Miracle-dz/UniFAR-FTUs huggingface dataset:
Type I Interferons in the Treatment of Pancreatic Cancer: Mechanisms of Action and Role of Related Receptors

Objective:We evaluated the role of type I interferons (IFNs) and IFN receptors in the regulation of cell growth in 3 human pancreatic adenocarcinoma cell lines (BxPC-3, MiaPaCa-2, and Panc-1). Background:Chemotherapy and radiotherapy have a marginal role in the management of pancreatic adenocarcinoma. The addition of IFN-α showed promising results in early clinical trials. Methods:Cell proliferation and apoptosis were evaluated by DNA measurement and DNA fragmentation, respectively. Type I IFN receptor (IFNAR-1 and IFNAR-2 subunits) was determined by quantitative RT-PCR and immunocytochemistry. Cell cycle distribution was evaluated by propidium iodide staining and flow-cytometric analysis. Results:The incubation with IFN-β for 6 days showed a potent inhibitory effect on the proliferation of BxPC-3 (IC50, 14 IU/mL) and MiaPaCa-2 (IC50, 64 IU/mL). The inhibitory effect of IFN-β was stronger than IFN-α in all 3 cell lines and mainly modulated by the stimulation of apoptosis, although cell cycle arrest was induced as well. The expression of the type I IFN receptors was significantly higher in BxPC-3 (the most sensitive cell line to IFN) and mainly localized on the membrane, whereas in Panc-1 (the most resistant cell line) about 60% to 70% of cells were negative for IFNAR-2c with a mainly cytoplasmic staining for IFNAR-2c. Conclusion:The antitumor activity of IFN-β is more potent than IFN-α in pancreatic cancer cell lines through the induction of apoptosis. Further studies should investigate in vivo whether the intensity and distribution of IFNAR-1 and IFNAR-2c may predict the response to therapy with IFN-α and IFN-β in pancreatic cancer.
Survival of Neural Stem Cell Grafts in the Lesioned Spinal Cord Is Enhanced by a Combination of Treadmill Locomotor Training via Insulin-Like Growth Factor-1 Signaling

Combining cell transplantation with activity-based rehabilitation is a promising therapeutic approach for spinal cord repair. The present study was designed to investigate potential interactions between the transplantation (TP) of neural stem cells (NSCs) obtained at embryonic day 14 and treadmill training (TMT) in promoting locomotor recovery and structural repair in rat contusive injury model. Combination of TMT with NSC TP at 1 week after injury synergistically improved locomotor function. We report here that combining TMT increased the survival of grafted NSCs by >3-fold and >5-fold at 3 and 9 weeks after injury, respectively. The number of surviving NSCs was significantly correlated with the extent of locomotor recovery. NSCs grafted into the injured spinal cord were under cellular stresses induced by reactive nitrogen or oxygen species, which were markedly attenuated by TMT. TMT increased the concentration of insulin-like growth factor-1 (IGF-1) in the CSF. Intrathecal infusion of neutralizing IGF-1 antibodies, but not antibodies against either BDNF or Neurotrophin-3 (NT-3), abolished the enhanced survival of NSC grafts by TMT. The combination of TP and TMT also resulted in tissue sparing, increased myelination, and restoration of serotonergic fiber innervation to the lumbar spinal cord to a larger extent than that induced by either TP or TMT alone. Therefore, we have discovered unanticipated beneficial effects of TMT in modulating the survival of grafted NSCs via IGF-1. Our study identifies a novel neurobiological basis for complementing NSC-based spinal cord repair with activity-based neurorehabilitative approaches.
Identification of Murine Poxvirus-Specific CD8+ CTL Epitopes with Distinct Functional Profiles1

