Miracle-dz/UniFAR-FTUs huggingface dataset:
Histone H3 K56 Hyperacetylation Perturbs Replisomes and Causes DNA Damage

Deacetylation of histone H3 K56, regulated by the sirtuins Hst3p and Hst4p, is critical for maintenance of genomic stability. However, the physiological consequences of a lack of H3 K56 deacetylation are poorly understood. Here we show that cells lacking Hst3p and Hst4p, in which H3 K56 is constitutively hyperacetylated, exhibit hallmarks of spontaneous DNA damage, such as activation of the checkpoint kinase Rad53p and upregulation of DNA-damage inducible genes. Consistently, hst3 hst4 cells display synthetic lethality interactions with mutations that cripple genes involved in DNA replication and DNA double-strand break (DSB) repair. In most cases, synthetic lethality depends upon hyperacetylation of H3 K56 because it can be suppressed by mutation of K56 to arginine, which mimics the nonacetylated state. We also show that hst3 hst4 phenotypes can be suppressed by overexpression of the PCNA clamp loader large subunit, Rfc1p, and by inactivation of the alternative clamp loaders CTF18, RAD24, and ELG1. Loss of CTF4, encoding a replisome component involved in sister chromatid cohesion, also suppresses hst3 hst4 phenotypes. Genetic analysis suggests that CTF4 is a part of the K56 acetylation pathway that converges on and modulates replisome function. This pathway represents an important mechanism for maintenance of genomic stability and depends upon proper regulation of H3 K56 acetylation by Hst3p and Hst4p. Our data also suggest the existence of a precarious balance between Rfc1p and the other RFC complexes and that the nonreplicative forms of RFC are strongly deleterious to cells that have genomewide and constitutive H3 K56 hyperacetylation.
Does the Transtheoretical Model (TTM) Explain Exercise Behavior in a Community-Based Sample of Older Women?

Objective: To determine whether patterns of exercise adoption by older women would conform to the Transtheoretical Model (TTM) of behavior change. Methods: Participants were randomized into an exercise group (walk 30 minutes per day, 5 days per week, plus balance exercises twice per week) or attention control (health education on topics other than exercise). The intervention was conducted over 28 weeks with 1-year follow-up. Results: Participants included 272 sedentary women aged 70 and above. Exercise adoption was higher in the intervention group (83% vs. 17% among controls). After 1 year, 60% of the intervention group was in action or maintenance, compared to 16% of the control group. Self-efficacy following the intervention predicted long-term exercise adherence. Discussion: Few studies have addressed longitudinal analysis of the TTM for exercise adoption. Most constructs from the TTM were useful in explaining exercise adoption in older sedentary women.
Real-time hardware-in-the-loop simulation of electrical machine systems using FPGAs

This study focuses on the development an integrated software and hardware platform that is capable of performing real-time simulation of dynamic systems, including electrical machinery, for the purpose of hardware-in-the-loop simulation (HILS). The system to be controlled is first defined using a block diagram editor. The defined model is then compiled and downloaded onto an FPGA (“Field Programmable Gate Array”) based hardware platform, which is to interface with the controller under test and carry out the simulation in real-time. The full paper will elaborate the characteristics of this novel HILS platform.
Prediction of unsuccessful treatment in patients with severe acute asthma

