Miracle-dz/UniFAR-FTUs huggingface dataset:
Differences in Effects on Myocardium and Mitochondria by Angiogenic Inhibitors Suggest Separate Mechanisms of Cardiotoxicity

Several multikinase angiogenesis inhibitors demonstrate mitochondrial and/or cardiovascular toxicity, suggesting an on-target pharmacologic effect. To evaluate whether cardiotoxicity is directly related to vascular endothelial growth factor receptor inhibition, we investigated the effects of sunitinib, sorafenib, and pazopanib on myocardial function and structure. We used a rat model to assess myocardial effects of the inhibitors concurrently exposed to the cardiac stressor dobutamine. Echocardiographic abnormalities including premature ventricular contractions, decreases in heart rate, circumferential strain, and radial and circumferential strain rates were noted with sorafenib, but not with sunitinib or pazopanib. Ultrastructural analysis of ventricular cardiomyocytes by transmission electron microscopy revealed mitochondrial swelling, dense deposits, and matrix cavitation in rats given sunitinib and disrupted mitochondrial cristae in rats given sorafenib, but there were no effects with pazopanib. Effects on neonatal rat cardiomyocyte cultures were assessed, which identified decreases in mitochondrial membrane potential with sunitinib treatment, but not with sorafenib or pazopanib. Intracellular adenosine triphosphate depletion was observed with sunitinib and sorafenib, but not pazopanib. Our results show that cardiotoxicity is not necessarily related to a pharmacologic classwide effect of vascular endothelial growth factor receptor inhibition, and the rat myocardial structural and functional changes identified in this study may be instead a result of inhibition of other kinase pathways, the mechanism of which may be associated with mitochondrial toxicity.
Performance Effects of Global Account Coordination Mechanisms: An Integrative Study of Boundary Conditions

Although many multinational companies have instituted global account management (GAM) programs to coordinate selling activities to better serve and retain their key global customers, evidence of the effectiveness of their GAM coordination efforts is elusive. Viewing GAM coordination as an organizational design issue in managing vertical procurement relationships, the authors draw on global marketing strategy, organizational design, and relationship marketing theories to study how the performances of GAM coordination mechanisms vary with a host of strategic, relational, and environmental conditions. The conceptual model is tested using data collected from a cross-national sample of more than 200 global account managers. The results show that although GAM relational coordination and GAM operational coordination both have positive effects on GAM performance, they do not perform uniformly well under various boundary conditions. In other words, the performance of a GAM coordination mechanism depends on its fit with the operating context.
Use of bisphosphonates and reduced risk of colorectal cancer.

PURPOSE Bisphosphonates are commonly used for the treatment of osteoporosis and bone metastases caused by breast cancer and were recently reported to be associated with a reduced risk of breast cancer, possibly acting through the mevalonate pathway, but their association with risk of other cancers is unknown. PATIENTS AND METHODS The Molecular Epidemiology of Colorectal Cancer study is a population-based, case-control study in northern Israel of patients with colorectal cancer and age-, sex-, clinic-, and ethnic group-matched controls. Long-term use of bisphosphonates before diagnosis was assessed in a subset of 933 pairs of postmenopausal female patients and controls, enrolled in Clalit Health Services, using computerized pharmacy records. RESULTS The use of bisphosphonates for more than 1 year before diagnosis, but not for less than 1 year, was associated with a significantly reduced relative risk (RR) of colorectal cancer (RR, 0.50; 95% CI, 0.35 to 0.71). This association remained statistically significant after adjustment in a model for vegetable consumption, sports activity, family history of colorectal cancer, body mass index, and use of low-dose aspirin, statins, vitamin D, and postmenopausal hormones (RR, 0.41; 95% CI, 0.25 to 0.67). Concomitant use of bisphosphonates and statins did not further reduce the risk. CONCLUSION The use of oral bisphosphonates for more than 1 year was associated with a 59% relative reduction in the risk of colorectal cancer, similar to the recently reported association of this drug class with reduction in breast cancer risk.
Retinal pigment epithelial integrity is compromised in the developing albino mouse retina

