Miracle-dz/UniFAR-FTUs huggingface dataset:
Integrative analysis of copy number and gene expression data suggests novel pathogenetic mechanisms in primary myelofibrosis

Primary myelofibrosis (PMF) is a Myeloproliferative Neoplasm (MPN) characterized by megakaryocyte hyperplasia, progressive bone marrow fibrosis, extramedullary hematopoiesis and transformation to Acute Myeloid Leukemia (AML). A number of phenotypic driver (JAK2, CALR, MPL) and additional subclonal mutations have been described in PMF, pointing to a complex genomic landscape. To discover novel genomic lesions that can contribute to disease phenotype and/or development, gene expression and copy number signals were integrated and several genomic abnormalities leading to a concordant alteration in gene expression levels were identified. In particular, copy number gain in the polyamine oxidase (PAOX) gene locus was accompanied by a coordinated transcriptional up‐regulation in PMF patients. PAOX inhibition resulted in rapid cell death of PMF progenitor cells, while sparing normal cells, suggesting that PAOX inhibition could represent a therapeutic strategy to selectively target PMF cells without affecting normal hematopoietic cells' survival. Moreover, copy number loss in the chromatin modifier HMGXB4 gene correlates with a concomitant transcriptional down‐regulation in PMF patients. Interestingly, silencing of HMGXB4 induces megakaryocyte differentiation, while inhibiting erythroid development, in human hematopoietic stem/progenitor cells. These results highlight a previously un‐reported, yet potentially interesting role of HMGXB4 in the hematopoietic system and suggest that genomic and transcriptional imbalances of HMGXB4 could contribute to the aberrant expansion of the megakaryocytic lineage that characterizes PMF patients.
Institutional Investors on Boards and Audit Committees and Their Effects on Financial Reporting Quality

Manuscript Type. Empirical. Research Question/Issue. This study examines how the presence of representatives of institutional investors as directors on boards or on audit committees enhances financial reporting quality, reducing the probability that the firm receives qualified audit reports. We focus on directors who maintain business relations with the firm on whose board or committee they sit (pressure‐sensitive directors). We also investigate the specific role of bank directors and examine their effects on financial reporting quality when they act as shareholders and directors. Research Findings/Insights. Our results suggest that institutional directors are effective monitors, which leads to higher quality financial reporting and, therefore, a lower likelihood that the firm receives a qualified audit report. Consistent with the relevant role of business relations with the firm, we find that directors appointed to both boards and audit committees by pressure‐sensitive investors have a larger effect on financial reporting quality as it is more likely that the auditor issues an unqualified audit opinion. Nevertheless, when analyzed separately, only savings bank representatives on the board increase financial reporting quality. Theoretical/Academic Implications. The results confirm that board characteristics have an important influence on financial reporting quality, in line with the views that have been expressed by several international bodies. The findings also suggest that both researchers and policy makers should no longer consider institutional investors as a whole, given than directors appointed by different types of institutional investors have various implications on financial reporting quality, measured by the type of audit opinion. Practitioner/Policy Implications. This study makes its core contribution by empirically showing that directors appointed by different types of institutional investors have diverse implications on financial reporting quality. This evidence can be potentially helpful in providing a basis for regulatory actions, namely those aiming to influence the structure of the board of directors. The results have important implications for supervisors and regulators, who will benefit from an understanding of how the presence of directors on boards of savings and commercial banks in nonfinancial firms affects financial reporting quality in a bank‐based system.
Possibility for Selective Accumulation of Polyphenolics in Tissue Cultures of Senno (Lychnis Senno Siebold et Zucc.)

