Miracle-dz/UniFAR-FTUs huggingface dataset:
The uORF-containing thrombopoietin mRNA escapes nonsense-mediated decay (NMD)

Platelet production is induced by the cytokine thrombopoietin (TPO). It is physiologically critical that TPO expression is tightly regulated, because lack of TPO causes life-threatening thrombocytopenia while an excess of TPO results in thrombocytosis. The plasma concentration of TPO is controlled by a negative feedback loop involving receptor-mediated uptake of TPO by platelets. Furthermore, TPO biosynthesis is limited by upstream open reading frames (uORFs) that curtail the translation of the TPO mRNA. uORFs are suggested to activate RNA degradation by nonsense-mediated decay (NMD) in a number of physiological transcripts. Here, we determine whether NMD affects TPO expression. We show that reporter mRNAs bearing the seventh TPO uORF escape NMD. Importantly, endogenously expressed TPO mRNA from HuH7 cells is unaffected by abrogation of NMD by RNAi. Thus, regulation of TPO expression is independent of NMD, implying that mRNAs bearing uORFs cannot generally be considered to represent NMD targets.
Beverage purchases from stores in Mexico under the excise tax on sugar sweetened beverages: observational study

Study question What has been the effect on purchases of beverages from stores in Mexico one year after implementation of the excise tax on sugar sweetened beverages? Methods In this observational study the authors used data on the purchase of beverages in Mexico from January 2012 to December 2014 from an unbalanced panel of 6253 households providing 205 112 observations in 53 cities with more than 50 000 inhabitants. To test whether the post-tax trend in purchases was significantly different from the pretax trend, the authors used a difference in difference fixed effects model, which adjusts for both macroeconomic variables that can affect the purchase of beverages over time, and pre-existing trends. The variables used in the analysis included demographic information on household composition (age and sex of household members) and socioeconomic status (low, middle, and high). The authors compared the predicted volumes (mL/capita/day) of taxed and untaxed beverages purchased in 2014—the observed post-tax period—with the estimated volumes that would have been purchased if the tax had not been implemented (counterfactual) based on pretax trends. Study answer and limitations Relative to the counterfactual in 2014, purchases of taxed beverages decreased by an average of 6% (−12 mL/capita/day), and decreased at an increasing rate up to a 12% decline by December 2014. All three socioeconomic groups reduced purchases of taxed beverages, but reductions were higher among the households of low socioeconomic status, averaging a 9% decline during 2014, and up to a 17% decrease by December 2014 compared with pretax trends. Purchases of untaxed beverages were 4% (36 mL/capita/day) higher than the counterfactual, mainly driven by an increase in purchases of bottled plain water. What this study adds The tax on sugar sweetened beverages was associated with reductions in purchases of taxed beverages and increases in purchases of untaxed beverages. Continued monitoring is needed to understand purchases longer term, potential substitutions, and health implications. Funding, competing interests, data sharing This work was supported by grants from Bloomberg Philanthropies and the Robert Wood Johnson Foundation and by the Instituto Nacional de Salud Pública and the Carolina Population Center. The authors have no competing interests. No additional data are available.
Incidence trends for human papillomavirus-related and -unrelated oral squamous cell carcinomas in the United States.

PURPOSE To investigate the impact of human papillomavirus (HPV) on the epidemiology of oral squamous cell carcinomas (OSCCs) in the United States, we assessed differences in patient characteristics, incidence, and survival between potentially HPV-related and HPV-unrelated OSCC sites. PATIENTS AND METHODS Data from nine Surveillance, Epidemiology, and End Results program registries (1973 to 2004) were used to classify OSCCs by anatomic site as potentially HPV-related (n = 17,625) or HPV-unrelated (n = 28,144). Joinpoint regression and age-period-cohort models were used to assess incidence trends. Life-table analyses were used to compare 2-year overall survival for HPV-related and HPV-unrelated OSCCs. RESULTS HPV-related OSCCs were diagnosed at younger ages than HPV-unrelated OSCCs (mean ages at diagnosis, 61.0 and 63.8 years, respectively; P < .001). Incidence increased significantly for HPV-related OSCC from 1973 to 2004 (annual percentage change [APC] = 0.80; P < .001), particularly among white men and at younger ages. By contrast, incidence for HPV-unrelated OSCC was stable through 1982 (APC = 0.82; P = .186) and declined significantly during 1983 to 2004 (APC = -1.85; P < .001). When treated with radiation, improvements in 2-year survival across calendar periods were more pronounced for HPV-related OSCCs (absolute increase in survival from 1973 through 1982 to 1993 through 2004 for localized, regional, and distant stages = 9.9%, 23.1%, and 18.6%, respectively) than HPV-unrelated OSCCs (5.6%, 3.1%, and 9.9%, respectively). During 1993 to 2004, for all stages treated with radiation, patients with HPV-related OSCCs had significantly higher survival rates than those with HPV-unrelated OSCCs. CONCLUSION The proportion of OSCCs that are potentially HPV-related increased in the United States from 1973 to 2004, perhaps as a result of changing sexual behaviors. Recent improvements in survival with radiotherapy may be due in part to a shift in the etiology of OSCCs.
A Phase I Pharmacokinetic and Biological Correlative Study of IMP321, a Novel MHC Class II Agonist, in Patients with Advanced Renal Cell Carcinoma