In the developing murine eye, melanin synthesis in the retinal pigment epithelium (RPE) coincides with neurogenesis of retinal ganglion cells (RGCs). Disruption of pigmentation in the albino RPE is associated with delayed neurogenesis in the ventrotemporal retina, the source of ipsilateral RGCs, and a reduced ipsilateral RGC projection. To begin to unravel how melanogenesis and the RPE regulate RGC neurogenesis and cell subpopulation specification, we compared the features of albino and pigmented mouse RPE cells during the period of RGC neurogenesis (embryonic day, E, 12.5 to 18.5) when the RPE is closely apposed to developing RGC precursors. At E12.5 and E15.5, although albino and pigmented RPE cells express RPE markers Otx2 and Mitf similarly, albino RPE cells are irregularly shaped and have fewer melanosomes compared with pigmented RPE cells. The adherens junction protein P‐cadherin appears loosely distributed within the albino RPE cells rather than tightly localized on the cell membrane, as in pigmented RPE. Connexin 43 (gap junction protein) is expressed in pigmented and albino RPE cells at E13.5 but at E15.5 albino RPE cells have fewer small connexin 43 puncta, and a larger fraction of phosphorylated connexin 43 at serine 368. These results suggest that the lack of pigment in the RPE results in impaired RPE cell integrity and communication via gap junctions between RPE and neural retina during RGC neurogenesis. Our findings should pave the way for further investigation of the role of RPE in regulating RGC development toward achieving proper RGC axon decussation. J. Comp. Neurol. 524:3696–3716, 2016. © 2016 Wiley Periodicals, Inc.
Life Cycle Assessment and the U.S. Policy-Making Context

Environmental policy makers use life cycle assessment (LCA) to reduce scientific uncertainties about the environmental impact of technologies and products. However, the structure of the U.S. policymaking system often acts as a roadblock to the use of LCA outputs in decision making. Over the past two decades/life cycle assessment has had limited impact in determining U.S. environmental policy, either as a specific quantitative indicator or as a general outlook toward the environment. In this chapter, I discuss specific characteristics of the U.S. political system, which often make uncertainty-reducing assessments like life cycle assessment fail in a decision-making context: the incremental nature of the U.S. policy-making system; the
Public Service Motivation: A Systematic Literature Review and Outlook

Over the past two decades, research on public service motivation has seen rapid growth. Despite the relatively large number of publications to date, no systematic research overview has been created, leaving the body of literature somewhat unstructured and possibly hampering future research. This article fills this void by providing a systematic literature review of 323 publications that examines six key aspects of the literature on public service motivation: the growth of research on the concept, the most prominent studies based on a referencing network analysis, the most frequent publication outlets, research designs and methods, lines of inquiry and patterns of empirical findings, and implications for practice drawn from the publications in the study sample. Strengths and weaknesses of the existing literature are identified, and future research directions are proposed.
Crash Risk and the Auditor-Client Relationship

This study examines whether the term of the auditor-client relationship (i.e., auditor tenure) is associated with future stock price crash risk measured both ex ante and ex post. Using a large sample of U.S. public firms with Big Four auditors, we find robust evidence that auditor tenure is negatively related to one-year-ahead stock price crash risk. The evidence is consistent with monitoring-by-learning where development of client-specific knowledge over the term of the auditor-client relationship enhances auditors’ ability to detect and deter bad news hoarding activities by clients, thereby reducing future crash risk. This result holds even after controlling for endogeneity of the tenure/crash risk relation. We further provide evidence indicating that option market investors do not fully incorporate the information contained in the term of auditor-client relationship in predicting future stock price crash risk. Our empirical results have important policy implications for regulators concerned with ensuring auditor independence.
Change in University-Based Programs of Educational Leadership

