Miracle-dz/UniFAR-FTUs huggingface dataset:
Endogenous nitric oxide attenuates neutrally mediated cutaneous vasoconstriction

Cutaneous vasoconstrictor responsiveness may be impaired by substance(s) directly or indirectly responsible for cutaneous active vasodilatation. In this study, we tested the hypothesis that endogenous nitric oxide (NO) attenuates the reduction in cutaneous vascular conductance (CVC) during an orthostatic challenge combined with whole‐body heating, as well as during whole‐body cooling. In protocol 1, healthy subjects were pretreated with an intradermal injection of botulinum toxin A (BTX) to block the release of neurotransmitters from nerves responsible for cutaneous active vasodilatation. On the experimental day, a microdialysis probe was placed at the BTX‐treated site as well as at two adjacent untreated sites. NG‐nitro‐l‐arginine methyl ester (l‐NAME, 10 mm) was perfused through the probe placed at the BTX‐treated site and at one untreated site. After confirmation of the absence of cutaneous vasodilatation at the BTX site during whole‐body heating, adenosine was infused through the microdialysis probe at this site to increase skin blood flow to a level similar to that at the untreated site. Subsequently, 30 and 40 mmHg lower‐body negative pressures (LBNPs) were applied. The reduction in CVC to LBNP was greatest at the BTX‐treated site (15.0 ± 2.4% of the maximum level (% max)), followed by the l‐NAME‐treated site (11.3 ± 2.6% max), and then the untreated site (3.8 ± 3.0% max; P < 0.05 for all comparisons). In protocol 2, two microdialysis membranes were inserted in the dermal space of one forearm. Adenosine alone was infused at one site while the other site received adenosine and l‐NAME. The reduction in CVC in response to whole‐body cooling was significantly greater at the l‐NAME‐treated site than at the adjacent adenosine alone site. These results suggest that endogenous NO is capable of attenuating cutaneous vasoconstrictor responsiveness.
A heparin-binding growth factor secreted by macrophage-like cells that is related to EGF

Macrophage-like U-937 cells secrete a 22-kilodalton heparin-binding growth factor that is mitogenic for BALB-3T3 fibroblasts and smooth muscle cells, but not endothelial cells. The amino acid sequence predicted from complementary DNA clones indicates that the mitogen is a new member of the epidermal growth factor (EGF) family. This heparin-binding EGF-like growth factor (HB-EGF) binds to EGF receptors on A-431 epidermoid carcinoma cells and smooth muscle cells, but is a far more potent mitogen for smooth muscle cells than is EGF. HB-EGF is also expressed in cultured human macrophages and may be involved in macrophage-mediated cellular proliferation.
Lamb-wave microdevices fabricated on monolithic single crystal silicon wafers

Reliable and inexpensive microdevices that can be used in physical, chemical, biological, and environmental applications are in great demand. Lamb-wave (LW) ultrasonic devices have been shown to be extremely useful for applications in liquid environments. Working LW devices have been fabricated in this investigation on monolithic single crystal membranes using well-established integrated-circuit technology. The detailed fabrication procedure, photoacoustic testing of the piezoelectric material film, and a demonstration of device performance are presented in this paper. In practice, device performance was very sensitive to the surface quality of the membrane structure. This process presents the possibility for further size reduction, increased integration, and large-scale production.
Contribution of the Collagen Adhesin Acm to Pathogenesis of Enterococcus faecium in Experimental Endocarditis

