alloy for Peripheral Arterial Stents

In this study, newly synthesized zwitterionic PEG was grafted on Nitinol alloy using oxidation treatment. The surface property and blood compatibility of surface-modified Nitinols were examined. The results of surface analysis showed that the contact angle and the ratio of oxygen to carbon significantly decreased with Nitinol alloys. The total amount of fibrinogen (0.095 μg/cm2) adsorbed onto TiNi-PEG2K-N+-S- was lower than that of TiNi control (0.12 μg/cm2). The platelet adhesion decreased in the order of TiNi control > TiNi-MPEG2K > TiNi-PEG2K-N+-S. Particularly, zwitterionic PEG with PEG2K was proven better than any others. The results indicated that zwitterionic PEG surface could significantly suppress platelet adhesion and protein adsorption as compared to other samples. The present study suggested that grafted zwitterionic PEG structure may possess improved blood compatibility.
Mechanisms of silver nanoparticle-induced toxicity and important role of autophagy

Abstract Safety concerns have been raised over the extensive applications of silver nanoparticles (AgNPs) because nano dimensions make them highly bioactive, being potentially harmful to the exposed humans. Surface physico-chemistry (shape, surface charge, chemical composition, etc.) that mainly dictates nano-bio interactions is relevant for influencing their biocompatibility and toxicity. Although the hazardousness of AgNPs has been demonstrated in vitro and in vivo, mechanistic understanding of the toxicity particularly at the molecular and organismal levels, in addition to oxidative stress and silver ion dissolution, has remained unclear. A growing body of research has elucidated that autophagy, being activated in response to exposure to various nanomaterials, may serve as a cellular defense mechanism against nanotoxicity. Recently, autophagy activation was shown to correlate with AgNPs exposure; however, the subsequent autophagosome–lysosome fusion was defective. As autophagy plays a crucial role in selective removal of stress-mediated protein aggregates and injured organelles, AgNPs-induced autophagic flux defect may consequently lead to aggravated cytotoxic responses. Furthermore, we suggest that p62 accumulation resulting from defective autophagy may also potentially account for AgNPs cytotoxicity. Intriguingly, AgNPs have been shown to interfere with ubiquitin modifications, either via upregulating levels of enzymes participating in ubiquitination, or through impairing the biological reactivity of ubiquitin (due to formation of AgNPs-ubiquitin corona). Ubiquitination both confers selectivity to autophagy as well as modulates stabilization, activation, and trafficking of proteins involved in autophagic clearance pathways. In this regard, we offer a new perspective that interference of AgNPs with ubiquitination may account for AgNPs-induced defective autophagy and cytotoxic effects.
The 1.7 A crystal structure of BPI: a study of how two dissimilar amino acid sequences can adopt the same fold.

We have extended the resolution of the crystal structure of human bactericidal/permeability-increasing protein (BPI) to 1.7 A. BPI has two domains with the same fold, but with little sequence similarity. To understand the similarity in structure of the two domains, we compare the corresponding residue positions in the two domains by the method of 3D-1D profiles. A 3D-1D profile is a string formed by assigning each position in the 3D structure to one of 18 environment classes. The environment classes are defined by the local secondary structure, the area of the residue which is buried from solvent, and the fraction of the area buried by polar atoms. A structural alignment between the two BPI domains was used to compare the 3D-1D environments of structurally equivalent positions. Greater than 31% of the aligned positions have conserved 3D-1D environments, but only 13% have conserved residue identities. Analysis of the 3D-1D environmentally conserved positions helps to identify pairs of residues likely to be important in conserving the fold, regardless of the residue similarity. We find examples of 3D-1D environmentally conserved positions with dissimilar residues which nevertheless play similar structural roles. To generalize our findings, we analyzed four other proteins with similar structures yet dissimilar sequences. Together, these examples show that aligned pairs of dissimilar residues often share similar structural roles, stabilizing dissimilar sequences in the same fold.
Fiber-optic sensor for detection of hydrogen peroxide in PEM fuel cells