Senno (Lychnis senno Siebold et Zucc.), a traditional ornamental plant in Japan had been used as a crude drug acting as natural blood thinners. Since tissue culture protocols have been established, we analyzed polyphenol accumulation profiles in shoot culture, multiple shoot culture, and callus culture using the technique of HPLC with a Photodiode Array Detector. By comparing the HPLC profiles at 220-400 nm from extracts of different cultures, 14 putative flavonoids were confirmed as major metabolites in the cultures of Senno. Among the 14 compounds detected, 6 were tissue specific metabolites. It appears that the biosynthetic pathway of polyphenolics in Senno is regulated or strongly influenced by how tissues are regenerated and maintained in the in vitro environment. Hence, it may be possible to selectively produce novel secondary metabolites including flavonoids by engineering a target tissue culture procedure developed in the present study.
The Role of Application Assistance and Information in College Decisions: Results from the H&R Block FAFSA Experiment*

Growing concerns about low awareness and take-up rates for government support programs like college financial aid have spurred calls to simplify the application process and enhance visibility. We present results from a randomized field experiment in which low-income individuals receiving tax preparation help were also offered immediate assistance and a streamlined process to complete the Free Application for Federal Student Aid (FAFSA) for themselves or their children. Treated participants were also provided with aid estimates that were compared against tuition cost amounts for nearby colleges. The combined assistance and information treatment substantially increased FAFSA submissions and ultimately the likelihood of college attendance, persistence, and aid receipt. In particular, high school seniors whose parents received the treatment were 8 percentage points more likely to have completed two years of college, going from 28% to 36%, during the first three years following the experiment. Families who received aid information but no assistance with the FAFSA did not experience improved outcomes. The findings suggest many other opportunities for using personal assistance to increase participation in programs that require filling out forms to become eligible. JEL Codes: I2, H4, J24. Copyright 2012, Oxford University Press.
Major depression and posttraumatic stress disorder symptoms following severe burn injury in relation to lifetime psychiatric morbidity.

BACKGROUND Psychiatric history has been suggested to have an impact on long-term adjustment in burn survivors. A rigorous, prospective, longitudinal approach was used to study psychiatric history in a population-based burn sample and its impact on symptomatology of depression and posttraumatic stress disorder (PTSD) at a 12-month follow-up. METHODS Seventy-three consecutive patients admitted to the Uppsala Burn Unit were assessed with the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition for psychiatric disorders, of whom 64 were also assessed after 12 months. RESULTS Forty-eight patients (66%) presented with at least one lifetime psychiatric diagnosis; major depression (41%), alcohol abuse or dependence (32%), simple phobia (16%), and panic disorder (16%) were most prevalent. At 12-months postburn, 10 patients (16%) met criteria for major depression, 6 (9%) for PTSD, and 11 (17%) for subsyndromal PTSD. Patients with lifetime anxiety disorder and with lifetime psychiatric comorbidity were more likely to be depressed at 12 months, whereas those with lifetime affective disorder, substance use disorder and psychiatric comorbidity were more likely to have symptoms of PTSD. CONCLUSIONS Two-thirds of burn survivors exhibit a history of lifetime psychiatric disorders. Those with a psychiatric history have a higher risk of postburn psychiatric problems.
Psychological status of Sarajevo children after war: 1999-2000 survey.

AIM To make a survey of children's health and psychosocial needs after the 1992-1995 war in Sarajevo, Bosnia and Herzegovina. METHODS Representative samples of school-age children (n=310) from 6 public schools in the Sarajevo Canton, their parents (n=280), and teachers (n=156) were surveyed by means of self-administered questionnaires and standardized psychometric scale (Ryan-Wengers Schoolagers Coping Strategies Inventory). The survey was conducted in October-November 1999, approximately four years after the war. RESULTS At the time of survey, well-being of children in Sarajevo was still heavily impacted by many various unhealthy life conditions and psychosocial stressors. Many school-age children lived in unhealthy and dangerous environment, including overcrowded living conditions (40%), unsafe playgrounds (68%), and no access to sports fields (52%). Most felt unsafe on streets (74%), many (73%) coped with one or more school problems, and even 84% were ill at least once during the past 12 months. General poverty was the prime stressor (common variance explained: 23.5%), followed by school- and health-related risks (common variance explained: 17.0%). At the third place were family-associated risk factors impacting children's health and development, such as overcrowded living conditions and lack of social support within their own family (common variance explained: 10.5%). Parents and teachers also lived and worked in stressful life conditions and were concerned for both their children's and their own well-being. Despite all that, most children tended to use healthy strategies in coping with stressful events in their everyday lives. CONCLUSION The reinforcement of children with positive (healthy) coping skills and strengthening of their social support networks seems to be the most important intervention strategy to help the war-traumatized children in Bosnia and Herzegovina.
A systemic review of glutathione S-transferase P1 Ile105Val polymorphism and colorectal cancer risk.