Murine T cell epitopes against vaccinia virus (VV) have not been characterized to date in part due to the large and complex genome of VV. We have identified and characterized two CD8+ T cell epitopes on the A47L (modified VV Ankara strain (MVA)-029) and J6R (MVA-043) proteins of VV that are Db and Kb restricted, respectively. Following i.p. immunization with VV New York City Board of Health (NYCBH) strain, MVA-029 peptide-stimulated splenocytes secreted IFN-γ from 7 days to 7 mo postimmunization, and virus-stimulated effectors were also able to lyse MVA-029-pulsed target cells at the same time points. In contrast, MVA-043 peptide-stimulated splenocytes secreted very low levels of IFN-γ only at day 7 but maintained the ability to lyse target cells up to 2 mo postimmunization. Both MVA-029 and MVA-043 peptide-stimulated lymph node cells degranulated similarly as assessed by Ag-induced CD107 expression. T cell responses to whole-virus stimulation remained robust and steady during the acute and memory T cell response to VV. Identification of T cell epitopes on VV will enable further studies to increase our understanding of the role of CD8+ T cells in VV infection and assist in the design of new protective strategies.
[Laypersons can seek help from their Facebook friends regarding medical diagnosis].

INTRODUCTION In contrast to Internet search engines, social media on the Internet such as Facebook, Twitter, etc. reach a large number of people, who are ready to help answering questions. This type of information aggregation has been dubbed "crowdsourcing" i.e. outsourcing a task to a large group of people or community (a crowd) through an open call. Our aim was to explore whether laypersons via Facebook friends could crowd source their way to a medical diagnosis based on a brief medical history, posted as a status update on Facebook. MATERIAL AND METHODS The participants posted a brief case story on their Facebook profile and asked their "Facebook friends" to come up with possible diagnoses. RESULTS The correct diagnosis was suggested in five of the six case stories, and the correct diagnosis was made after a median of ten minutes. The quality of the responses varied from relevant differential diagnoses to very silly diagnostic suggestions. CONCLUSION Based on this study, we believe that laypersons can use his or her "Facebook friends" to identify the need to see a doctor for their symptoms rather than relying on them to give them a specific diagnosis for their symptoms.
Transcriptional Polarity in rRNA Operons of Escherichia coli nusA and nusB Mutant Strains

ABSTRACT Synthesis of ribosomes in Escherichia coli requires an antitermination system that modifies RNA polymerase to achieve efficient transcription of the genes specifying 16S, 23S, and 5S rRNA. This modification requires nucleotide signals in the RNA and specific transcription factors, such as NusA and NusB. Transcription of rrn operons in strains lacking the ability to produce either NusA or NusB was examined by electron microscopy. The distribution and numbers of RNA polymerase molecules on rrn operons were determined for each mutant. Compared to the wild type, the 16S gene in the nusB mutant strain had an equivalent number of RNA polymerase molecules, but the number of RNA polymerase molecules was reduced 1.4-fold for the nusA mutant. For both mutant strains, there were twofold-fewer RNA polymerase molecules on the 23S RNA gene than for the wild type. Overall, the mutant strains each had 1.6-fold-fewer RNA polymerase molecules on their rrn operons than did the wild type. To determine if decreased transcription of the 23S gene observed by electron microscopy also affected the 30S/50S ribosomal subunit ratio, ribosome profiles were examined by sucrose gradient analysis. The 30S/50S ratio increased 2.5- to 3-fold for the nus mutant strains over that for wild-type cells. Thus, strains carrying either a nusA mutation or a nusB mutation have defects in transcription of 23S rRNA.
Recent advances in the MS analysis of glycoproteins: Theoretical considerations

Protein glycosylation is involved in a broad range of biological processes that regulate protein function and control cell fate. As aberrant glycosylation has been found to be implicated in numerous diseases, the study and large‐scale characterization of protein glycosylation is of great interest not only to the biological and biomedical research community, but also to the pharmaceutical and biotechnology industry. Due to the complex chemical structure and differing chemical properties of the protein/peptide and glycan moieties, the analysis and structural characterization of glycoproteins has been proven to be a difficult task. Large‐scale endeavors have been further limited by the dynamic outcome of the glycosylation process itself, and, occasionally, by the low abundance of glycoproteins in biological samples. Recent advances in MS instrumentation and progress in miniaturized technologies for sample handling, enrichment and separation, have resulted in robust and compelling analysis strategies that effectively address the challenges of the glycoproteome. This review summarizes the key steps that are involved in the development of efficient glycoproteomic analysis methods, and the latest innovations that led to successful strategies for the characterization of glycoproteins and their corresponding glycans. As a follow‐up to this work, we review innovative capillary and microfluidic‐MS workflows for the identification, sequencing and characterization of glycoconjugates.
Forward Rate Volatilities, Swap Rate Volatilities, and Implementation of the LIBOR Market Model