ABSTRACT Enterococcus faecium is a multidrug-resistant opportunist causing difficult-to-treat nosocomial infections, including endocarditis, but there are no reports experimentally demonstrating E. faecium virulence determinants. Our previous studies showed that some clinical E. faecium isolates produce a cell wall-anchored collagen adhesin, Acm, and that an isogenic acm deletion mutant of the endocarditis-derived strain TX0082 lost collagen adherence. In this study, we show with a rat endocarditis model that TX0082 Δacm::cat is highly attenuated versus wild-type TX0082, both in established (72 h) vegetations (P < 0.0001) and for valve colonization 1 and 3 hours after infection (P ≤ 0.0002), making Acm the first factor shown to be important for E. faecium pathogenesis. In contrast, no mortality differences were observed in a mouse peritonitis model. While 5 of 17 endocarditis isolates were Acm nonproducers and failed to adhere to collagen in vitro, all had an intact, highly conserved acm locus. Highly reduced acm mRNA levels (≥50-fold reduction relative to an Acm producer) were found in three of these five nonadherent isolates, including the sequenced strain TX0016, by quantitative reverse transcription-PCR, indicating that acm transcription is downregulated in vitro in these isolates. However, examination of TX0016 cells obtained directly from infected rat vegetations by flow cytometry showed that Acm was present on 40% of cells grown during infection. Finally, we demonstrated a significant reduction in E. faecium collagen adherence by affinity-purified anti-Acm antibodies from E. faecium endocarditis patient sera, suggesting that Acm may be a potential immunotarget for strategies to control this emerging pathogen.
Cytokinesis breaks dicentric chromosomes preferentially at pericentromeric regions and telomere fusions

Dicentric chromosomes are unstable products of erroneous DNA repair events that can lead to further genome rearrangements and extended gene copy number variations. Lopez et al. find that dicentrics without internal telomere sequences preferentially break at pericentromeric regions. In all cases, cleavage does not occur in anaphase but instead requires cytokinesis. Dicentrics cause the spindle pole bodies and centromeres to relocate to the bud neck during cytokinesis, explaining how cytokinesis can sever dicentrics near centromeres.
Neutrophil Isolation Protocol

Neutrophil polymorphonuclear granulocytes (PMN) are the most abundant leukocytes in humans and among the first cells to arrive on the site of inflammatory immune response. Due to their key role in inflammation, neutrophil functions such as locomotion, cytokine production, phagocytosis, and tumor cell combat are extensively studied. To characterize the specific functions of neutrophils, a clean, fast, and reliable method of separating them from other blood cells is desirable for in vitro studies, especially since neutrophils are short-lived and should be used within 2-4 hours of collection. Here, we demonstrate a standard density gradient separation method to isolate human neutrophils from whole blood using commercially available separation media that is a mixture of sodium metrizoate and Dextran 500. The procedure consists of layering whole blood over the density gradient medium, centrifugation, separation of neutrophil layer, and lysis of residual erythrocytes. Cells are then washed, counted, and resuspended in buffer to desired concentration. When performed correctly, this method has been shown to yield samples of >95% neutrophils with >95% viability.
Effect of trihalomethane exposure on fetal development

Aims: To examine the effect of trimester specific and pregnancy average total trihalomethane (TTHM) exposure on infant birth weight, low birth weight, and intrauterine growth retardation in term births, as well as gestational age and preterm delivery in all births. Methods: Cross sectional analysis of 56 513 singleton infants born to residents of Massachusetts during 1990. City specific aggregate data were used to estimate maternal exposure to TTHM concentration; individual maternal information was used to adjust for confounding. Results: Increased pregnancy average and second trimester TTHM exposure were associated with small for gestational age and reductions in birth weight after adjusting for potential confounding variables. Compared to ≤60 μg/l, pregnancy average TTHM exposure over 80 μg/l was associated with a 32 g reduction in birth weight. There was a 23 g reduction in birth weight in infants born to mothers exposed to greater than 80 μg/l TTHM during the second trimester. For each 20 μg/l increase in TTHM, the estimated reduction in birth was 2.8 g for pregnancy average exposure and 2.6 g for second trimester exposure. An increased risk of small for gestational age births was found for pregnancy average (odds ratio (OR) 1.14; 95% CI 1.02 to 1.26) and second trimester (OR 1.13, 95% CI 1.03 to 1.24) TTHM levels greater than 80 μg/l. There was no evidence of an association between preterm delivery and increased TTHM levels, but there were slight increases in gestational duration associated with TTHM concentrations. Conclusions: Maternal exposure to THMs may be associated with fetal growth retardation. Our findings are consistent with most previous work, although we generally found smaller effects of TTHMs on low birth weight and intrauterine growth retardation.
On cognitive radio networks with opportunistic power control strategies in fading channels