OBJECTIVES To investigate the correlation between glutathione S-transferase P1 (GSTP1) Ile105Val polymorphism and colorectal cancer (CRC) risk. METHODS Studies were identified to investigate the association between GSTP1 Ile105Val polymorphism and CRC risk. Systematic computerized searches of the PubMed, Chinese National Knowledge Infrastructure, WANFANG and SinoMed were performed. Summary odds ratios (OR) and 95% confidence intervals (95% CI) were used to measure GSTP1 Ile105Val polymorphisms and CRC risk. RESULTS A total of 23 retrospective studies were included in the meta-analysis. During all studies including 6,981 cases and 8,977 controls, sample sizes ranged from 146 to 2,144. Overall, the pooled results revealed that Ile105Val polymorphism was not associated with CRC risk and confused results were found in subgroup analyses. Further meta-analyses were conducted after excluding low-quality studies. GSTP1 Ile105Val is associated with increased risk of CRC limited in studies with matched control. There was no significant heterogeneity in all genetic comparisons, but heterogeneity existed in subgroup analyses of heterozygous and dominant comparisons. The meta-regression analyses indicated that matched controls were the significant factor influencing between-study heterogeneity in all possible influential factors including published year, ethnicity, source of control, sample size, Hardy-Weinberg equilibrium (HWE) in control and matched controls. Sensitivity analysis revealed the pooled ORs were not changed before and after removal of each single study in all genetic comparisons, indicating the robustness of the results. CONCLUSIONS GSTP1 Ile105Val might be associated with increased risk of CRC. However, more high-quality case-control studies should be performed to confirm the authenticity of our conclusion.
Transmembrane helix connectivity in Orai1 controls two gates for calcium-dependent transcription

Characterization of disease-associated Orai1 mutants reveals the multistep gating mechanism for the CRAC channel. Characterizing cancer-associated Ca2+ channels Orai1 enables Ca2+ influx into cells in response to ER Ca2+ depletion, resulting in various Ca2+-dependent signaling events, including the stimulation of transcription factors such as NFAT. Frischauf et al. (see also the Focus by Muallem et al.) characterized various Orai1 mutants that they identified from cancer databases using cBioPortal and an Orai1 mutant associated with myopathy. The constitutively active mutants not only activated NFA but also stimulated mitophagy and autophagy, processes that can contribute to tumor progression. A combination of biochemical, electrophysiological, and structural analyses revealed how Orai1 is gated, how this Ca2+ channel can be in a partially active state, and how constitutively activating mutations result in increased Ca2+ influx. Because Orai1 is found in diverse cell types, these results have broad implications for Orai1-mediated Ca2+ signaling in homeostasis and disease. The channel Orai1 requires Ca2+ store depletion in the endoplasmic reticulum and an interaction with the Ca2+ sensor STIM1 to mediate Ca2+ signaling. Alterations in Orai1-mediated Ca2+ influx have been linked to several pathological conditions including immunodeficiency, tubular myopathy, and cancer. We screened large-scale cancer genomics data sets for dysfunctional Orai1 mutants. Five of the identified Orai1 mutations resulted in constitutively active gating and transcriptional activation. Our analysis showed that certain Orai1 mutations were clustered in the transmembrane 2 helix surrounding the pore, which is a trigger site for Orai1 channel gating. Analysis of the constitutively open Orai1 mutant channels revealed two fundamental gates that enabled Ca2+ influx: Arginine side chains were displaced so they no longer blocked the pore, and a chain of water molecules formed in the hydrophobic pore region. Together, these results enabled us to identify a cluster of Orai1 mutations that trigger Ca2+ permeation associated with gene transcription and provide a gating mechanism for Orai1.
Coping with Autonomy