Much of the literature criticizing university-based school leadership preparation programs concludes that programs are, at best, reluctant to change, a conclusion often based more on anecdotal stories than a more systematic inquiry. This article provides evidence on the extent of change in programs since passage of the Standards for Advanced Programs in Educational Leadership in 2002. Chairs at National Council for Accreditation of Teacher Education–accredited schools were surveyed to determine the nature and extent of adoption of design elements associated with effective programs. Descriptive and inferential statistics were used to demonstrate that there has been wide-ranging change in university programs, and that the extent of this change does not depend on type of university or membership in University Council for Educational Administration.
Efficiency of automata in semi-commutation verification techniques

Computing the image of a regular language by the transitive closure of a relation is a central question in Regular Model Checking. In a recent paper Bouajjani, Muscholl and Touili \cite{Anca} proved that the class of regular languages L -- called APC -- of the form of a union of L{0,j}L{1,j}L{2,j}. L{k_j,j}$, where the union is finite and each L{i,j} is either a single symbol or a language of the form B* with B a subset of the alphabet, is closed under all semi-commutation relations R. Moreover a recursive algorithm on the regular expressions was given to compute R*(L). This paper provides a new approach, based on automata, for the same problem. Our approach produces a simpler and more efficient algorithm which furthermore works for a larger class of regular languages closed under union, intersection, semi-commutation relations and conjugacy. The existence of this new class, PolC, answers the open question proposed in the paper of Bouajjani and al.
Enhanced tunable characteristics of the Na/sub 0.5/Bi/sub 0.5/TiO/sub 3/-NaTaO/sub 3/relaxor-type system

We have investigated the voltage-tunable characteristics of the Na<sub>0.5</sub>Bi<sub>0.5</sub>TiO<sub>3</sub>-NaTaO<sub>3</sub> homogeneity region, for which samples were prepared using a conventional solid-state reaction. The highest value of the relative tunability (n<sub>r</sub>) was obtained for the sample with 5 mol% of NaTaO<sub>3</sub>, i.e., 47% at 1 MHz and a 70 kV/cm dc bias field. This sample also showed the highest value of the dielectric losses (tan delta) and temperature coefficient of the dielectric constant (tau<sub>epsiv</sub>), i.e., 0.05 and 4478 ppm/K, respectively. As the concentration of NaTaO<sub>3</sub> increased up to 90 mol% n<sub>r</sub>, tan delta, and tau<sub>epsiv</sub> gradually decreased toward 22%, 0.0002 and -899 ppm/K, respectively. The dielectric constant of the samples varied in a similar manner between 662 and 130. At microwave frequencies, the dielectric losses of the samples substantially increased due to their relaxor-type nature. The lowest value was obtained for the samples with 90 mol% of NaTaO<sub>3</sub>, i.e., 0.002. The tunable characteristics of the samples are related to the ferroelectric and dielectric properties, and it appears that the dielectric tunability of the Na<sub>0.5</sub>Bi<sub>0.5</sub>TiO<sub>3</sub>-NaTaO<sub>3</sub> system originates from its relaxor-type behavior.
Polymorphisms in the sodium-dependent ascorbate transporter gene SLC23A1 are associated with susceptibility to Crohn disease.

