Miracle-dz/UniFAR-FTUs huggingface dataset:
Spinal NMDA Receptors and Nociception-evoked Release of Primary Afferent Substance P

Dorsal horn NMDA receptors contribute significantly to spinal nociceptive processing through an effect postsynaptic to non-primary glutamatergic axons, and perhaps presynaptic to the primary afferent terminals. The present study sought to examine the regulatory effects of NMDA receptors on primary afferent release of SP, as measured by neurokinin 1 receptor (NK1r) internalization in the spinal dorsal horn of rats. The effects of intrathecal NMDA alone or in combination with D-serine (a glycine site agonist) was initially examined on basal levels of NK1r internalization. NMDA alone or when co-administered with D-serine failed to induce NK1r internalization, whereas activation of spinal TRPV1 receptors by capsaicin resulted in a notable NK1r internalization. To determine whether NMDA receptor activation could potentiate NK1r internalization or pain behavior induced by a peripheral noxious stimulus, intrathecal NMDA was given prior to an intraplantar injection of formalin. NMDA did not alter the formalin-induced NK1r internalization nor did it enhance the formalin paw flinching behavior. To further characterize the effects of presynaptic NMDA receptors, the NMDA antagonists AP-5 and MK-801 were intrathecally administered to assess their regulatory effects on formalin-induced NK1r internalization and pain behavior. AP-5 had no effect on formalin-induced NK1r internalization, whereas MK-801 produced only a modest reduction. Both antagonists, however, reduced the formalin paw flinching behavior. In subsequent in vitro experiments, perfusion of NMDA in spinal cord slice preparations did not evoke basal release of SP or calcitonin gene-related peptide (CGRP). Likewise, perfusion of NMDA did not enhance capsaicin-evoked release of the two peptides. These results suggest that presynaptic NMDA receptors in the spinal cord play little if any role on the primary afferent release of SP. of
Hepatocyte HIF-1 and Intermittent Hypoxia Independently Impact Liver Fibrosis in Murine Nonalcoholic Fatty Liver Disease

Obstructive sleep apnea is associated with insulin resistance, lipid dysregulation, and hepatic steatosis and fibrosis in nonalcoholic fatty liver disease (NAFLD). We have previously shown that hepatocyte HIF-1 (hypoxia-inducible factor-1) mediates the development of liver fibrosis in a mouse model of NAFLD. We hypothesized that intermittent hypoxia (IH) modeling obstructive sleep apnea would worsen hepatic steatosis and fibrosis in murine NAFLD, via HIF-1. Mice with hepatocyte-specific deletion of Hif1a ( Hif1a 2 / 2 hep ) and wild-type ( Hif1a F/F ) controls were fed a high trans -fat diet to induce NAFLD with steatohepatitis. Half from each group were exposed to IH, and the other half were exposed to intermittent air. A glucose tolerance test was performed just prior to the end of the experiment. Mitochondrial efficiency was assessed in fresh liver tissue at the time of death. The hepatic malondialdehyde concentration and proinflammatory cytokine levels were assessed, and genes of collagen and fatty acid metabolism were examined. Hif1a 2 / 2 hep mice gained less weight than wild-type Hif1a mice ( 2 2.3 g, P = 0.029). There was also a genotype-independent effect of IH on body weight, with less weight gain in mice exposed to IH ( P = 0.003). Fasting glucose, homeostatic model assessment for insulin resistance, and glucose tolerance test results were all improved in Hif1a 2 / 2 hep mice. Liver collagen was increased in mice exposed to IH ( P = 0.033) and was reduced in Hif1a 2 / 2 hep mice ( P , 0.001), without any significant exposure/genotype interaction being demonstrated. Liver TNF- a and IL-1 b were significantly increased in mice exposed to IH and were decreased in Hif1a 2 / 2 hep mice. We conclude that HIF-1 signaling worsens the metabolic profile and hastens NAFLD progression and that IH may worsen liver fibrosis. These effects are plausibly mediated by hepatic inflammatory stress.
A Seismic Design Procedure for Moment-Frame Structures

ABSTRACT A procedure for the performance-based seismic design of moment-resistant frames is presented. The design procedure utilizes an estimate of the yield displacement of the roof in conjunction with yield point spectra to determine the required lateral strength. Beam strengths are established using a plastic mechanism approach, while a modified Portal Frame method is used to establish the strengths of critical sections of columns, considering the locations of inflection points and the desire to avoid weak-story mechanisms. An example illustrates the application to reinforced concrete frames. Due to the stability of the yield displacement, few (if any) iterations are needed.
Factors Associated with Withdrawal from Dialysis Therapy in Very-Elderly Incident Hemodialysis Patients