Abstract The question examined in this article is how decentralization of power and responsibilities in public administration affects the interaction between bureaucrats and politicians. Three factors were identified as potential predictors: executive authority; the nature of administrative decision making; and the nature of the relationship between bureaucrats and union officials. Data were collected through a survey administered to ninety-eight senior bureaucrats at the county level in Norway. Correlation and hierarchical regression analyses revealed that the character of the relationship between bureaucrats and union officials had the greatest impact on the interaction between bureaucrats and politicians. The more trustful the relationship, the less the interaction, while the stronger the dependency of bureaucrats on unions, the more intensive the interaction. Decision making that involves negotiations increased interaction, as did the bureaucrats' perception of themselves as clearly superior to their staff – as opposed to a perception of themselves as being in an advisory position.
Contributions to the morphology of the human coronary sinus.

The configuration and morphological features of the coronary sinus (c.s.) were studied on 54 human adult hearts. The c.s. has on an average 36 mm in length and 9 mm in diameter. The most frequent is the cylindrical configuration (67%), then follows the so-called "wafer" form (19%) and the funnel shaped c.s. (13%). The valve of Vieussens was present in 78%, but well developed only in 6% of the cases. The classical opening of the middle and small cardiac veins into c.s. was remarked in 28%; for the rest the particular forms described in this work make themselves obvious. The large tributaries of c.s. are provided with ostial valves in a percentage of 41%. The form and dimensions of the Thebesius valve are very variable; it is absent in 9% of the cases. The Marshall's vein appears as an obturated cord in a proportion of 20%. In each case there was found on the surface of the c.s. a myocardial coat, consisting of two layers, which form a device having probably a constrictive function during the atrial systole.
Demand Modelling Methodologies: Integration and other Issues

The exponential growth in tourist numbers motivates serious analysis of this phenomenon. The econometric methods commonly used do not take this central feature of demand seriously in the form and estimating of tourism demand models. Cointegration analysis has been used in recognition of the problem as a technical estimation issue. But this is unsatisfactory, due to both technical methodological concerns with the use of cointegration analysis and because it overcomes the growth issue rather than incorporating it into the model. A model form which does incorporate growth is proposed. Other, newer methods – neural networks and structural equations modelling – are sometimes applied, but these too are not unproblematic.
Idiopathic hypereosinophilic syndrome associated with cutaneous infarction and deep venous thrombosis

Summary We report a case of idiopathic hypereosinophilic syndrome (HES) presenting with cutaneous infarction and subsequent extensive deep vein thrombosis. The eosinophilia improved dramatically with systemic corticosteroid therapy. A variety of skin disorders have been associated with HES, although there are no previous reports of HES associated with cutaneous infarction. HES is a rare disorder characterized by a sustained overproduction of eosinophils and multisystem disease. The aetiology of the eosinophilia remains uncertain but clonal populations of abnormal T‐cells producing interleukin 5 may be implicated.
DNA damage induced by topoisomerase inhibitors activates SAMHD1 and blocks HIV‐1 infection of macrophages