In this paper, we consider a cognitive radio system in fading wireless channels and propose an opportunistic power control strategy for the cognitive users, which serves as an alternative way to protect the primary user's transmission and to realize spectrum sharing between the primary user and the cognitive users. The key feature of the proposed strategy is that, via opportunistically adapting its transmit power, the cognitive user can maximize its achievable transmission rate without degrading the outage probability of the primary user. If compared with the existing cognitive protocols, which usually try to keep the instantaneous rate of the primary user unchanged, our strategy relieves the cognitive users from the burden of detecting and relaying the message of the primary user and relaxes the system synchronization requirements. The achievable rate of a cognitive user under the proposed power control strategy is analyzed and simulated, taking into account the impact of imperfect channel estimation. A modified power control strategy is also proposed to reduce the sensitivity of our strategy to the estimation errors. Its effectiveness is verified by the simulations.
Evolution of distinct EGF domains with specific functions

EGF domains are extracellular protein modules cross‐linked by three intradomain disulfides. Past studies suggest the existence of two types of EGF domain with three‐disulfides, human EGF‐like (hEGF) domains and complement C1r‐like (cEGF) domains, but to date no functional information has been related to the two different types, and they are not differentiated in sequence or structure databases. We have developed new sequence patterns based on the different C‐termini to search specifically for the two types of EGF domains in sequence databases. The exhibited sensitivity and specificity of the new pattern‐based method represents a significant advancement over the currently available sequence detection techniques. We re‐annotated EGF sequences in the latest release of Swiss‐Prot looking for functional relationships that might correlate with EGF type. We show that important post‐translational modifications of three‐disulfide EGFs, including unusual forms of glycosylation and post‐translational proteolytic processing, are dependent on EGF subtype. For example, EGF domains that are shed from the cell surface and mediate intercellular signaling are all hEGFs, as are all human EGF receptor family ligands. Additional experimental data suggest that functional specialization has accompanied subtype divergence. Based on our structural analysis of EGF domains with three‐disulfide bonds and comparison to laminin and integrin‐like EGF domains with an additional inter‐domain disulfide, we propose that these hEGF and cEGF domains may have arisen from a four‐disulfide ancestor by selective loss of different cysteine residues.
Gender differences in health-related quality of life following ST-elevation myocardial infarction: women and men do not benefit from primary percutaneous coronary intervention to the same degree

Background There is limited evidence whether women benefit to the same degree as men from treatment of myocardial infarction with percutaneous coronary intervention (PCI) when compared to fibrinolysis. This study compares health-related quality of life (HRQoL) outcomes for men and women randomized to primary PCI and fibrinolysis. Design A questionnaire-based study in 1351 patients with ST-elevation myocardial infarction (STEMI), assessed at 1 and 12 months after the infarction. Methods HRQoL was measured with the Medical Outcomes Study Short Form (SF-36), the Hospital Anxiety and Depression Scale (HADS), Rose's angina and dyspnoea questionnaire and global QoL questions. Results Women had a worse score than men on all endpoints at 1 month and at several endpoints at 12 months. In analyses of gender differences in benefits of PCI 1 month after the STEMI, significant gender differences were found in the SF-36 mental component summary scale, with men having better scores after primary PCI and women having better scores after fibrinolysis (P = 0.03). At 12 months, similar gender differences in treatment benefit were found in the SF-36 scales for general health (P = 0.01), mental health (P < 0.01), and the mental component summary scale (P =0.01), as well as in the scales for anxiety (P = 0.04), depression (P = 0.02), and global quality of life (P < 0.01); men had better scores after primary-PCI and women had better scores after fibrinolysis. Conclusion Compared to fibrinolysis treatment in patients with ST-elevation myocardial infarction, women do not seem to benefit from primary PCI to the same degree as men. Since previous studies have found no gender differences in clinical outcomes, this result may be specific to HRQoL. Eur J Cardiovasc Prev Rehabil 14: 37-43 © 2007 The European Society of Cardiology
Dietary lutein, zeaxanthin, and fats and the progression of age-related macular degeneration.