Background Clinical assessment can be used to identify which patients with acute asthma are at risk of unsuccessful initial treatment. Objective To determine which elements of clinical assessment predict unsuccessful treatment, defined as needing critical care or any unplanned additional treatment. Methods We analysed data from a large multicentre trial (the 3Mg trial). Adults with severe acute asthma underwent standardised clinical assessment, including peak expiratory flow rate (PEFR), up to 2 h after initiation of treatment. Standard care was provided other than blinded random allocation to trial treatment or placebo. Patients were followed up by record review up to 30 days. Unsuccessful treatment was defined as needing (1) critical care or (2) critical care or any unplanned additional treatment within 7 days of presentation. Logistic regression was used to identify predictors and derive a prediction model for each outcome. Results Out of 1084 patients analysed, 81 (7%) received critical care and 157 (14%) received critical care or unplanned additional treatment. Baseline PEFR (p=0.017), baseline heart rate (p<0.001), other serious illness (p=0.019), PEFR change (p=0.015) and heart rate change (p<0.001) predicted need for critical care. Baseline PEFR (p=0.010), baseline heart rate (p<0.001), baseline respiratory rate (p=0.017), other serious illness (p=0.023), PEFR change (p=0.003) and heart rate change (p=0.001) predicted critical care or additional treatment. Models based on these characteristics had c-statistics of 0.77 and 0.69, respectively. Conclusions PEFR, heart rate and other serious illnesses are the best predictors of unsuccessful treatment, but models based on these variables provide modest predictive value.
Role of Methylation in the Induced and Spontaneous Expression of the Avian Endogenous Virus ev-1: DNA Structure and Gene Products

The endogenous avian provirus ev-1 is widespread in white leghorn chickens. Although it has no major structural defects, ev-1 has not been associated with any phenotype and is ordinarily expressed at a very low level. In this report, we describe a chicken embryo (Number 1836) cell culture containing both ev-1 and ev-6 which spontaneously expressed the ev-1 provirus. This culture released a high level of noninfectious virions containing a full complement of virion structural (gag) proteins but devoid of reverse transcriptase activity or antigen. These virions contained 70S RNA closely related to the genome of Rous-associated virus type 0, but identifiable as the ev-1 genome by oligonucleotide mapping. A fraction of the RNA molecules in the 70S complex were unusual in that they were polyadenylated 100 to 200 nucleotides downstream of the usual polyadenylation site. Eight sibling embryo cultures did not share this unusual phenotype with 1836, indicating that it was not inherited. However, an identical phenotype was inducible in the sibling cultures by treatment with 5-azacytidine, an inhibitor of DNA methylation, and the induced expression was stable for more than 10 generations. Analysis of chromatin structure and DNA methylation of the ev-1 provirus in 1836 cells revealed the presence (in a fraction of the proviruses) of both DNase I hypersensitive sites in the long terminal repeats and in gag and a pattern of cleavage sites for methyl-sensitive restriction endonuclease not found in a nonexpressing sibling. These results lend strong support to the role of DNA methylation in the control of gene expression. Additionally, they explain the lack of phenotype associated with ev-1 as due to a combination of its low expression and defectiveness in pol and env.
Generalized self‐navigated motion detection technique: Preliminary investigation in abdominal imaging

Patient motion remains a primary obstacle to diagnostic image quality, especially in the abdomen, despite the existence of various motion artifact reduction techniques. This work presents a self‐navigated motion detection method that can be generalized for most pulse sequences and k‐space trajectories. Motion information is extracted directly from raw MR data, requiring no additional gradient or RF pulses, no physiologic monitoring equipment, and minimal—if any—impact on scan time. Initial feasibility results with a two‐dimensional gradient echo sequence are shown in phantom studies and in vivo volunteer abdominal studies, demonstrating the sensitivity of the method to both respiratory motion and cardiovascular pulsatility. Prospectively gated images were acquired using the self‐navigated data to synchronize image acquisition with motion. These preliminary results suggest that the self‐navigated method is a promising technique for reducing motion artifacts in clinical abdominal and cardiac applications. Magn Reson Med, 2006. © 2006 Wiley‐Liss, Inc.
Bone-Related Complications and Quality of Life in Advanced Breast Cancer: Results from a Randomized Phase III Trial of Denosumab versus Zoledronic Acid