We report that DNA damage induced by topoisomerase inhibitors, including etoposide (ETO), results in a potent block to HIV‐1 infection in human monocyte‐derived macrophages (MDM). SAMHD1 suppresses viral reverse transcription (RT) through depletion of cellular dNTPs but is naturally switched off by phosphorylation in a subpopulation of MDM found in a G1‐like state. We report that SAMHD1 was activated by dephosphorylation following ETO treatment, along with loss of expression of MCM2 and CDK1, and reduction in dNTP levels. Suppression of infection occurred after completion of viral DNA synthesis, at the step of 2LTR circle and provirus formation. The ETO‐induced block was completely rescued by depletion of SAMHD1 in MDM. Concordantly, infection by HIV‐2 and SIVsm encoding the SAMHD1 antagonist Vpx was insensitive to ETO treatment. The mechanism of DNA damage‐induced blockade of HIV‐1 infection involved activation of p53, p21, decrease in CDK1 expression, and SAMHD1 dephosphorylation. Therefore, topoisomerase inhibitors regulate SAMHD1 and HIV permissivity at a post‐RT step, revealing a mechanism by which the HIV‐1 reservoir may be limited by chemotherapeutic drugs.
Determinants of bank profitability in a developing economy: Empirical evidence from Bangladesh

This study seeks to examine the performance of 37 Bangladeshi commercial banks between 1997 and 2004. The empirical findings of this study suggest that bank specific characteristics, in particular loans intensity, credit risk, and cost have positive and significant impacts on bank performance, while non‐interest income exhibits negative relationship with bank profitability. During the period under study the results suggest that the impact of size is not uniform across the various measures employed. The empirical findings suggest that size has a negative impact on return on average equity (ROAE), while the opposite is true for return on average assets (ROAA) and net interest margins (NIM). As for the impact of macroeconomic indicators, we conclude that the variables have no significant impact on bank profitability, except for inflation which has a negative relationship with Bangladeshi banks profitability.
Effects of Unemployment on the Family

This paper reviews evidence about the incidence and impact of unemployment on the family. It finds that while the unemployment rate faced by husbands and wives is relatively low, many unemployed people fall into this category (36.2% were husbands and wives in 1998). Sole parents have a high unemployment rate. Hence, around one-third of unemployment is borne by parents with dependent children. Joblessness in families is also examined. The impacts of unemployment on families include poverty and hardship, strained relationships, poorer health (although the causal relationships are not always clear), and housing stress. Unemployment could also harm children's development and employment futures. Some policy issues are explored including the need to provide protection for the living standards for families affected by unemployment and taking a number of actions to reduce unemployment. The dilemmas posed by mutual obligation and the trend to precarious low-paid work are also raised.
Are emerging economies less efficient? Performance persistence and the impact of business group affiliation

By drawing a theoretical distinction between the persistence of superior and poor performance, we reconcile the conflicting predictions of the ‘revisionist’ and accepted views on the persistence of firm performance in emerging economies. Using a sample of manufacturing firms in the United States and India, we show that superior firm performance in emerging economies persists only as much as developed economies in line with the revisionist argument. We also provide evidence consistent with the accepted view that poor firm performance persists longer in emerging economies compared to developed economies. Further exploration of the latter shows that, contrary to predictions of extant theories, firms in emerging economies that are affiliated with an MNC or a business group have a greater persistence of poor performance than firms that are unaffiliated with these intermediate governance structures, and hence would be better off operating at arm's length. Copyright © 2005 John Wiley & Sons, Ltd.
Carbon emission reduction and cost–benefit of methane digester systems on hog farms in China

Three different sizes of hog farms were selected to analyze the carbon emissions reduction and the cost–benefit of three methane digester systems. The sizes of the digesters are 2,200, 2,200 and 800 m3, respectively. The sales of slaughter hogs from them are 50,000, 35,000 and 10,000 head, respectively. The carbon emissions reductions were 5,237, 4,017, and 1,334 tons, respectively. The results show that while the methane digester systems have a significant effect on carbon emissions reduction, it is difficult to operate the systems sustainably. If the carbon emissions reduction can be traded at high enough prices in the carbon offset markets, then the systems will be profitable and sustainable. Newly established China's domestic carbon offset market could provide this possibility, but more government support is needed. In addition, this study shows that scale economies make the digester adoption relatively more profitable for larger farms than smaller ones.