BACKGROUND To estimate the effect of dietary intake of lutein and zeaxanthin (L/Z) and fats on the progression of age-related macular degeneration (AMD). METHODS Two hundred and fifty-four subjects identified with early age-related macular degeneration (AMD) were re-examined to determine 7-year AMD progression. Intakes of L/Z and fatty acids were estimated from food frequency questionnaires. Progression was defined by 3 different definitions, 2 quantitative and 1 qualitative, which varied in the stringency of the change required for the AMD to be deemed to have progressed. Covariates included age, smoking, AMD family history, source study, and follow-up duration. RESULTS Energy-adjusted L/Z intake as a continuous variable was associated with AMD progression in the worse affected eye when defined by the most stringent criterion (odds ratio [OR] = 2.65, 95% confidence interval [CI] 1.13-6.22, p = 0.02). Similar associations were observed for the 2 other progression definitions (p = 0.18 and p = 0.13). Energy-adjusted omega-3 fatty acid intake modelled as a quintile median was associated with AMD progression only in the side-by-side assessment (OR = 2.56, 95% CI 1.11-5.91, p = 0.03), with borderline significance in the other 2 definitions (p = 0.05 and p = 0.08). No association of AMD progression was observed with the intake of either total fat or other subgroups: saturated, polyunsaturated, or monounsaturated fats; trans fatty acids; or omega-6 fatty acids. INTERPRETATION The findings of the study are counterintuitive, suggesting that increased intakes of dietary L/Z and omega-3 fatty acids are associated with progression of AMD. These results may indicate that too much of a good thing might be harmful. It is possible that in this study participants adopted a more healthy diet, having been aware of their AMD status at the beginning of the study. This healthy diet was then reflected in the dietary questionnaire completed at the end of study. However, this explanation may not adequately explain why those whose AMD had progressed, on the basis of fundus signs and not symptoms such as visual acuity decline, adopted a healthier lifestyle more aggressively than those without progression.
Outcomes of diabetics receiving bare‐metal stents versus drug‐eluting stents

Objectives: We sought to determine if differences existed in in‐hospital outcomes, long‐term rates of target vessel revascularization (TVR), and/or long‐term mortality trends between patients with diabetes mellitus undergoing percutaneous coronary intervention (PCI) with either a drug‐eluting stent(s) (DES) or a bare metal stent(s) (BMS). Background: Short‐ and long‐term clinical outcomes of patients with diabetes mellitus undergoing PCI with DES versus BMS remain inconsistent between randomized‐controlled trials (RCTs) and observational studies. Methods: Data were collected prospectively on diabetics undergoing PCI with either DES or BMS from January 2000 to June 2008. Demographic information, medical histories, in‐hospital outcomes, and long‐term TVR and mortality trends were obtained for all patients. Results: A total of 1,319 patients were included in the study. Diabetics receiving DES had a significant reduction in index admission MACE compared to diabetics receiving BMS. Using multivariable adjustment, after a mean follow‐up of 2.5 years (maximum 5 years), diabetics who received DES had a 38% decreased risk of TVR compared to diabetics with BMS [HR 0.62 (95% CI: 0.43–0.90)]; diabetics with DES had an insignificant adjusted improvement in long‐term survival compared to diabetics with BMS [HR 0.72 (95% CI: 0.52–1.00)]. These long‐term survival and TVR rates were confirmed using propensity scoring. Conclusions: The use of DES when compared with BMS among diabetics undergoing PCI is associated with significant improvement in long‐term TVR, with an insignificant similar trend in all‐cause mortality. The long‐term results of this observational study are consistent with prior RCTs after adjusting for confounding variables. © 2010 Wiley‐Liss, Inc.
BUILDING PARLIAMENT: 50 YEARS OF EUROPEAN PARLIAMENT HISTORY