This article presents a number of new ideas concerned with implementation of the LIBOR market model and its extensions. It develops and tests an analytic approximation for calculating the volatilities the market uses to price European swap options from the volatilities used to price interest rate caps. The approximation is very accurate for the range of market parameters normally encountered, and enables swap option volatility skews to be implied from cap volatility skews. It also allows the LIBOR market model to be calibrated to broker quotes on caps and European swap options so that other interest rate derivatives can be valued.
Tax-Benefits Reforms and the Labor Market: Evidence from Belgium and Other EU Countries

During the last decade, several EU countries have tried to tackle unemployment and low activity rates through extensive tax cuts. In an efiort to encourage the taking up of work - especially amongst the less productive workers - policymakers have shown increasing interest in targeted tax and social security contribution rebates as well as in beneflts conditional on being in employment. This paper surveys recent tax-beneflt reforms in Germany, the Netherlands, Italy, The UK, France and Belgium, focussing in particular on the reforms carried out in the latter. The potential labor supply efiect of the Belgian reforms are assessed via a discrete hours labor supply model. The results are then compared to similar evaluations of reforms implemented in the aforementioned countries. Results suggest that: (i) generalized tax cut are not always efiective in stimulating labor supply; (ii) in several central continental Europe, social security contributions play a major role in determining the incentives to take up work; (iii) joint assessment of income for both purposes of taxation and beneflt eligibility has unambiguous negative efiects on the labor supply of secondary earners (i.e. mostly women); (iv) targeted reductions in taxes and social security contributions, as well as beneflts conditioned on employment are efiective means to promote employment, but (v) e‐cient design of these policies is of greatest importance in order to counter potential negative incentive efiects on the population already in employment.
Comparison of Clinical Efficacy between a Single Administration of Long-Acting Gonadotrophin-Releasing Hormone Agonist (GnRHa) and Daily Administrations of Short-Acting GnRHa in In Vitro Fertilization-Embryo Transfer Cycles

This study was aimed to evaluate the efficacy of a single administration of long-acting gonadotrophin-releasing hormone agonist (GnRHa) as compared with daily administrations of short-acting GnRHa in controlled ovarian hyperstimulation (COH) for in vitro fertilization and embryo transfer (IVF-ET) cycles. The mean dosage of recombinant follicle-stimulating hormone (rFSH) required for COH (2,354.5±244.2 vs. 2,012.5±626.1 IU) and the rFSH dosage per retrieved oocyte (336.7±230.4 vs. 292.1±540.4 IU) were significantly higher in the long-acting GnRHa group (N=22) than those in the short-acting GnRHa group (N=28) (p<0.05). However, the mean number of visit to the hospital that was required before ovum pick-up (3.3±0.5 vs. 22.2±2.0) and the frequency of injecting GnRHa and rFSH (12.8±1.2 vs. 33.5±3.5) were significantly decreased in the long-acting GnRHa group (p<0.0001). The clinical pregnancy rate, implantation rate, and early pregnancy loss rate were not significantly different between the 2 groups. So, we suggest that a single administration of long-acting GnRHa is a useful alternative for improving patient's convenience with clinical outcomes comparable to daily administrations of short-acting GnRHa in COH for IVF-ET cycles.
Interaural Time Difference Processing in the Mammalian Medial Superior Olive: The Role of Glycinergic Inhibition

The dominant cue for localization of low-frequency sounds are microsecond differences in the time-of-arrival of sounds at the two ears [interaural time difference (ITD)]. In mammals, ITD sensitivity is established in the medial superior olive (MSO) by coincidence detection of excitatory inputs from both ears. Hence the relative delay of the binaural inputs is crucial for adjusting ITD sensitivity in MSO cells. How these delays are constructed is, however, still unknown. Specifically, the question of whether inhibitory inputs are involved in timing the net excitation in MSO cells, and if so how, is controversial. These inhibitory inputs derive from the nuclei of the trapezoid body, which have physiological and structural specializations for high-fidelity temporal transmission, raising the possibility that well timed inhibition is involved in tuning ITD sensitivity. Here, we present physiological and pharmacological data from in vivo extracellular MSO recordings in anesthetized gerbils. Reversible blockade of synaptic inhibition by iontophoretic application of the glycine antagonist strychnine increased firing rates and significantly shifted ITD sensitivity of MSO neurons. This indicates that glycinergic inhibition plays a major role in tuning the delays of binaural excitation. We also tonically applied glycine, which lowered firing rates but also shifted ITD sensitivity in a way analogous to strychnine. Hence tonic glycine application experimentally decoupled the effect of inhibition from the timing of its inputs. We conclude that, for proper ITD processing, not only is inhibition necessary, but it must also be precisely timed.
Instructions for use Title Haplotypes of P 2 RX 7 gene polymorphisms are associated withboth cold pain sensitivity and analgesic effect of fentanyl