Purpose: To evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of IMP321, a recombinant soluble LAG-3Ig fusion protein which agonizes MHC class II–driven dendritic cell activation. Experimental Design: Patients with advanced renal cell carcinoma were treated with escalating doses of IMP321 s.c. Blood samples were assayed to determine plasma pharmacokinetic parameters, detect human anti-IMP321 antibody formation, and determine long-lived CD8 T cell responses. Results: Twenty-one advanced renal cell carcinoma patients received 119 injections of IMP321 at doses ranging from 0.050 to 30 mg/injection s.c. biweekly for 6 injections. No clinically significant adverse events were observed. Good systemic exposure to the product was obtained following s.c. injections of doses above 6 mg. IMP321 induced both sustained CD8 T-cell activation and an increase in the percentage of long-lived effector-memory CD8 T cells in all patients at doses above 6 mg. Tumor growth was reduced and progression-free survival was better in those patients receiving higher doses (>6 mg) of IMP321: 7 of 8 evaluable patients treated at the higher doses experienced stable disease at 3 months compared with only 3 of 11 in the lower dose group (P = 0.015). Conclusion: The absence of toxicity and the demonstration of activity at doses above 6 mg warrant further disease-directed studies of IMP321 in combined regimens (e.g., chemoimmunotherapy). (Clin Cancer Res 2009;15(19):6225–31)
The weakness of integrity protection for LTE

In this paper, we concentrate on the security issues of the integrity protection of LTE. EIA1 and EIA3, two integrity protection algorithms of LTE, are insecure if the initial value (IV) can be repeated twice during the life cycle of an integrity key (IK). Especially for EIA1, because of its linearity, given two valid Message Authentication Codes (MACs) our algorithm can forge up to 232 valid MACs. Thus, the probability of finding a valid MAC is dramatically increased. Although the combination of IV and IK never repeats in the ordinary case, in our well-designed scenario, the attacker can make the same combination occur twice. The duplication provides the opportunity to conduct our linear forgery attack, which may harm the security of communication. To test our linear forgery attack algorithm, we generated two counter check messages and successfully forged the third one. We also examined the attack timing by simulating real communication. From the experimental results, our attack is applicable.
Luteolin Reduces Alzheimer’s Disease Pathologies Induced by Traumatic Brain Injury

Traumatic brain injury (TBI) occurs in response to an acute insult to the head and is recognized as a major risk factor for Alzheimer’s disease (AD). Indeed, recent studies have suggested a pathological overlap between TBI and AD, with both conditions exhibiting amyloid-beta (Aβ) deposits, tauopathy, and neuroinflammation. Additional studies involving animal models of AD indicate that some AD-related genotypic determinants may be critical factors enhancing temporal and phenotypic symptoms of TBI. Thus in the present study, we examined sub-acute effects of moderate TBI delivered by a gas-driven shock tube device in Aβ depositing Tg2576 mice. Three days later, significant increases in b-amyloid deposition, glycogen synthase-3 (GSK-3) activation, phospho-tau, and pro-inflammatory cytokines were observed. Importantly, peripheral treatment with the naturally occurring flavonoid, luteolin, significantly abolished these accelerated pathologies. This study lays the groundwork for a safe and natural compound that could prevent or treat TBI with minimal or no deleterious side effects in combat personnel and others at risk or who have experienced TBI.
ACM SIGSOFT SOFTWARE ENGINEERING NOTES Vol 8 No 3 Jul 1983 Page 1 2 CRITERIA FOR SOFTWARE RELIABILITY MODEL COMPARISONS