Supervisory Committee Dr. Nedjib Djilali, Department of Mechanical Engineering Co-supervisor Dr. Peter Wild, Department of Mechanical Engineering Co-supervisor Dr. Alexandre G. Brolo, Department of Chemistry Outside Member This dissertation presents chemical sensors that are based on an emerging optical fiber sensing technology for the determination of the presence and concentration of hydrogen peroxide (H2O2) at low concentrations. The motivation to determine hydrogen peroxide lies on the fact that this chemical species is generated as a by-product of the operation of hydrogen-based polymer electrolyte membrane fuel cells (PEMFCs), and the presence and formation of this peroxide has been associated with the chemical degradation that results in low durability of PEMFCs. Currently, there are no techniques that allow the hydrogen peroxide to be determined in situ in PEMFCs in a reliable manner, since the only report of this type of measurement was performed using electrochemical techniques, which can be affected by the environmental conditions and that can alter the proper operation of the PEMFCs. The sensors presented in this dissertation are designed to detect the presence and quantify hydrogen peroxide in solution at the conditions at which PEMFCs operate. Since they are made using fused silica optical fibers and are based on a spectroscopic technique to perform the detection of H2O2, they are not affected by the electromagnetic fields or the harsh chemical environment inside PEMFCs. In addition, they are able to still detect the presence of H2O2 at the operating temperatures. iv The construction of the sensing film on the tip of an optical fiber and its small size (125 μm diameter), make the sensors here developed an ideal solution for being deployed in situ in PEMFCs, ensuring that they would be minimally invasive and that the operation of the fuel cell would not be compromised by the presence of the sensor. The sensors developed in this dissertation not only present design characteristics that are applicable to PEMFCs, they are also suitable for applications in other fields such as environmental, defense, and biological processes.
Association of pericardial fat, intrathoracic fat, and visceral abdominal fat with cardiovascular disease burden: the Framingham Heart Study.

AIMS The aim of this study was to assess whether pericardial fat, intrathoracic fat, and visceral abdominal adipose tissue (VAT) are associated with the prevalence of cardiovascular disease (CVD). METHODS AND RESULTS Participants from the Framingham Heart Study Offspring cohort underwent abdominal and chest multidetector computed tomography to quantify volumes of pericardial fat, intrathoracic fat, and VAT. Relations between each fat depot and CVD were assessed using logistic regression. The analysis of 1267 participants (mean age 60 years, 53.8% women, 9.7% with prevalent CVD) demonstrated that pericardial fat [odds ratio (OR) 1.32, 95% confidence interval (CI) 1.11-1.57; P = 0.002] and VAT (OR 1.35, 95% CI 1.11-1.57; P = 0.003), but not intrathoracic fat (OR 1.14, 95% CI 0.93-1.39; P = 0.22), were significantly associated with prevalent CVD in age-sex-adjusted models and after adjustment for body mass index and waist circumference. After multivariable adjustment, associations were attenuated (P > 0.14). Only pericardial fat was associated with prevalent myocardial infarction after adjusting for conventional measures of adiposity (OR 1.37, 95% CI 1.03-1.82; P = 0.03). CONCLUSION Pericardial fat and VAT, but not intrathoracic fat, are associated with CVD independent of traditional measures of obesity but not after further adjustment for traditional risk factor. Taken together with our prior work, these findings may support the hypothesis that pericardial fat contributes to coronary atherosclerosis.
Possible role of non-classical chromatophorotropins on the regulation of the crustacean erythrophore.

Two neuropeptides, the pigment dispersing hormone (PDH) and the pigment concentrating hormone (PCH), are well known to respectively promote centrifugal and centripetal granule translocation in the freshwater shrimp Macrobrachium potiuna erythrophores. Herein, we demonstrate for the first time the effects of crustacean non-classical chromatophorotropins on the pigment migration in M. potiuna erythrophores. Although proctolin, 20-hydroxyecdisone (20HE), and melatonin were ineffective, the crustacean cardioactive peptide (CCAP) was a full agonist, inducing pigment dispersion in a dose-dependent manner with EC(50) of 9.5. 10(-7) M. In addition, concentrations of CCAP lower than the minimal effective dose (10(-8) and 10(-7) M) decreased the PCH-induced aggregation, shifting rightward the dose-response curve (DRC) to PCH 2.2- and 29-fold, respectively. Surprisingly, melatonin (10(-7) and 10(-6) M) also shifted to the right 8.7- and 46.5-fold, respectively, the DRC to PCH. In conclusion, our data demonstrate that besides PCH and PDH, CCAP and melatonin also regulate the pigment migration within the crustacean erythrophore. J. Exp. Zool. 284:711-716, 1999.
Apprentissage d'inférences par édition d'arbres pour répondre à des questions