Background: The P2X7 receptor is a member of the P2X family of adenosine 5′-triphosphate-gated cation channels. Several recent studies have demonstrated that this receptor is involved in mechanisms related to pain and inflammation. However, unknown is whether polymorphisms of the P2RX7 gene that encodes the human P2X7 receptor influence pain sensitivity and analgesic effects of opioids. The P2RX7 gene is known to be highly polymorphic. Thus, the present study examined associations between fentanyl sensitivity and polymorphisms in the P2RX7 gene in 355 Japanese patients who underwent painful orofacial cosmetic surgery. Results: We first conducted linkage disequilibrium (LD) analyses for 55 reported single-nucleotide polymorphisms (SNPs) in the region within and around the P2RX7 gene using genomic samples from 100 patients. In our samples, 42 SNPs were polymorphic, and a total of five LD blocks with six Tag SNPs (rs2708092, rs1180012, rs1718125, rs208293, rs1718136, and rs7132846) were observed. Thus, we further analyzed associations between genotypes/haplotypes of these Tag SNPs and clinical data using a total of 355 samples. In the genotype-based association study, only the rs1718125 G > A SNP tended to be associated with higher pain scores on a visual analog scale 24 h after surgery (VAS24). The haplotype-based association study showed that subjects with homozygous haplotype No.3 (GTAAAC; estimated frequency: 15.0%) exhibited significantly higher cold pain sensitivity and lower analgesic effects of fentanyl for acute cold pain in the cold pressor test. Conversely, subjects who carried haplotype No.1 (ACGGAC; estimated frequency: 24.5%) tended to exhibit lower cold pain sensitivity and higher analgesic effects of fentanyl. Furthermore, subjects with homozygous haplotype No.2 (GCGGAC; estimated frequency: 22.9%) exhibited significantly lower VAS24 scores. Conclusions: Cold pain sensitivity and analgesic effects of fentanyl were related to the SNP and haplotypes of the P2RX7 gene. The patients with the rs1718125 G>A SNP tended to show higher VAS24 scores. Moreover, the combination of polymorphisms from the 5′-flanking region to exon 5 recessively affected cold pain sensitivity and analgesic effects of opioids for acute cold pain. The present findings shed light on the involvement of P2RX7 gene polymorphisms in naive cold pain sensitivity and analgesic effects of fentanyl.
Frontoparietal Activity with Minimal Decision and Control

In the human brain, a well known frontoparietal circuit, including lateral prefrontal cortex (LPFC), presupplementary motor area/anterior cingulate cortex (pre-SMA/ACC), and both the superior and inferior parietal cortex, is involved in cognitive control. One proposal is that the frontoparietal cortex holds a flexible description of attended or task-relevant information, biasing processing in favor of this information in many different parts of the brain. Here, we separate frontoparietal coding of attended information from its active use in behavior. In two experiments, subjects watch a stream of visual stimuli in a fixed location. In the first experiment, there is no task to perform; in the second, decisions are orthogonal to the occurrence of new stimulus events. Even in these simple circumstances, we find that attended stimulus changes give extensive activation of LPFC, pre-SMA/ACC and parietal cortex, whereas unattended changes do not. Even without behavior to control, these classical “control” regions are active in simple update of attended information.
LANGUAGE SKILLS IN CHILDREN WITH ADHD AND DEVELOPMENTAL DYSLEXIA