A set of criteria is proposed for the comparison of software reliability models . The intention is to provid e a logically organized basis for determining the superior models and for the presentation of model characteristics . It is hoped that in the future, a software manager will be able to more easily select th e model most suitable for his/her requirements fro m among the preferred ones .
Leukocyte Adhesion in Endothelial Cells Induce Inflammatory Molecules and Sphingosine-1-Phosphate Cooperate To Lipopolysaccharide

Given that TLRs and sphingosine-1-phosphate (S1P) are key players in inflammation, we explored the potential interplay between TLRs and S1P in the adhesion/inflammatory pathways in primary human endothelial cells. As determined by Western blot and flow cytometry, cells treated with LPS (a TLR4 ligand) and S1P showed significantly enhanced expression of adhesion molecules such as ICAM-1 and E-selectin compared with the effect of either ligand alone. Cell-type differences on E-selectin upregulation were observed. In contrast, no cooperation effect on ICAM-1 or E-selectin was observed with a TLR2/TLR1 ligand. Consistent with an increase in adhesion molecule expression, endothelial cell treatment with LPS plus S1P significantly enhanced adhesion of PBMCs under shear stress conditions compared with the effect of either ligand alone and exhibited comparable levels of cell adhesion strength as those after TNF-a treatment. Moreover, LPS and S1P cooperated to increase the expression of proinflammatory molecules such as IL-6, cyclooxygenase-2, and prostacyclin, as determined by ELISA and Western blot. The analysis of signaling pathways revealed the synergistic phosphorylation of ERK upon LPS plus S1P treatment of HUVEC and human aortic endothelial cells and cell-type differences on p38 and NF-kB activation. Moreover, pharmacological and small interfering RNA experiments disclosed the involvement of S1P 1/3 and NF-kB in the cooperation effect and that cell origin determines the S1P receptors and signaling routes involved. Sphingosine kinase activity induction upon LPS plus S1P treatment suggests S1P– Sphingosine kinase axis involvement. In summary, LPS and S1P cooperate to increase proinflammatory molecules in endothelial cells and, in turn, to augment leukocyte adhesion, thus exacerbating S1P-mediated proadhesive/proinflammatory properties. S phingosine-1-phosphate (S1P) is a bioactive lipid mediator that mediates a wide spectrum of cell functions in both intracellular and extracellular compartments, which includes proliferation, migration, differentiation, angiogenesis, and lymphocyte trafficking (1–3). Many of the actions of S1P are mediated by the activation of receptors, initially known as endo-thelial differentiation genes and now designated as S1P 1–5 , which are high-affinity receptors coupled to G proteins (a io , a q , or a 12/13) that trigger the activation of multiple signals leading to specific cell responses (4). In addition, S1P can play an important role as a second messenger during inflammation (2). Accumulating evidence suggests an important role of S1P in the regulation of the immune system and the vascular system (2, 5). The S1P–S1P-receptor signaling axis has been implicated in a variety of pathophysiological conditions and diseases such …
Impaired emotion regulation in schizophrenia: evidence from event-related potentials

Background Although several aspects of emotion seem to be intact in schizophrenia, there is emerging evidence that patients show an impaired ability to adaptively regulate their emotions. This event-related potential (ERP) study examined whether schizophrenia is associated with impaired neural responses to appraisal frames, that is when negative stimuli are presented in a less negative context. Method Thirty-one schizophrenia out-patients and 27 healthy controls completed a validated picture-viewing task with three conditions: (1) neutral pictures preceded by neutral descriptions (‘Neutral’), (2) unpleasant pictures preceded by negative descriptions (‘Preappraised negative’), and (3) unpleasant pictures preceded by more neutral descriptions (‘Preappraised neutral’). Analyses focused on the late positive potential (LPP), an index of facilitated attention to emotional stimuli that is reduced following cognitive emotion regulation strategies, during four time windows from 300 to 2000 ms post-picture onset. Results Replicating prior studies, controls showed smaller LPP in Preappraised neutral and Neutral versus Preappraised negative conditions throughout the 300–2000-ms time period. By contrast, patients showed (a) larger LPP in Preappraised neutral and Preappraised negative versus Neutral conditions in the initial period (300–600 ms) and (b) an atypical pattern of larger LPP to Preappraised neutral versus Preappraised negative and Neutral conditions in the 600–1500-ms epochs. Conclusions Modulation of neural responses by a cognitive emotion regulation strategy seems to be impaired in schizophrenia during the first 2 s after exposure to unpleasant stimuli.
Formation of cell junctions between grafted and host cardiomyocytes at the border zone of rat myocardial infarction.