BACKGROUND Crohn disease (CD) and ulcerative colitis (UC) are 2 common inflammatory bowel diseases (IBDs) associated with intestinal inflammation and tissue damage. Oxidative stress is suggested to play a major role in the initiation and progression of IBD. Vitamin C (ascorbate, ascorbic acid) supplementation has reduced oxidative stress in persons with IBD. The role of ascorbate transporters in IBD remains to be determined. SLC23A1 is a major ascorbate transporter in the intestinal tract, and some of its genetic variants have been associated with severely decreased ascorbate transport and lower systemic concentrations. OBJECTIVE This study aimed to determine whether common genetic variants in the vitamin C transporter SLC23A1 are associated with the risk of IBD. DESIGN Genomic DNA samples from patients with CD (n = 162) and UC (n = 149) from the Manitoba IBD Cohort Study and ethnically matched controls (n = 142) were genotyped for 3 SLC23A1 polymorphisms (rs6596473, rs33972313, and rs10063949) by using TaqMan assays. RESULTS Variation at rs10063949 (G allele for heterozygote and homozygote) was associated with increased susceptibility to CD (OR: 2.54; 95% CI: 1.38, 4.66; OR: 4.72; 95% CI: 2.53, 8.81; P < 0.0001; respectively). A strong linkage disequilibrium (LD) was observed across the SLC23A1 region (variation rs6596473 with rs10063949) for CD and UC (D' = 0.94 and 0.96, respectively). The risk alleles confirmed a haplotype (CGG) that is carried more in CD patients (65.3%, P < 0.0001) than in controls (43.5%). CONCLUSIONS A genetic variant (rs10063949-G) in the SLC23A1 ascorbate transporter locus was identified and is associated with an increased risk of CD in a white Canadian IBD cohort. The presented evidence that SLC23A1 variations can modulate the risk of CD has implications for understanding ascorbate transport in CD patients and provides a novel opportunity toward individualized nutritional therapy for patients carrying the disease-associated genotype.
Modelling Long Maturity Forward Rates with Overshooting

It is natural to assume that interest rates mean-revert, and natural consequence of this is that long forward rates are asymptotically constant. However, from US Treasury STRIPs data, forward rates slope increasingly downwards, and do not attenuate in volatility, as maturity increases beyond about 15 years.We fit an equilibrium model which reconciles this behavior with mean reversion. The key is to extract a latent factor, which the forward rate follows, but overshoots, causing mean reversion on a time scale in terms of weeks. This allows the forward rates to mean revert over the long term in the objective measure but not in the risk neutral measure. We show that this mean reversion can in principle be exploited for profit.Our model falls into the Essentially Affine class. We finally set our analysis in the context of similar models for shorter maturities, and discuss applications to managing positions in long maturity bonds and associated derivatives.
Incorporating data into grazing management decisions: supporting farmer learning

Pasture consumption is an important contributor to farm business profitability in pasture based dairy systems around the world, including Tasmania. Research, development and extension prioritizes further increasing pasture consumption in the Tasmanian dairy industry, through progressing technical innovations and providing services to support increased farmer adoption of proven practices. Increasing farmer adoption of best practice grazing management recommendations relies on the continued development of extension delivery to meet farmer information and skill development needs. A social research study identified some of these needs by exploring pasture management approaches and associated learning processes of farmers whose practices were more versus less aligned to recommended practices. The aim was to improve understanding of the grazing management learning process and implications for extension in the context of data made available through new technology. Qualitative interview data revealed that pasture managers whose practices are more closely aligned to recommended practices have used pasture measurement tools and carried out associated calculations intensively for an extended period (≥ 1 year), before adapting best practices to suit their farm management approach. Less aligned pasture managers were aware of the importance of grazing management, but were less aware they lacked knowledge and skills required to implement recommended practices. The data suggest there is ‘unconscious incompetence’ at play, and that these farmers had not engaged in a supported learning process. These findings suggest that introducing innovative ways to acquire pasture growth data will not result in practice change unless dairy farmers have progressed through the grazing management learning process and come to understand how to use data effectively.
Life after Sheffield

Follow-up surveys of Masters programme graduates at the Department of Information Studies have been conducted at regular intervals since 1973. The findings of these reviews are outlined here, with particular reference to graduates’ perceptions of the relevance and value of the programmes they followed to their subsequent professional employment, and to factors affecting their job satisfaction in first and subsequent posts. Overall, graduates surveyed commented favourably on the quality and relevance of the programmes while making positive suggestions as to how the programmes might be improved. Factors affecting job satisfaction varied, depending on job destinations and employment sector, as did the commonest causes of job dissatisfaction.
A comparative analysis of postpartum maternal mental health in women following spontaneous or ART conception

