Miracle-dz/UniFAR-FTUs huggingface dataset:
Topoisomerase II binds nucleosome-free DNA and acts redundantly with topoisomerase I to enhance recruitment of RNA Pol II in budding yeast

DNA topoisomerases are believed to promote transcription by removing excessive DNA supercoils produced during elongation. However, it is unclear how topoisomerases in eukaryotes are recruited and function in the transcription pathway in the context of nucleosomes. To address this problem we present high-resolution genome-wide maps of one of the major eukaryotic topoisomerases, Topoisomerase II (Top2) and nucleosomes in the budding yeast, Saccharomyces cerevisiae. Our data indicate that at promoters Top2 binds primarily to DNA that is nucleosome-free. However, although nucleosome loss enables Top2 occupancy, the opposite is not the case and the loss of Top2 has little effect on nucleosome density. We also find that Top2 is involved in transcription. Not only is Top2 enriched at highly transcribed genes, but Top2 is required redundantly with Top1 for optimal recruitment of RNA polymerase II at their promoters. These findings and the examination of candidate-activated genes suggest that nucleosome loss induced by nucleosome remodeling factors during gene activation enables Top2 binding, which in turn acts redundantly with Top1 to enhance recruitment of RNA polymerase II.
One- or Two-Stage Palate Closure in Patients with Unilateral Cleft Lip and Palate: Comparing Cephalometric and Occlusal Outcomes

Objective: To assess facial growth and dentoalveolar development in two groups of patients with complete unilateral cleft lip and palate. Primary surgical treatment differed in the timing of hard palate closure. Design: Forty-three patients with unilateral cleft lip and palate were examined. Twenty-two patients underwent early one-stage closure of the hard and soft palate cleft (mean age 23.0 ± 4.7 months); in 21 patients, the hard palate closure was delayed to 86.3 ± 39.2 months of age. Lateral cephalograms and dental casts were consecutively analyzed at four stages between 6 and 18 years of age. Results: Lateral cephalometric analysis revealed no significant intergroup differences in the sagittal and vertical craniofacial dimensions at any time. Dental cast analysis showed constriction of the upper anterior arch width at the ages of 6 and 10 years in patients with one-stage surgical palate closure, but a difference could no longer be verified at the ages of 15 and 18 years. Conclusions: The transverse distances in the upper jaw developed initially more positively in the group with delayed hard palate closure, but it became apparent later that the transverse deficiency after one-stage palate closure could be compensated for. When considering surgical treatment in general, the advantages of the delayed hard palate closure must be weighed against criteria favoring the early one-stage closure of the hard and soft palate.
Transcutaneous electrical acupoint stimulation versus ondansetron in the prevention of postoperative vomiting following pediatric tonsillectomy.

OBJECTIVES Postoperative retching and vomiting is an important cause of morbidity that may lead to patient discomfort, distress, and complications. Stimulation of acupuncture points has been shown to be effective in the prevention as well as treatment of PONV. The current treatments of choice are the 5-hydroxytryptamine type 3-antagonists, such as ondansetron. We aimed to evaluate the efficacy and side-effects of either transcutaneous electrical acupoint stimulation (TEAS) or Ondansetron compared to a control group receiving no treatment in the prevention of postoperative retching and vomiting. SUBJECT AND DESIGN: This randomized, controlled, prospective study was carried out in a group of 90 children (in three equal randomly assigned groups), aged between 4 and 12 who underwent tonsillectomy under general anesthesia. In the first group, electrical stimulation via surface electrodes on acupoints Neiguan and Shangwan was performed (20 Hz, 5 minutes). The second group received a single dose of Ondansetron (0.15 mg . kg(-1)). No treatment was given to the control group. OUTCOME MEASURES The frequency of retching and vomiting attacks and side-effects were noted on the day of surgery in the postanesthesia care unit and the day surgery care unit, on the day of surgery after discharge, and on the first day after surgery. A satisfaction scale was completed by each family. RESULTS There was a significant difference between the treatment groups and the control group in the incidence of emetic episodes occurring in the day surgery care unit and on the day after discharge (p < 0.001). In the ondansetron group, side-effects were seen in more patients than in the other groups (p < 0.001). The satisfaction scores of the parents were greater in the treatment groups than in the control group (p < 0.05). CONCLUSION Application of TEAS on sedated children is an easy, painless, reliable and effective method for the prophylaxis of postoperative retching and vomiting in pediatric tonsillectomy.
Transcriptional Regulation of Mouse Type 1 Inositol 1,4,5‐Trisphosphate Receptor Gene by NeuroD‐Related Factor