BACKGROUND Cardiomyocyte transplantation is an innovative strategy for the treatment of heart failure after myocardial infarction. Cell junctions show diverse temporal polarization toward intercalated disks during postnatal development and exhibit altered distribution in diseased hearts. To elucidate the formation of cell junctions between grafted and host cardiomyocytes at the border zone of myocardial infarction, the 3D distribution of cell junctions was examined using immunohistochemistry and confocal microscopy. METHODS AND RESULTS Neonatal cardiomyocytes obtained from 3-day-old rats by collagenase digestion and Percoll density centrifugation were injected into the border zones of infarction sites 10 days after coronary ligation in adult rats. At 4 to 14 days after transplantation, hearts were harvested and processed by immunohistochemistry. Antibodies against connexin43, desmoplakin, and cadherin were used to analyze the distribution of gap junctions, desmosomes, and adherens junctions, respectively. Grafted cardiomyocytes were identified by immunohistochemistry for alpha-smooth muscle actin. Grafted cardiomyocytes tended to align parallel to the host cardiomyocytes. Connexin43, desmoplakin, and cadherin were localized between grafted cardiomyocytes themselves and between grafted and host cardiomyocytes. Semiquantitative analysis revealed that all junctions showed increasing polarization to longitudinal cell termini, especially at the border of grafted and host cardiomyocytes, as time advanced from 4 to 7 days after transplantation. CONCLUSIONS These findings indicate that grafted cardiomyocytes foster electrical pathways with host counterparts through the gap junction and suggest that the environment in infarcted hearts could influence the localization of gap junctions, desmosomes, and adherens junctions.
Lack of facilities rather than sociocultural factors as the primary barrier to physical activity among female Saudi university students

Purpose The Kingdom of Saudi Arabia is experiencing a dramatic increase in physical inactivity, with women having higher levels of inactivity than men among all age groups. It is assumed that factors such as dress codes, restrictions on going outdoors, and conservative norms are the main reasons for women’s low physical activity. Our aim was to explore the different parameters related to physical activity, including self-efficacy, as well as the perceived barriers to and benefits of physical activity in young Saudi females. Patients and methods Ninety-four first-year female Saudi university students in Riyadh, Kingdom of Saudi Arabia, participated in the present study in 2014. The students were from eight bachelor’s programs in health and well-being, and each completed a questionnaire with questions divided into five parts as follows: 1) socioeconomic status, 2) physical activity, 3) self-efficacy 4) social factors, and 5) barriers and facilitators related to physical activity. Results The students exercised at home and alone, and there was low self-efficacy for physical activity (mean score =42±14). Among social factors, attending university was the only factor that hindered physical activity (32%). Physical activity was positively perceived overall (mean score =131±10). Students showed awareness of the benefits of physical activity for health and well-being. The most important barrier was the lack of designated areas available for physical activity. Students disagreed that family or the Islamic community were barriers to physical activity. Conclusion The lack of facilities and lack of encouragement from the university, but not a lack of knowledge (a high level of knowledge is to be expected given their health and well-being studies backgrounds) and/or restrictions from families and society, seem to hinder female students’ physical activity, at least young Saudi students.
PRNP allelic series from 19 years of prion protein gene sequencing at the MRC Prion Unit