Purpose: Denosumab was shown to be superior to zoledronic acid in preventing skeletal related events (SRE) in patients with breast cancer and bone metastases in a randomized, double-blind phase III study. We evaluated further results from this study related to skeletal complications and health-related quality of life (HRQoL). Experimental Design: Patients were randomized 1:1 to receive subcutaneous denosumab 120 mg (n = 1,026) and intravenous placebo, or intravenous zoledronic acid 4 mg (n = 1,020) and subcutaneous placebo every 4 weeks. Analyses reported here include the proportion of patients with one or multiple on-study SREs, time to first radiation to bone, time to first SRE or hypercalcemia of malignancy, and change in HRQoL (functional assessment of cancer therapy–general). Results: Fewer patients receiving denosumab than zoledronic acid had an on-study SRE (31% vs. 36%, P = 0.006). The incidence of first radiation to bone was 12% (n = 123) with denosumab versus 16% (n = 162) with zoledronic acid. Denosumab prolonged the time to first radiation to bone by 26% versus zoledronic acid (HR, 0.74; 95% confidence interval [CI], 0.59–0.94, P = 0.012) and prolonged the time to first SRE or hypercalcemia of malignancy by 18% (HR, 0.82; 95% CI, 0.70–0.95; P = 0.007). Ten percent more patients had a clinically meaningful improvement in HRQoL with denosumab relative to zoledronic acid, regardless of baseline pain levels. Conclusions: Denosumab was superior to zoledronic acid in reducing bone-related complications of metastatic breast cancer and maintained HRQoL, providing an efficacious, well-tolerated treatment option for patients with bone metastases from breast cancer. Clin Cancer Res; 18(17); 4841–9. ©2012 AACR.
An empirical malaria distribution map for West Africa

The objective of this study was to produce a malaria distribution map that would constitute a useful tool for development and health planners in West Africa. The recently created continental database of malaria survey results ( MARA/ARMA 1998 ) provides the opportunity for producing empirical models and maps of malaria distribution at a regional and eventually at a continental level. This paper reports on the mapping of malaria distribution for sub‐Saharan West Africa based on these data. The strategy was to undertake a spatial statistical analysis of malaria parasite prevalence in relation to those potential bio‐physical environmental factors involved in the distribution of malaria transmission intensity which are readily available at any map location. The resulting model was then used to predict parasite prevalence for the whole of West Africa. We also produced estimates of the proportion of population of each country in the region exposed to various categories of risk to show the impact that malaria is having on individual countries. The data represent a very large sample of children in West Africa. It constitutes a first attempt to produce a malaria risk map of the West African region, based entirely on malariometric data. We anticipate that it will provide useful additional guidance to control programme managers, and that it can be refined once sufficient additional data become available.
Cytokine production in the immune response to murine gammaherpesvirus 68

Cytokine profiles were determined following intranasal infection of C57BL/6J mice with murine gammaherpesvirus 68 (MHV-68). Spleen, mediastinal, and cervical lymph node cells from infected mice produced high levels of interleukin 6 (IL-6) and gamma interferon (IFN-gamma) and lower levels of IL-2 and IL-10 following in vitro restimulation. Little or no IL-4 or IL-5 was detected. Cytokine production was generally maximal at 10 days after infection, correlating with viral clearance from the lung, although significant levels were seen as early as 3 days after administration of the virus. In vitro infection of naive splenocytes induced B-cell- dependent secretion of IL-6 and IL-10, whereas IFN-gamma and IL-2 were produced only by cells that had been primed in vivo. Depletion of B lymphocytes from primed splenocyte populations did not, however, abrogate IL-6 and IL-10 production. Highly purified immune T cells made IL-6, IL-10. and IFN-gamma following in vitro restimulation with MHV-68. Thus, IL-6 and IL-10 are components of both the acquired and the innate host response. These cytokines have potential roles in the establishment and maintenance of persistent infection.
Productivity and unemployment scale-by-scale relationship