Abstract: The type 1 inositol 1,4,5‐trisphosphate receptor (IP3R1) is a Ca2+ channel protein that is expressed abundantly in the CNS, such as in the cerebellar Purkinje cells and hippocampus. We previously demonstrated that the box‐I element, which is located —334 relative to the transcription initiation site of the mouse IP3R1 gene and includes an E‐box consensus sequence, is involved in the up‐regulation of such IP3R1 gene expression. Furthermore, the previous study also indicated that some CNS‐related basic helix‐loop‐helix (bHLH) factors bind to the box‐I and activate IP3R1 gene expression. In this study, we demonstrated that one of the CNS‐related bHLH factors, neuronal differentiation factor (NeuroD)‐related factor (NDRF), specifically bound to the box‐I sequence with a ubiquitously expressed bHLH protein, E47, and activated IP3R1 gene expression. In situ hybridization of adult mouse brain revealed that IP3R1 and NDRF mRNA were co‐expressed in many subsets of neurons, highly in Purkinje cells and hippocampus and moderately in cerebral cortex, olfactory bulb, and caudate putamen. Furthermore, the spatiotemporal expression patterns of these two genes resembled one another throughout postnatal development of the mouse CNS. From these results, we suggest that NDRF is involved in the tissue‐specific regulation of IP3R1 gene expression in the CNS.
Transdisciplinarity in Research about Agrifood Systems Transitions: A Pragmatist Approach to Processes of Attachment

The much-needed transformations of agrifood systems call for novel approaches that are able to bring together a diversity of actors’ and institutions’ knowledge and visions. While within the literature about participatory research and transdisciplinarity, many articles have discussed the issue of actor involvement, few have addressed it regarding agrifood system transitions, which are the focus of this paper. Inspired by recent work suggesting a pragmatist approach to stakeholder involvement and collective processes of problem framing and solving, this study (based on a reflexive analysis of six different projects involving different approaches to stakeholder involvement) developed an actor-oriented approach focused on what the motivations to enroll actors and for them to be enrolled are, and on the analysis of the diverse visions and controversies at play. The main outcome of this analysis is that a key issue regarding stakeholder involvement appears to be whether the diverse stakeholders and researchers involved share the sense of being part of a “community of fate” that makes them feel individually “affected” but also collectively “attached” to a shared problem and possibly to a shared future. This is not fixed and stable but can be reinforced through the research–action process itself, which should produce this collective attachment.
How much do the tax benefits of debt add to firm value? Evidence from spanish listed firms

The potentially important impact of taxation on corporate financing decisions is widely recognized despite the fact that the empirical evidence is far from conclusive. In this study, we assess the debt tax benefits of Spanish listed firms throughout the period 2007-2013. Specifically, using a simulation approach, we found the capitalized value of gross interest deductions amounts to approximately 6.4% of firms’ market value, while the net debt benefit (of personal taxes) is estimated at 2.1%, in contrast to the traditional 11.4% (i.e.marginal tax rate times debt). Conversely, the panel data regression approach reveals a 13.6% (34.2%) debt tax shield in terms of firm (debt) value. This evidence supports the view that taxes influence corporate decision-making and that debt makes a reasonable contribution to firm value.
Immunodiagnosis of alveolar echinococcosis by enzyme-linked immunosorbent assay using a partially purified Em18/16 enriched fraction