Objectives: Among very-elderly kidney disease patients progressing to end-stage renal disease, there is growing interest in conservative non-dialytic management approaches. However, among those who have initiated hemodialysis, little is known about the impact of withdrawal from dialysis on mortality, nor the patient characteristics associated with withdrawal from dialysis. Study Design: Historical cohort study. Setting and Participants: We examined 133,162 incident hemodialysis patients receiving care within a large national dialysis organization from 2007-2011. Measures: We identified patients who withdrew from dialysis, either as a listed cause of death or censor reason. Incidence-rates and sub-distribution hazard-ratios for withdrawal from dialysis as well as four other censoring reasons were examined across age groups. In addition, demographic and clinical characteristics associated with withdrawal from dialysis therapy among patients in the very elderly age range ( ⩾ 80 years old) was assessed using logistic regression analysis. Results: Incident-rates of withdrawal from dialysis were markedly higher compared to other censoring reasons for each age group. Additionally, compared to the youngest age group, incidence of withdrawal from dialysis incrementally increased across older age groups. Among patients ≥80 years, factors associated with higher odds of dialysis withdrawal included non-Hispanic white ethnicity, having Medicare/Medicaid insurance, dementia, mid-west geographic region, and less favorable markers associated with malnutrition-inflammation-cachexia syndrome (MICS) such as high white blood cell counts and low body mass index, albumin, and normalized protein catabolic rate. Conclusion/Implications: Among incident hemodialysis patients, dialysis therapy withdrawal was associated with older age, non-Hispanic white race, dementia, mid-west region and less favorable MICS status. Further studies examining withdrawal from dialysis in elderly patients are needed. Previous shown a between race/ethnicity likelihood of from strata, , , 24 , 25 In our cohort,
Evolution, Emotion, & Episodic Engagement

Rodent research provides important insights into neural correlates of human psychology, but new cortical areas, connections, and cognitive abilities emerged during primate evolution, including human evolution. Comparison of human brains with those of nonhuman primates reveals two aspects of human brain evolution particularly relevant to emotional disorders: expansion of homotypical association areas and expansion of the hippocampus. Two uniquely human cognitive capacities link these phylogenetic developments with emotion: (i) a subjective sense of participating in and re-experiencing remembered events; and (ii) a limitless capacity to imagine details of future events. These abilities provided evolving humans with selective advantages, but they also created proclivities for emotional problems. The first capacity evokes the “reliving” of past events in the “here-and-now”, accompanied by emotional responses that occurred during memory encoding. It contributes to risk for stress-related syndromes, such as post-traumatic stress disorder. The second capacity, an ability to imagine future events without temporal limitations, facilitates flexible, goal-related behavior by drawing on and creating a uniquely rich array of mental representations. It promotes goal achievement and reduces errors, but the mental construction of future events also contributes to developmental aspects of anxiety and mood disorders. With maturation of homotypical association areas, the concrete concerns of childhood expand to encompass the abstract apprehensions of adolescence and adulthood. These cognitive capacities and their dysfunction are amenable to a research agenda that melds experimental therapeutic interventions, cognitive neuropsychology, and developmental psychology in both humans and nonhuman primates.
The St. George ’ s Respiratory Questionnaire De ﬁ nition of Chronic Bronchitis May Be a Better Predictor of COPD Exacerbations Compared With the Classic De ﬁ nition