Background. Attention-Deficit Hyperactivity Disorder (ADHD) and specific learning difficulties (dyslexia) belong to the most frequently diagnosed developmental disorders in school-age children, and not infrequently cooccur. Linguistic functioning is one of the aspects of cognitive functioning in the cases of ADHA, dyslexia, or both disorders that presents a very diverse symptomatology. The aim of our interdisciplinary research, conducted on 259 children, was to determine whether or not children diagnosed with ADHD and developmental dyslexia differ in the level of linguistic functioning from their peers who are only hyperactive or have isolated developmental dyslexia. Material and methods. The experimental group consisted of 62 children diagnosed with both ADHD and dyslexia. This group was compared with two other clinical groups: children with ADHD and children with dyslexia, and to a control group of pupils without any diagnosed deficits, matched to the experimental group in terms of age. We used the Controlled Oral Word Association Test (COWAT), the Phonological-Semantic Interference Test, and the Token Test – 36, in order to analyze cognitive functioning. Results. Our results indicated that children from all three clinical groups showed a lower level of linguistic competence than the control group. ADHD children had the most difficulties with tasks measuring verbal fluency and comprehension of complex linguistic utterances. The dyslexic group had difficulties mainly with the phonological aspect of language. In the case of cooccurrence of both disorders, cognitive functions deficits are deeper, which must affect school performance. LANGUAGE SKILLS IN CHILDREN WITH ADHD AND DEVELOPMENTAL DYSLEXIA
Modeling microcapsule-enabled self-healing cementitious composite materials using discrete element method

Concrete with a micro-encapsulated healing agent is appealing due to its self-healing capacity. The discrete element method (DEM) is emerging as an increasingly used approach for investigating the damage phenomenon of materials at the microscale. It provides a promising way to study the microcapsule-enabled self-healing concrete. Based on the experimental observation and DEM, a three-dimensional damage-healing numerical model of microcapsule-enabled self-healing cementitious materials under compressive loading is proposed. The local healing effect can be simulated in our model, as well as the stress concentration effect and the partial healing effect. The healing variable of the DEM model is developed to describe the healing process. We examine the dependence of the mechanical properties of the microcapsule-enabled self-healing material on (a) the stiffness of the solidified healing agent, (b) the strength of the solidified healing agent, (c) the initial damage of specimens, and (d) the partial healing effect. In particular, the proposed numerical damage-healing model demonstrates the potential capability to explain and simulate the physical behavior of microcapsule-enabled self-healing materials on the microscale.
Children's physical activity and physical self-perceptions

The aim of this study was to determine the relationship between physical self-perceptions and physical activity in Canadian school children aged 10–14 years. The sample consisted of 220 boys and 246 girls in grades 5–8. Physical activity was assessed by 7-day recall using the Physical Activity Questionnaire for Older Children. Selfperceptions of physical conditioning, sports competence, strength, body appearance and general physical selfworth were measured by the Physical Self-Perception Profile (PSPP). We found that boys were more physically active than girls and had higher perceptions of sport competence and strength. All PSPP scales were significantly correlated with physical activity in both boys and girls. Structural equation modelling procedures found the hierarchical PSPP model provided a good fit to the observed data, with little evidence of diff erences between the sexes. Analysis of five alternative structural models of the relationship between the PSPP and physical activity found the most parsimonious model to have significant pathways from both physical conditioning and sport skills to physical activity. Models for the sample as a whole, for boys and for girls were similar, accounting for an R 2 of 0.27–0.29 for physical activity. Our results demonstrate that physical self-perceptions, especially physical conditioning and sport skills, are significant correlates of activity in this population.
Successful transfer of Sandia National Laboratories' outdoor test technology to TÜV Rheinland Photovoltaic Testing Laboratory

Sandia National Laboratories (Sandia) has observed an increased demand for high accuracy outdoor photovoltaic (PV) module characterization using Sandia's Photovoltaic Array Performance Model [1]. To meet this demand, Sandia entered into a competitively-bid agreement in May 2009 with TÜV Rheinland Photovoltaic Testing Laboratory (TÜV-PTL) to transfer Sandia's capability to fully characterize standard, commercial-scale PV modules. Sandia and TÜV-PTL worked closely on two round-robin experiments and months of subsequent work and discussions that resulted in module performance output calculations agreeing to within +/−2.5%.