An improved enzyme-linked immunosorbent assay (ELISA) system using partially purified Eml8/16 enriched fraction (PP-Em18/16) prepared by isoelectric focusing was evaluated for serodiagnosis of alveolar echinococcosis (AE). The PP-Em18/16-ELISA was compared with Em2plus-ELISA by using sera from AE and cystic echinococcosis (CE) patients in China, where both AE and CE are endemic; sera from CE patients in Australia, where only CE exists; and sera from patients with cysticercosis, paragonimiasis, or sparganosis in Korea, where no indigenous AE or CE exists. We used Em2plus-ELISA as a standard ELISA and found 24.6% (17 of 69 specimens) cross-reactivity with sera from CE. Furthermore, some of the sera from paragonimiasis, sparganosis, and cysticercosis patients were also cross-reactive in the Em2plus-ELISA. When we tested for similar cross-reactivity in the same sera from CE patients by PP-Em18/16-ELISA (23.2%, 16 of 69), it became evident that the specificity of the PP-Em18/16-ELISA was better than that of the Em2plus-ELISA, since no sera from patients with the examined parasitic diseases except CE showed cross-reactivity. Some CE patients from China showed exceptionally high levels of antibody in comparison with those of CE patients from Australia, where no AE occurs. It is speculated that these patients with strongly positive cases of CE from China may have been exposed to both species of Echinococcus.
Neonatal corticosterone programs for thrifty phenotype adult diabetic manifestations and oxidative stress: countering effect of melatonin as a deprogrammer

Objective: The present study assesses the thrifty phenotype response of neonatal corticosterone programming to a diabetogenic challenge in adult rats and the role of melatonin as a deprogrammer. Methods: Neonates of both sexes, born of healthy male and female rats maintained under standard conditions of temperature and light, were separated and, equal number of pups was assigned to lactating mothers. Pups treated with either saline or corticosterone or, a combination of corticosterone and melatonin from postnatal day (PND) 2 to PND 14 and, at 120 days of age, six animals from each treatment group were rendered diabetic by alloxanization. Various serum and tissue parameters pertaining to glycaemic regulation, dyslipidemia, hepatic and renal distress and oxidative stress were analysed in adult rats of all groups. Results: The results indicate compromised feed efficiency, hyperglycaemia, hypoinsulinemia, decreased glycogen content, elevated serum and tissue lipids and serum markers of hepatic and renal stress, together with increased lipid peroxidation, and decreased levels of non-enzymatic and enzymatic antioxidants in corticosterone programmed diabetic animals than in the non-programmed diabetic rats. However, treatment with melatonin simultaneously prevented to a significant extent the alterations in carbohydrate and lipid metabolism and oxidative stress. Conclusions: Melatonin is a potent deprogrammer of neonatal corticosterone programming effects and the adult thrifty phenotype alteration to a diabetogenic challenge.
Elucidation of the chemistry of enzyme-bound thiamin diphosphate prior to substrate binding: defining internal equilibria among tautomeric and ionization states.

Both solution and crystallographic studies suggest that the 4'-aminopyrimidine ring of the thiamin diphosphate coenzyme participates in catalysis, likely as an intramolecular general acid-base catalyst via the unusual 1',4'-iminopyrimidine tautomer. It is indeed uncommon for a coenzyme to be identified in its rare tautomeric form on its reaction pathways, yet this has been possible with thiamin diphosphate, in some cases even in the absence of substrate [Nemeria, N. , Chakraborty, S. , Baykal, A. , Korotchkina, L. , Patel, M. S. , and Jordan, F. (2007) Proc. Natl. Acad. Sci. U.S.A. 104, 78-82. ]. The ability to detect both the aminopyrimidine and iminopyrimidine tautomeric forms of thiamin diphosphate on enzymes has enabled us to assign the predominant tautomeric form present in individual intermediates on the pathway. Herein, we report the pH dependence of these tautomeric forms providing the first data for the internal thermodynamic equilibria on thiamin diphosphate enzymes for the various ionization and tautomeric forms of this coenzyme on four enzymes: benzaldehyde lyase, benzoylformate decarboxylase, pyruvate oxidase, and the E1 component of the human pyruvate dehydrogenase multienzyme complex. Evidence is provided for an important function of the enzyme environment in altering both the ionization and tautomeric equilibria on the coenzyme even prior to addition of substrate. The pKa for the 4'-aminopyrimidinium moiety coincides with the pH for optimum activity thereby ensuring that all ionization states and tautomeric states are accessible during the catalytic cycle. The dramatic influence of the protein on the internal equilibria also points to conditions under which the long-elusive ylide intermediate could be stabilized.
The inter-relationship between formal and informal care: a study in France and Israel