BACKGROUND: Chronic bronchitis (CB) increases risk of COPD exacerbations. We have shown that the St. George ’ s Respiratory Questionnaire (SGRQ) CB de ﬁ nition identi ﬁ es patients with a similar clinical phenotype as classically de ﬁ ned CB. Whether the SGRQ CB de ﬁ nition is a predictor of future COPD exacerbations is unknown. METHODS: We analyzed 7,557 smokers with normal spirometry and Global Initiative for Chronic Obstructive Lung Disease stage 1-4 COPD in the Genetic Epidemiology of COPD study with longitudinal follow-up data on exacerbations. Subjects were divided into classic CB þ or classic CB – , using the classic de ﬁ nition. In addition, subjects were divided into SGRQ CB þ or SGRQ CB – . Exacerbation frequency and severe exacerbation frequency were determined in each group. Multivariable linear regressions were performed for exacerbation frequency with either classic CB or SGRQ CB and relevant covariates. RESULTS: There were 1,434 classic CB þ subjects and 2,290 SGRQ CB þ subjects. The classic CB þ group had a greater exacerbation frequency compared with the classic CB – group (0.69 (cid:2) 1.26 vs 0.36 (cid:2) 0.90 exacerbations per patient per year; P < . 0001) and a greater severe exacerbation frequency (0.26 (cid:2) 0.74 vs 0.13 (cid:2) 0.46 severe exacerbations per patient per year; P < . 0001). There were similar differences between the SGRQ CB þ and SGRQ CB – groups. In multivariable analysis, both SGRQ CB and classic CB were independent predictors of exacerbation frequency, but SGRQ CB had a higher regression coef ﬁ cient. In addition, SGRQ CB was an independent predictor of severe exacerbation frequency whereas classic CB was not. CONCLUSIONS: The SGRQ CB de ﬁ nition identi ﬁ ed more subjects at risk for future exacerbations than the classic CB de ﬁ nition. SGRQ CB was at least a similar if not better predictor of future exacerbations than classic CB. CB þ ), continuous variables were analyzed by one-way analysis of variance with the Bonferroni method for multiple comparisons. Multivariable linear regression for total and severe exacerbation frequency in LFU was performed with either classic CB or SGRQ CB as the independent variables of interest with age, race, sex, pack-year history, current smoking, oxygen use, modi ﬁ ed Medical Research Council (mMRC) dyspnea score, % emphysema, prior exacerbation frequency, FEV 1 % predicted, 6-minute walk distance, and body mass index as covariates. The regression coef ﬁ cients for SGRQ CB and classic CB were compared with one another in these multivariable models. In addition, multivariable logistic regression was performed for exacerbation frequency $ 2 exacerbations/subject/year and severe exacerbation frequency $ 1 exacerbation/subject/year, using the same independent variables.
ROLE OF CHROMATIN ACCESSIBILITY IN THE OCCUPANCY AND TRANSCRIPTION OF THE INSULIN GENE BY THE PANCREATIC TRANSCRIPTION FACTOR PDX-1

Pdx-1 is a hox-like transcription factor that is responsible for the activation of the insulin gene. Prior studies have demonstrated the interaction in vitro of Pdx-1 with short (20-40 nucleotide) DNA fragments corresponding to “A boxes” of the insulin promoter. Precisely how Pdx-1 binds to DNA in the complex milieu of chromatin, however, has never been studied. Here, we explored how Pdx-1-DNA interactions might be influenced by chromatin accessibility at the insulin gene in β cells ( β TC3) vs. pancreatic ductal cells (mPAC). We demonstrate that Pdx-1 occupies the endogenous insulin promoter in β TC3 cells but not in mPAC cells, a finding that is independent of the intracellular Pdx-1 protein concentration. Based on micrococcal nuclease protection assays, the difference in promoter binding between the two cell types appears to be secondary to chromatin accessibility at predicted Pdx-1 binding sites between bp −126 to −296 (relative to the transcriptional start site) of the insulin promoter. Binding studies using pruified Pdx-1 and reconsituted chromatin in vitro suggest that the positioning of a nucleosome(s) within this crucial region of the promoter might account for differences in chromatin accessibility. Consistent with these observations, fluorescence colocalization studies show that Pdx-1 does not occupy regions of compacted, nucleosome-rich chromatin within the nucleus. Our findings suggest a model whereby insulin transcription in the β cell is at least partially facilitated by enahanced chromatin accessibility within a of the nucleosome. We propose a model whereby insulin transcription in the β cell is at least at least partially facilitated by enhanced accessibility of chromatin within a crucial regulatory region.
Experimental evaluation of different hydrodynamic modelling techniques applied to the ISWEC