From a macroeconomic perspective the question of productivity growth is related to the effects that productivity gains may display on the overall behavior of the economy (e.g. output, employment, wages, costs, and prices) and, furthermore, as a source of a rising standard of livings. But if economists generally agree on the long run positive effects of labor productivity on real wages and output growth, much more controversial is the issue whether productivity growth is good or bad for employment: Does productivity growth increase unemployment or does it reduce it? The empirical and theoretical results have been mixed. Empirically there is the literature on the employment and productivity differentials between Europe and the US since 1970. The early literature states a possible trade-off between employment and productivity growth (Gordon, 1997). But such empirical findings have been complicated by the recent behavior of (un)employment and productivity growth in the Europe and the US in the 90’s: The increase of productivity growth in the US in the second half of the 90’s can be shown to be associated with low and falling unemployment (Staiger et al. 2001) and with rising employment. Yet, in Europe there was the opposite tendency visible: Productivity growth seems to have reduced employment and increased unemployment. Over the business cycle the empirical evidence seems to show strong pro-cyclical comovements of employment and productivity with output (counter-cyclical for unemployment). 1 The nexus of productivity and employment is also important for the empirical study of Okun’s Law. If employment is correlated with output,
Radar Interferometric Measurements With a Planar Patch Antenna Array

A planar patch antenna array has been made for radar interferometry. The antenna array consists of 32 rectangular patches on a ceramic loaded teflon substrate. The patches are individually coupled to the microwave electronics in two orthogonal circular polarizations. The radar interferometer is intended for topographic imaging in industrial environment, in this case, a blast furnace producing hot metal for the steel and metal industry. Ordinary imaging techniques with IR or visible radiation are not possible to use due to high temperatures, scattering from dust and particles. A model of blast furnace burden material surface was measured and detected.
Long-Term Effects of Extended Unemployment Benefits for Older Workers

This paper examines the long-term effects of extended unemployment benefits that older unemployed can collect until retirement in Finland. We consider a reform that increased the age threshold of this scheme from 55 to 57 for people born in 1950 or later. Our regression discontinuity estimates show that postponing eligibility by two years increased employment over the remaining working career by seven months. Despite the corresponding reduction in unemployment, we find no evidence of significant effects on mortality or receipt of disability and sickness benefits, nor on the spouse's labor supply. We also compute the fiscal impact of the reform taking into account income taxes and social security contributions paid and benefits received. The reform increased net income transfers by 15,000 Euros over the 10-year period for an average individual.
Percutaneous balloon valvuloplasty compared with open surgical commissurotomy for mitral stenosis.

BACKGROUND Percutaneous balloon mitral valvuloplasty has been proposed as an alternative to open surgical commissurotomy for the treatment of rheumatic mitral-valve stenosis. METHODS We enrolled 60 patients with severe mitral stenosis and favorable valvular anatomy in a prospective, randomized trial comparing the two procedures. All patients underwent cardiac catheterization before the procedure and one week, six months, and three years thereafter. Hemodynamic data were analyzed by investigators who were blinded to the patients' treatment assignments. RESULTS Mitral-valve areas improved initially in both groups, from a mean (+/- SD) of 0.9 +/- 0.3 cm2 to 2.1 +/- 0.6 cm2 in the balloon-valvuloplasty group (30 patients; P < 0.01) and from 0.9 +/- 0.3 cm2 to 2.0 +/- 0.6 cm2 in the surgical group (30 patients; P < 0.001). Although improvement was maintained in both groups, mitral-valve areas were greater in the patients in the balloon-valvuloplasty group at three years (2.4 +/- 0.6 cm2, vs. 1.8 +/- 0.4 cm2 in the surgery group, P < 0.001). Restenosis occurred in three patients in the balloon-valvuloplasty group and four in the surgery group. One patient in the balloon-valvuloplasty group died of an apparent stroke after 2.5 years; four patients in the balloon-valvuloplasty group had residual atrial septal defects, and three patients (two in the balloon-valvuloplasty group and one in the surgery group) were judged to have severe mitral regurgitation. Seventy-two percent of the patients who underwent balloon valvuloplasty and 57 percent of the surgically treated patients were in New York Heart Association functional class I (i.e., they had no cardiovascular symptoms) at three years. No patient was lost to follow-up. CONCLUSIONS In the treatment of mitral stenosis, balloon valvuloplasty and open surgical commissurotomy have comparable initial results and low rates of restenosis, and both produce good functional capacity for at least three years. The potential complications associated with balloon valvuloplasty should be noted. The better hemodynamic results at three years, lower cost, and elimination of the need for thoracotomy suggest that balloon valvuloplasty should be considered for all patients with favorable mitral-valve anatomy.
Assessing the Effects of Mandated Compensation Disclosures