In order to answer question, we propose a matching algorithm that consists in generating and learning inferences needed to rely text passages to pairs (question, candidate answer). We first retrieve relevant passages, through lexical expansion involving WordNet and word vectors, that are enriches by lexico-semantic resources. Then a tree edit model is used on graph representations of the passages and answer choices to extract edit sequences. Finally, features are computed from those edit sequences and used in two machine-learned models, one for validating answers and one for invalidating answers, in order to take the final decision. This method was evaluated in the Entrance Exams task at QALD@CLEF, that consists in answering QCMs on given texts, yielding the second best precision score on the task.
More than two decades of research on insect neuropeptide GPCRs: an overview

This review focuses on the state of the art on neuropeptide receptors in insects. Most of these receptors are G protein-coupled receptors (GPCRs) and are involved in the regulation of virtually all physiological processes during an insect's life. More than 20 years ago a milestone in invertebrate endocrinology was achieved with the characterization of the first insect neuropeptide receptor, i.e., the Drosophila tachykinin-like receptor. However, it took until the release of the Drosophila genome in 2000 that research on neuropeptide receptors boosted. In the last decade a plethora of genomic information of other insect species also became available, leading to a better insight in the functions and evolution of the neuropeptide signaling systems and their intracellular pathways. It became clear that some of these systems are conserved among all insect species, indicating that they fulfill crucial roles in their physiological processes. Meanwhile, other signaling systems seem to be lost in several insect orders or species, suggesting that their actions were superfluous in those insects, or that other neuropeptides have taken over their functions. It is striking that the deorphanization of neuropeptide GPCRs gets much attention, but the subsequent unraveling of the intracellular pathways they elicit, or their physiological functions are often hardly examined. Especially in insects besides Drosophila this information is scarce if not absent. And although great progress made in characterizing neuropeptide signaling systems, even in Drosophila several predicted neuropeptide receptors remain orphan, awaiting for their endogenous ligand to be determined. The present review gives a précis of the insect neuropeptide receptor research of the last two decades. But it has to be emphasized that the work done so far is only the tip of the iceberg and our comprehensive understanding of these important signaling systems will still increase substantially in the coming years.
Exploiting process lifetime distributions for dynamic load balancing

We measure the distribution of lifetimes for UNIX processes and propose a functional form that fits this distribution well. We use this functional form to derive a policy for preemptive migration, and then use a trace-driven simulator to compare our proposed policy with other preemptive migration policies, and with a non-preemptive load balancing strategy. We find that, contrary to previous reports, the performance benefits of preemptive migration are significantly greater than those of non-preemptive migration, even when the memory-transfer cost is high. Using a model of migration costs representative of current systems, we find that preemptive migration reduces the mean delay (queueing and migration) by 35 - 50%, compared to non-preemptive migration.
A New Channel Quantization Strategy for MIMO Interference Alignment with Limited Feedback

In K-user multiple-input multiple-output (MIMO) interference channels, it was shown that interference alignment (IA) achieves a full spatial multiplexing gain when perfect channel state information (CSI) is available at each transmitter in the network. When the CSI is fed back from receivers using the limited number of feedback bits, a significant performance loss is inevitable in the IA due to quantized channel knowledge. In this paper, we propose a new channel quantization strategy to optimize the performance of the IA with limited feedback. In our proposed scheme, we introduce an additional receive filter to minimize the chordal distance which accounts for the quantization error on Grassmann manifold. Besides, we analyze a reduction in terms of the chordal distance in our scheme compared to conventional methods. Simulation results verify that the proposed scheme provides substantially better performance than the conventional method as the number of feedback bits is increased. We show that our scheme exhibits 30% and 40% sum rate gains compared to the conventional scheme when the numbers of the feedback bits are 10 and 15, respectively, with two antennas per node.