The appropriate numerical modelling of a Wave Energy Converter behaviour is crucial for both the initial design phase (loadings estimations) and the productivity assessment of the real device, working in a certain installation site. The most difficult aspect to be modelled are the floater motions at resonance conditions, where motions amplitude are emphasised. Several techniques can be used, ranging from the linear Cummins' equation to fully viscous CFD simulations. This paper deals with the implementation of the 3 DOFs linear hydrodynamic model developed for the time-domain simulation of ISWEC (Inertial Sea Wave Energy Converter) device. The main advantage of the model here presented is its low computational cost. A first benchmarking between the numerical model and a series of tank testing experiments, carried out on a scaled ISWEC floater prototype, is described. Experimental results are used for the identification of the non-linearity due to the viscous effects. The novelty of the identification approach is the estimation of the non-linearity contribution along each DOF taken into account. A second comparison is done against the open source code WEC-Sim that allows the calculation of the floater instantaneous wetted surface, with the aim of obtaining a cost-benefit evaluation of the different modelling techniques.
The SEDs Database to Study Evolution of Radio Galaxies

The project of the informational system creation on the problem of evolution of radio galaxies is described. This system, being developed at present, will allow a user to operate with simulated curves of spectral energy distributions (SED) and to estimate ages and redshifts by photometrical data. Planned modes of access, formats of output result and additional functions are described. The last few years have changed our view on the evolution of galaxies: the most distant galaxies (Le. systems having stellar population) have been found at z=6.68 (Chen et aI., 1999) and radio galaxies at z=5.2 (van Breugel et aI., 1999). To understand deeper a situation with a stellar population of host galaxies and to check various mordern models it is very important to have a capability to detect correctly an age of galaxies. The labour intensity of obtaining statistically significant high-quality data on distant and faint galaxies and radio galaxies forces one to look for simple indirect procedures in the determination of redshifts and other characteristics of these objects. With regard to radio galaxies, even photometric estimates turned out to be helpful and have so far been used (McCarthy, .1993). Over the last few years the three models: PEGASE (Project de'Etude des Galaxies par Synthese Evolutive (Fioc and Rocca-Volmerange, 1997)), Poggianti (1997) and GISSEL'96 (Bruzual, Charlot, 1996), have been extensively used, in which an attempt has been made to eliminate the shortcomings of the previous versions. In the "Big Trio" experiment (Parijskij et aI., 1996) we also attempted to apply these techniques to distant objects of the RC catalogue with ultra steep spectra (USS). Color data for nearly the whole basic sample of USS FRII (Fanaroff and Riley, 1974) RC objects have been obtained with the 6m telescope of SAO RAS. To accelerate a procedure of age (and photometric redshift) estimation we have begun a project "Evolution of radio galaxies", supported by the Russian Foundation of Basic Research (grant No.99-07-90334), which has to allow a user to obtain age and photometric redshift estimations. 1. Description of a system This system, being developed at present, will allow a user to operate with simulated curves of spectral energy distributions (SED) to estimate ages and redshifts by photometral data. Authors use SEDs of three models: (1) PEGASE, (2) Poggianti(1996)) and (3) GISSEL'96. for different types of galaxies.
Dysfunctional ErbB2, an EGF receptor family member, in asthmatic airway epithelial cells critically hinders repair after mechanical wounding

Background: Genetic and genomic data increasingly point to the airway epithelium as critical to asthma pathogenesis. Epithelial growth factor (EGF) family members play a fundamental role in epithelial differentiation, proliferation and repair. While ErbB2 mRNA, an EGF family receptor, was reported to be lower in asthma, little is understood about its functional role. Objective: To determine whether decreased ErbB2 activation in freshly isolated asthmatic human airway epithelial cells (HAECs) associated with impaired wound closure in vitro. Methods: An in vitro scratch wound model of air-liquid interface cultured and freshly isolated HAECs were compared between asthmatic and healthy HAECs in relation to ErbB2. Results: Freshly brushed asthmatic HAECs had impaired ErbB2 activation compared to healthy controls. In an in vitro scratch wound model, asthmatic HAECs showed delayed wound closure compared to healthy HAECs. Cell proliferation, assessed by [ 3 H] thymidine incorporation post wounding, as well as expression or activation of ErbB2 and CCND1 at the leading edge of the wound were lower in asthmatic compared to healthy HAECs. A selective ErbB2 tyrosine kinase inhibitor, mubritinib impaired wound closure and decreased CCND1 expression in healthy HAECs, with less impact on asthmatic cells, supporting diminished activity in asthma. Conclusion: These results implicate a primary defect in the ErbB2 pathway as constraining asthmatic epithelial repair processes. Restoration of homeostatic ErbB2 function should be considered as a novel asthma therapeutic target. Asthmatic airway epithelial cells have dysregulated wound repair, in association with lower activation of the ErbB2 pathway. Restoration of this pathway might be a novel therapeutic target, potentially restoring a disrupted airway epithelium in asthma.
Primary HPV and Molecular Cervical Cancer Screening in US Women Living With Human Immunodeficiency Virus