This paper analyzes the effects of mandated, management compensation disclosures on compensation levels. For identification, I use the introduction of the Compensation Discussion and Analysis (CD&A) in 2006, a significant expansion in the required disclosures related to compensation. The design uses the timing of the introduction date to compare manager pay at firms with and without the disclosure in a difference-in-differences analysis. I find evidence that disclosures are associated with increasing compensation. I corroborate this evidence with the partial rollback of the CD&A allowed by the Jumpstart Our Business Startups Act in 2012, again finding that the CD&A is associated with higher compensation. From cross-sectional tests, this compensation increase appears to be concentrated among managers with shorter tenure, at smaller firms, and in industries with higher variation in pay. Entrenched and powerful managers (CEOs, CFOs, and executive directors) do not have incremental pay increases with disclosures.
Chronic cough and the cough reflex in common lung diseases.

Following the experience of asthma, characterised by the presence of bronchial hyper-responsiveness, the notion has been accepted that the chronic cough of disease occurs as a result of altered sensitivity of the afferent limb of the cough reflex. Methods for testing for the 'threshold' for eliciting the cough reflex have also been borrowed from asthma care. In the main aerosols are inhaled that contain the relevant stimulus.A number of factors influence the cough response to inhaled aerosols. The distribution of the inhaled aerosol is important as certain chemically sensitive receptors are distributed in different regions of the lungs. The larynx and central airways are important but so too are the peripheral airways. The degree of bronchodilatation is also important as airway narrowing can, itself, induce coughing in man.Asthma, oesophageal reflux and rhinitis patients experience increased coughing, that is associated with increased sensitivity to inhaled capsaicin. In syndromes of chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD) increased sensitivity to coughing with capsaicin is common. This appears a specific effect of the pathogenic process of the disease. Modification of the disease process can lessen coughing and the sensitivity to capsaicin.
Self and health: factors that encourage self-esteem and functional health.

OBJECTIVE We are interested in whether functional health enhances self-esteem, as well as whether self-esteem, worker, parent, and friend identities are related to changes in functional health over a 2-year period of study. METHODS Data were collected in 1992 and 1994 from 737 older workers living in a North Carolina metropolitan area. Functional health is derived from questions asking respondents about their difficulties performing seven activities. We use Rosenberg's (1965) 10-item scale to tap self-esteem, and identities are measured with 10 adjective pairs that cover being competent, confident, and sociable as a worker, parent, and friend. RESULT Several findings are of interest. Better functional health is associated with greater self-esteem over 2 years, and self-esteem is positively related to changes in functional health. In addition, worker identity and some social background factors are associated with positive changes in self-esteem. DISCUSSION The findings suggest that good health may contribute to positive self assessments, but also the less well-studied expectation that self processes are associated with positive changes in health. Individuals may be motivated by their desire to affirm a sense of self-worth and positive identities to maintain and improve their physical health.
When Mental Inflexibility Facilitates Executive Control

Although previous research suggests that depressive ruminators tend to become stuck in a particular mind-set, this mental inflexibility may not always be disadvantageous; in some cases, it may facilitate active maintenance of a single task goal in the face of distraction. To evaluate this hypothesis, we tested 98 college students, who differed in ruminative tendencies and dysphoria levels, on two executive-control tasks. One task emphasized fast-paced shifting between goals (letter naming), and one emphasized active goal maintenance (modified Stroop). Higher ruminative tendencies predicted more errors on the goal-shifting task but fewer errors on the goal-maintenance task; these results demonstrated that ruminative tendencies have both detrimental and beneficial effects. Moreover, although ruminative tendencies and dysphoria levels were moderately correlated (r = .42), higher dysphoria levels predicted more errors on the goal-maintenance task; this finding indicates that rumination and dysphoria can have opposing effects on executive control. Overall, these results suggest that depressive rumination reflects a trait associated with more stability (goal maintenance) than flexibility (goal shifting).