Mutation of the human prion protein gene (PRNP) open reading frame (ORF) accounts for almost all reported familial concurrence of prion disease. The more common mutations globally: octapeptide repeat insertions, P102L, D178N, E200K, and V210I have occurred in large multigenerational pedigrees and display autosomal dominant inheritance, however, many rare genetic changes have been reported that are of uncertain pathogenicity. Based on 19 years of PRNP sequencing at the MRC Prion Unit, London, and analysis of 3664 samples from patients referred with suspected prion disease and healthy populations, we present novel allele combinations, healthy control population data, results of screening the PRNP ORF in DNA from the entire referral series and the CEPH human genome diversity cell line panel. Of the 10 alleles detected in patients for which detailed cases histories are presented, 4 are unreported (G54S, D167N, V209M, Q212PP), two changes are thought to be pathogenic but have not been described in our regions (P105L from the UK, G114V from India and Turkey), and the remainder reported in healthy control populations or in trans to known pathogenic mutations suggesting non‐ or low pathogenicity (G54S, 1‐OPRI, G142S, N171S, V209M, E219K). New genotype‐phenotype correlations and population frequencies presented will help the diagnosis and genetic counselling of those with suspected inherited prion disease. © 2010 Wiley‐Liss, Inc.
Diabetes Mellitus Receptor Antagonist S 18886 Prevents Enhanced Atherogenesis 2 The Thromboxane

Weisbrod, Mengwei Zang, Shanqin Xu, Bingbing Jiang, Jennifer M. Oliver-Krasinski, Antonio Adriana Zuccollo, Chaomei Shi, Roberto Mastroianni, Karlene A. Maitland-Toolan, Robert M. Caused by Diabetes Mellitus Receptor Antagonist S18886 Prevents Enhanced Atherogenesis 2 The Thromboxane A Print ISSN: 0009-7322. Online ISSN: 1524-4539 Copyright © 2005 American Heart Association, Inc. All rights reserved. is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231 Circulation doi: 10.1161/CIRCULATIONAHA.105. 581892 2005;112:3001-3008; originally published online October 31, 2005; Circulation. http://circ.ahajournals. org/content/112/19/3001 World Wide Web at: The online version of this article, along with updated information and services, is located on the
A Molecular Dynamics Simulation Study on the Relationship between Hydrogen Bond and Damping Properties of AO-70/NBR Composites

This work was try to study the number and types of hydrogen bonds (H-bonds) formed in hindered phenol AO-70/nitrile butadiene rubber (NBR) composites and their contributions to the damping properties by molecular dynamic (MD) simulation and experimental methods. MD simulation results showed that there were four types of H-bonds, namely, type A (AO-70) –OH.NC– (NBR) H-bonds in AO-70/NBR composites, type B (AO-70) –OH.O=C– (AO-70) H-bonds, type C (AO-70) –OH.OH–(AO-70) and D (AO-70) –OH.O–C– (AO-70) H-bonds, what's more, type A and type B H-Bonds formed more easily than others. Fourier transform infrared spectroscopy (FTIR) confirmed the existence of H-bonds. Meanwhile, the AO-70/NBR composites with AO-70 content of 109 phr had the largest number of H-bonds, smallest fractional free volume (FFV) and resulting in the optimistic damping performance of the composites.
Some observations on the cardio-vascular system in the viable foetal lamb.

DURING the seasons 1937-8 and 1938-9 we co-operated with Sir Joseph Barcroft and Dr D. H. Barron in X-ray cinematographic studies that had as their initial object the determination of the time of functional closure of the ductus arteriosus. These studies led to observations upon the foetal circulation as a whole, and of them we have published a preliminary account (Barclay et al. 1939), together with notes on the identification of the ductus arteriosus in radiographs. An account of the functional closure of the ductus, comprising evidence from blood-gas analyses and from X-ray cinematographic records, is to be published elsewhere, and there will also be presented at some future date a detailed analysis of all our radiological data.
Stochastic Resonance in Continuous and Spiking Neuron Models With Levy Noise

Levy noise can help neurons detect faint or subthreshold signals. Levy noise extends standard Brownian noise to many types of impulsive jump-noise processes found in real and model neurons as well as in models of finance and other random phenomena. Two new theorems and the ItÔ calculus show that white Levy noise will benefit subthreshold neuronal signal detection if the noise process's scaled drift velocity falls inside an interval that depends on the threshold values. These results generalize earlier “forbidden interval” theorems of neuronal “stochastic resonance” (SR) or noise-injection benefits. Global and local Lipschitz conditions imply that additive white Levy noise can increase the mutual information or bit count of several feedback neuron models that obey a general stochastic differential equation (SDE). Simulation results show that the same noise benefits still occur for some infinite-variance stable Levy noise processes even though the theorems themselves apply only to finite-variance Levy noise. The Appendix proves the two ItÔ-theoretic lemmas that underlie the new Levy noise-benefit theorems.