ABSTRACT This study examined whether formal care services delivered to frail older people's homes in France and Israel substitute for or complement informal support. The two countries have comparable family welfare systems but many historical, cultural and religious differences. Data for the respondents aged 75 or more years at the first wave of the Survey of Health, Ageing and Retirement in Europe (SHARE) were analysed. Regressions were examined of three patterns of care from outside the household: informal support only, formal support only and both formal and informal care, with the predictor variables including whether informal help was provided by a family member living in the household. The results revealed that about one-half of the respondents received no help at all (France 51%, Israel 55%), about one-tenth received care from a household member (France 8%, Israel 10%), and one-third were helped by informal carers from outside the household (France 34%, Israel 33%). More French respondents (35%) received formal care services at home than Israelis (27%). Most predictors of the care patterns were similar in the two countries. The analysis showed that complementarity is a common outcome of the co-existence of formal and informal care, and that mixed provision occurs more frequently in situations of greater need. It is also shown that spouse care-givers had less formal home-care supports than either co-resident children or other family care-givers. Even so, spouses, children and other family care-givers all had considerable support from formal home-delivered care.
Organized Labor’s Check on Rising Economic Inequality in the U.S. States

Recent demonstrations of growing economic inequality in the United States raise normative concerns about the political representation of all but the very wealthiest citizens. Building on existing cross-national work on the roles of unions in welfare states, I provide evidence that organized labor, as a political institution, limits unequal income distributions in the U.S. states. The states are useful to our understanding of labor’s influence on inequality as states differ in their acceptance of labor unions, base levels of inequality, political preferences, industries, and levels of development but are all nested within a single overarching national framework. Over the 39-year period examined, states where unions maintain more members remain more equal within the labor market and after redistribution via government transfer. These effects persist after accounting for state-level policy, demography, and economic conditions. However, states where union membership has the largest influence on inequality have also seen growing attempts to reduce unionization rates. Overall, I find that unions are still able to limit the growth of economic inequality in spite of declining levels of union membership.
Integrating routine lactation consultant support into a pediatric practice.

BACKGROUND Although research shows that healthcare professionals' support improves breastfeeding duration, many physicians do not believe they have adequate time to address breastfeeding concerns during office visits. This study evaluated the impact of a pediatric practice's postnatal lactation consultant intervention. To improve breastfeeding support, the study practice changed policy and began using a lactation consultant overseen by a physician, to conduct the initial postpartum office visit for all breastfeeding infants. METHODS A retrospective chart review was performed on consecutive newborns before (n = 166) and after (n = 184) implementation of the program. Feeding method was assessed at each well child visit during the infant's first 9 months. χ² and logistic growth curve analyses were used to test the association between implementation status and non-formula feeding (NFF). RESULTS Mothers and infants in 2007 and 2009 were similar with regard to type of insurance, parity, gestational age, multiple births, and cesarean sections. Overall, NFF improved after program implementation (odds ratio = 1.12, 95% confidence interval 1.02-1.23). In 2009, NFF rates at 2 months, 4 months, 6 months, and 9 months were greater than 2007 rates by 10%, 15%, 11%, and 9%, respectively. Logistic growth curve analysis indicated the difference across these time points was significant between 2007 and 2009. CONCLUSION A routine post-discharge outpatient lactation visit coordinated within a primary care practice improved breastfeeding initiation and intensity. This effect was sustained for 9 months.
Nocturnal leg cramps

A prospective, double-blind, placebo-controlled crossover study of the use of quinine for nocturnal leg cramps was carried out in 8 elderly volunteer patients. The patients were randomly assigned to receive either placebo or 200 mg of quinine sulfate by mouth at bedtime. After 4 weeks of treatment and after a one-week washout period, the group taking quinine switched to placebo and vice versa for another 4 weeks. The differences in the number, duration, and severity of cramps and the side effects were compared. All of the patients had fewer cramps and decreased severity and duration of attacks while receiving quinine. Mild side effects developed in only 2 patients, and these subsided without treatment or discontinuing the medication. We conclude that quinine was effective in relieving nocturnal leg cramps in a selected group of elderly patients.
Advancing voluntary chemical governance? The case of the Swedish textile industry dialogue