Background. Primary human papillomavirus (HPV) screening ( PHS ) utilizes oncogenic human papillomavirus (oncHPV) the initial cervical cancer screening method typically, if positive, additional reflex-triage (eg, HPV16/18-genotyping, Pap testing). While US guidelines support PHS usage in the general population, PHS has been little studied in women living with HIV (WLWH). value (PPV), and a 35% colposcopy referral rate (Colpo). “ PHS with reflex HPV16/18-genotyping and Pap testing ” had 84% Se, 16% PPV, 30% Colpo. PHS with only HPV16/18-genotyping had 24% Colpo. “ Concurrent oncHPV and Pap Testing” (Co-Testing) had 91% Se, 12% PPV, 40% Colpo. p16/Ki-67 immunochemistry had the highest PPV, 20%, but 13% specimen inadequacy. Conclusions. PHS with reflex HPV16/18-genotyping had fewer unnecessary colposcopies and (if confirmed) could be a potential alternative to Co-Testing in WLWH. treatment failure/disease recurrence). To minimize the possibility that sampling order might affect the results, with every other participant we alternated whether the first versus the second liquid Pap specimen collected was the one tested in assay. 20 of one vial was Pap and HPV and used to prepare a standard monolayer cervical Pap and then immediately Cobas HPV DNA HPV16/18-genotyping. residual vial (approximately was was requested HPV Screening (PHS) involves use of an oncHPV assay as the initial cervical cancer screening test without reflex HPV16/18 genotyping or Pap tests; PHS-genotype/Pap includes reflex HPV16/18 genotype and Pap testing. p16/Ki- 67 involves dual immunocytological staining for Ki67 (a proliferation marker) and p16 (a cyclin-dependent kinase inhibitor that can accumulate in HPV-positive cells when there is overexpression of the viral oncoprotein E7).
Solution structure of the inﬂuenza A virus cRNA promoter: implications for differential recognition of viral promoter structures by RNA-dependent RNA polymerase

Inﬂuenza A virus replication requires the interaction of viral RNA-dependent RNA polymerase (RdRp) with promoters in both the RNA genome (vRNA) and the full-length complementary RNA (cRNA) which serve as templates for the generation of new vRNAs. Although RdRp binds both promoters effectively, it must also discriminate between them because they serve different functional roles in the viral life cycle. Even though the inherent asymmetry between two RNA promoters is considered as a cause of the differential recognition by the RdRp, the structural basis for the ability of the RdRp to recognize the RNA promoters and discriminate effectively between them remains unsolved. Here we report the structure of the cRNA promoter of inﬂuenza A virus as determined by heteronuclear magnetic resonance spectroscopy. The terminal region is extremely unstable and does not have a rigid structure. The major groove of the internal loop is widened by the displacement of a novel A*(UU) motif toward the minor groove. These internal loop residues show distinguishable dynamic characters, with differing motional timescales for each residue. Comparison of the cRNA promoter structure with that of the vRNA promoter reveals common structural and dynamic elements in the internal loop, but also differences that provide insight into how the viral RdRp differentially recognizes the cRNA and vRNA promoters.
THE OF THE PHOSPHOLIPID IN RECONSTITUTED SARCOPLASMIC RETICULUM MEMBRANE VESICLES

The major protein component of sarcoplasmic reticulum (SR) is the calcium pump protein (CPP) comprising 90% of the membrane protein of purified SR. The CPP has all the known characteristics of the pumping molecule including energized calcium pumping when reconstituted to form membrane vesicles. The subunit molecular weight has been estimated to be 119,000 daltons. The functional pump appears to be an oligomer, possibly a trimer (1). Functional RSR vesicles were prepared containing either dioleoylphosphatidylcholine (DOPC) or dielaidoylphosphatidylcholine (DEPC). For some studies, the SR phospholipid (PL) was exchanged to 99% with a single PL. CPP accounted for >90% of the protein in these membranes and the lipid:protein molar ratio (L/P) was varied from 50 to 130 mol PL/mol CPP (2, 4). Such a high protein content, comparable to that in normal SR (L/P 110), is a favorable range to study the influence of the protein on the motional characteristics of the PL. RSR is functionally similar to normal SR in the rate of phosphoenzyme formation, phosphoenzyme hydrolysis,