Th ere is hardly a political system in the modern world that does not have a parliamentary assembly in its institutional ‘toolkit’. Even autocratic or totalitarian systems have found a way of creating the illusion of popular expression, albeit tamed and subjugated.Th e parliamentary institution is not in itself a suffi cient condition for granting a democratic licence. Yet the existence of a parliament is a necessary condition of what we have defi ned since the English, American and French Revolutions as ‘democracy’. Since the start of European integration, the history of the European Parliament has fallen between these two extremes. Europe was not initially created with democracy in mind. Yet Europe today is realistic only if it espouses the canons of democracy. In other words, political realism in our era means building a new utopia, that of a supranational or post-national democracy, while for two centuries the DNA of democracy has been its realisation within the nation-state. Yves MenyPresident of the European University Institute, Florence
The Unintended Consequences of the Frequency of PCAOB Inspection

After more than 50 years of self-regulation of the US auditing profession, the Sarbanes-Oxley Act of 2002 (SOX) created the Public Company Accounting Oversight Board (PCAOB) as a quasi-governmental entity with statutory authority to inspect accounting firms that audit public clients. The frequency of this inspection is annual or triennial, based upon the number of public clients the firm audits. We examine the effects of these two levels of inspection frequency on financial reporting quality and audit fees for clients of small and midsize public accounting firms. Our findings provide evidence of significantly higher audit quality and audit fees for clients of annually inspected firms relative to clients of triennially inspected firms. These findings are robust to auditor-client alignment analyses, propensity score matching, time-series analyses, examination of firms that have changed from triennial to annual inspection, and particular examination of firms with inspection deficiencies. Overall, our study suggests that the two-tier frequency system of PCAOB inspection may have also resulted in two-tier audit quality and audit fee systems for small and midsize public accounting firms, with more frequent inspection leading to more rigorous and informed auditor decisions. We discuss the implications of our results for the Board and the profession at large.
Follow-up of adult celiac patients: which noninvasive test reflects mucosal status most reliably?1.

UNLABELLED SPECIFIC AUTHOR CONTRIBUTIONS: Andreas Vécsei, MD, and Ulrike Graf wrote the manuscript. All authors contributed to study design, data collection and analysis, and approved the final draft for submission. The corresponding author declares that the manuscript is submitted on behalf of all authors. BACKGROUND AND STUDY AIMS The best mode of follow-up in celiac disease has not yet been established. The intention of this study was to clarify which noninvasive follow-up investigation - serological tests or intestinal permeability test (IPT) - correlates best with histology and whether the interval between diagnosis and follow-up affects the accuracy of these tests. PATIENTS AND METHODS Data from adult patients with celiac disease (diagnosed between December 1989 and July 2006) followed up with biopsy, IPT, and serological tests [IgG anti-gliadin antibodies (AGA-IgG), AGA-IgA, and endomysial antibodies (EMA)] were retrieved from a computerized database. Results of noninvasive tests were compared with the persistence of villous atrophy on biopsy. Patients were divided into groups A, which comprised patients followed up within 2 years after diagnosis, and B, comprising patients followed up later than 2 years. RESULTS Forty-seven patients were evaluable. The lactulose/mannitol (L/M) ratio had a sensitivity of 85 % and a specificity of 46.2 % for mucosal atrophy, whereas saccharose excretion showed a sensitivity of 60 % and a specificity of 52.6 %. The sensitivities of AGA-IgA and AGA-IgG were 15 % and 20 %, respectively, while specificity was 100 % for both. Validity of AGA was limited due to low number of positive results. EMA assay was 50 % sensitive and 77.8 % specific. In group A (n = 23) L/M ratio performed best in terms of sensitivity (88.9 %), whereas EMA achieved a higher specificity (71.4 %). In group B, the sensitivity of the L/M ratio decreased to 85.7 %, while the specificity of EMA increased to 91.7 %. CONCLUSIONS In this study, none of the noninvasive tests was an accurate substitute for follow-up biopsy in detecting severe mucosal damage.