Abstract Objective: To determine whether conception following assisted reproductive technology (ART) predisposes women to increased risk of postnatal depression (PND), compared to women who conceived naturally, when controlling for such factors as: multiple birth, previous maternal psychiatric history and sociodemographic status. Participants: A total of 200 women who attended the private antenatal and fertility clinics of a fertility specialist in a large Australian city between January 2009 and December 2011 were contacted via telephone. Results: There was no difference in the rate of PND between the two groups (7.5% versus 7.4%, p = ns). Aside from the slightly older maternal age in the ART group (35.4 versus 33, p < 0.05), baseline socio-demographics were similar. There was a significantly higher rate of previous maternal clinical depression in the ART group compared to the controls (17% versus 5%, p < 0.05); however, other known risk factors for PND, including previous PND (10.6% versus 13.7%, p = ns), multiple births (2.1% versus 4.2%, p = ns) and low infant birth weight (3.3 kg versus 3.4 kg, p = ns), were not different in the two cohorts. Women who conceived naturally were also more likely to breastfeed for a longer duration (78% versus 89%, p < 0.05). Conclusion: Our study demonstrates that when accounting for well-known risk and protective factors for postpartum depression, women who conceive using ART are not at an increased risk PND. In addition, the low rate of multiple births in the ART group further validates the practice of single embryo transfer.
Travel During Pregnancy: Considerations for the Obstetric Provider.

Importance Travel among US citizens is becoming increasingly common, and travel during pregnancy is also speculated to be increasingly common. During pregnancy, the obstetric provider may be the first or only clinician approached with questions regarding travel. Objective In this review, we discuss the reasons women travel during pregnancy, medical considerations for long-haul air travel, destination-specific medical complications, and precautions for pregnant women to take both before travel and while abroad. To improve the quality of pretravel counseling for patients before or during pregnancy, we have created 2 tools: a guide for assessing the pregnant patient's risk during travel and a pretravel checklist for the obstetric provider. Evidence Acquisition A PubMed search for English-language publications about travel during pregnancy was performed using the search terms "travel" and "pregnancy" and was limited to those published since the year 2000. Studies on subtopics were not limited by year of publication. Results Eight review articles were identified. Three additional studies that analyzed data from travel clinics were found, and 2 studies reported on the frequency of international travel during pregnancy. Additional publications addressed air travel during pregnancy (10 reviews, 16 studies), high-altitude travel during pregnancy (5 reviews, 5 studies), and destination-specific illnesses in pregnant travelers. Conclusions and Relevance Travel during pregnancy including international travel is common. Pregnant travelers have unique travel-related and destination-specific risks. We review those risks and provide tools for obstetric providers to use in counseling pregnant travelers.
Influence of weed management practices on weed dynamics and yield of urdbean (Vigna mungo) under rainfed conditions of Jammu

Experiments were conducted during kharif 2007 and 2009 in Inceptisols, to study the effect of different pre (PE) and post-emergence (POE) herbicides along with two hand weedings (HW) at 20 and 40 days after sowing (DAS) and weedy check on urdbean {Vigna mungo (L.) Hepper}. Highest seed yield was observed with two HWs at 20 and 40 DAS and the values were found statistically at par with POE application of imazethapyr 25 g/ha at 20 DAS. The highest weed control efficiency and lowest weed biomass was recorded with two HWs at 20 and 40 DAS fol- lowed by application of imazethapyr 25 g/ha (post-emergence) at 20 DAS. Application of Fenoxaprop-p-ethyl, quizalofop-p-ethyl, chlorimuron-p-ethyl as post-emergence and their combinations also reduced weed biomass and improved seed yield and yield attributing parameters as compared to weedy check. Treatment weedy check registered the highest values of weed count and weeds biomass and lowest seed yield and yield attributing char- acters in both the years of study. Rainfall was directly related to weed count and weed dry matter accumulation with the coefficient of 0.65 and 0.61, respectively. Weed dry matter accumulation was directly related with sun- shine hours with an accuracy of 67%, whereas, weed count was lesser related with sunshine hours of the day with an accuracy of 34%. Grain and biological yield of urdbean crop decreased at the rate of 3.3 and 7.5 kg/ha under weedy check with an accuracy of 88 and 73%, respectively.