Voluntary environmental governance is a widely used policy approach that has been criticized for its lack of effectiveness. This raises fundamental questions about how to design processes that can advance voluntary programmes in a way that makes them more successful. In this paper, we analyse a government-initiated dialogue process to phase out hazardous chemicals through voluntary action by the Swedish textile industry. The analysis shows that information transfer primarily motivated business participation, while consumer pressure, regulatory threats and traditions of government–business cooperation played minor roles. The institutional design of the dialogue ensured close interaction within a homogeneous group, but collective actions were limited by disagreement about the problems to be addressed, prior unilateral environmental commitments by leading companies, and ambivalent engagement. This case provides valuable insights into the effect of institutional design on the actual interplay between business and government and its effects on voluntary governance.
The Fate of AAA Patients Referred Electively to Vascular Surgical Unit

Background: The ideal treatment of abdominal aortic aneurysms (AAA) is to operate aneurysms likely to rupture, without exposing other cases to major surgery. The purpose here was to analyse retrospectively the management of AAA in a well-defined geographical region in the 1990's. Methods: 194 new vascular surgical outpatient consultations due to AAA were done to the regional vascular centre during the years 1990, 1992, 1994, 1996 and 1998. Data were collected from case records. Statistics Finland provided causes and dates of death. Results: The mean observed annual AAA incidence was 9.0 per 100 000 inhabitants and it rose significantly (33.3 %) during the study period. The duration of follow-up varied between 0 and 129 months. The 5/8-year cumulative mortality was 37.3/50.7 %. The most common causes of death were AAA-related (31.7 %), cardiac (29.1 %) or malignancy (19.0 %). Twenty-five patients with small AAA were referred to primary health care sector for further follow-up. There were no RAAA (ruptured AAA) deaths in this group. The cumulative 5/8-year mortality was 43.2/49.9 %. One hundred patients underwent an elective aneurysm repair with in-hospital mortality of 7.0 %. The cumulative 5/8-year mortality was 23.7/35.4 %. Twelve patients refused elective treatment. The cumulative 5/8-year mortality was 45.1/63.4 % and 5/7 deaths were due to RAAA. Twenty-three patients were unfit for elective repair. The cumulative 5/8-year mortality was 87.0 %/100 % and 5/20 deaths were caused by RAAA. The cumulative 5/8-year RAAA-rate in the patients with AAA more than 5.0 cm in diameter and outside elective aneurysm-repair (n = 23) was 51.9 %/100.0 %. Conclusion: The observed incidence of AAA increased during the 1990's. Half of the patients underwent an elective procedure. Patients unfit for surgery died mainly for other reasons than RAAA. Most patients with AAA over 5.5 cm not subjected to elective procedure, died of rupture.
Antibodies to type II collagen in early rheumatoid arthritis. Correlation with disease progression.

OBJECTIVE To establish that frequencies and levels of IgG antibodies to type II collagen are higher in early rheumatoid arthritis (RA), and to correlate these results with disease activity. METHODS Forty-four patients were characterized as having early RA. Patient sera obtained at initial presentation and at 12 months were tested by enzyme-linked immunosorbent assay for IgG antibodies to native and denatured type II collagen. RESULTS IgG antibodies to native and denatured type II collagen were detected at initial presentation in 27% and 82% of patients, respectively, and after 12 months in 14% and 50%, respectively. The presence of antibodies to native collagen was associated with activity of RA and severity of symptoms, and loss of antibodies at 12 months was associated with initially erosive RA and the DRB1 disease susceptibility motif. CONCLUSION Levels of serum IgG antibodies to collagen in RA decrease over time and, therefore, are not attributable simply to cartilage destruction. The presence of early positivity for these antibodies, together with the RA susceptibility motif, appears to be predictive of rapidly progressive RA.