Miracle-dz/UniFAR-FTUs huggingface dataset:
Concordance between Results of Medium-term Liver Carcinogenesis Bioassays and Long-term Findings for Carcinogenic 2-Nitropropane and Non-carcinogenic 1-Nitropropane in F344 Rats

This study was conducted to determine the concordance of results for a pair of structural isomers, 2-nitropropane (2-NP) and 1-nitropropane (1-NP), using the rat medium-term liver carcinogenesis bioassay (Ito test) and previously published long-term carcinogenicity tests. Male F344 rats were given a single intraperitoneal injection of DEN (200 mg/kg b.w.) to initiate hepatocarcinogenesis. After 2 weeks, they received per os 0, 0.8, 4 or 20 mg/kg/day of 2-NP or 1-NP six times a week and were subjected to two-thirds partial hepatectomy at week 3. Non-initiated groups receiving 0 or 20 mg/kg/day were also included. The animals were sacrificed for quantitative analysis of GST-P-positive foci at week 8. With the highest dose of 2-NP, significantly increased numbers and areas of GST-P-positive foci were demonstrated as compared with the respective control but were not noted with 1-NP. In the non-DEN-initiated groups, many small GST-P-positive foci of less than 0.2 mm in diameter were also induced in the rats treated with 2-NP at 20 mg/kg/day but were lacking with 1-NP. These results strongly support that 2-NP is a complete hepatocarcinogen with a potent initiation activity, whereas 1-NP is not.
Examining students’ self-set goals for self-regulated learning: Goal properties and patterns

Task-specific goals play a critical role in self-regulated learning, yet little research has examined students’ self-set goals for authentic study sessions. We propose high-quality goals that are useful for guiding task engagement and evaluating progress are specific about (a) time, (b) actions, (c) standards, and (d) content. In Study 1, we examined characteristics of students’ self-set goals. Five categories were created to describe students’ goals relative to the features of a high-quality goal. Students rarely included specific information regarding actions, standards, or content. In Study 2, we examined patterns of change in quality of self-set goals across a semester in which students were in a learning-to-learn course. Improvements in goal quality were either inconsistent or non-existent. Implications of vague goals for regulating learning are discussed.
Pharmacological targeting the ATR–CHK1–WEE1 axis involves balancing cell growth stimulation and apoptosis

The ATR–CHK1–WEE1 kinase cascade's functions in the DNA damage checkpoints are well established. Moreover, its roles in the unperturbed cell cycle are also increasingly being recognized. In this connection, a number of small-molecule inhibitors of ATR, CHK1, and WEE1 are being evaluated in clinical trials. Understanding precisely how cells respond to different concentrations of inhibitors is therefore of paramount importance and has broad clinical implications. Here we present evidence that in the absence of DNA damage, pharmacological inactivation of ATR was less effective in inducing mitotic catastrophe than inhibition of WEE1 and CHK1. Small-molecule inhibitors of CHK1 (AZD7762) or WEE1 (MK-1775) induced mitotic catastrophe, as characterized by dephosphorylation of CDK1Tyr15, phosphorylation of histone H3Ser10, and apoptosis. Unexpectedly, partial inhibition of WEE1 and CHK1 had the opposite effect of accelerating the cell cycle without inducing apoptosis, thereby increasing the overall cell proliferation. This was also corroborated by the finding that cell proliferation was enhanced by kinase-inactive versions of WEE1. We demonstrated that these potential limitations of the inhibitors could be overcome by targeting more than one components of the ATR–CHK1–WEE1 simultaneously. These observations reveal insights into the complex responses to pharmacological inactivation of the ATR–CHK1–WEE1 axis.
De novo post-transplant thrombotic microangiopathy localized only to the graft in autosomal dominant polycystic kidney disease with thrombophilia

Introduction: Thrombotic microangiopathy (TMA) is a serious complication of renal transplantation and is mostly related to the prothrombotic effect of calcineurin inhibitors (CNIs). A subset of TMA (29%-38%) is localized only to the graft. Case 1: A young woman suffering from autosomal dominant polycystic kidney disease (ADPKD) underwent kidney transplant. After 2 months, she showed slow renal deterioration (serum creatinine from 1.9 to 3.1 mg/dl), without hematological signs of hemolytic-uremic syndrome (HUS); only LDH enzyme transient increase was detected. Renal biopsy showed TMA: temporary withdraw of tacrolimus and plasmapheresis was performed. The renal function recovered (serum creatinine 1.9 mg/dl). From screening for thrombophilia, we found a mutation of the Leiden factor V gene. Case 2: A man affected by ADPKD underwent kidney transplantation, with delay graft function; first biopsy showed acute tubular necrosis, but a second biopsy revealed TMA, while no altered hematological parameters of HUS was detected. We observed only a slight increase of lactate dehydrogenase (LDH) levels. The tacrolimus was halved and plasmapheresis was performed: LDH levels normalized within 10 days and renal function improved (serum creatinine from 9 to 2.9 mg/dl). We found a mutation of the prothrombin gene. Only a renal biopsy clarifies the diagnosis of TMA, but it is necessary to pay attention to light increasing level of LDH. Conclusion: Prothrombotic effect of CNIs and mTOR inhibitor, mutation of genes encoding factor H or I, anticardiolipin antibodies, vascular rejection, cytomegalovirus infection are proposed to trigger TMA; we detected mutations of factor II and Leiden factor V, as facilitating conditions for TMA in patients affected by ADPKD.
Novel advances in the treatment of osteoporosis.

INTRODUCTION Osteoporosis is a significant public health issue affecting over half of women aged over 50. With an aging population, its importance is set to increase further over time. Prevention of fragility fractures avoids significant mortality and morbidity as well as saving significant direct and indirect costs to the economy. In this review, we discuss existing treatments to contextualize the treatment landscape, and demonstrate how our understanding of bone pathophysiology has led to novel therapies-in the form of combinations and altered durations of existing treatments, as well as newer drug therapies. SOURCES OF DATA PubMed and Embase were searched for randomized controlled trials of new therapies for osteoporosis. These searches were supplemented with material presented in abstract form at international meetings. AREAS OF AGREEMENT New drugs that appear promising in the treatment of osteoporosis include the cathepsin K inhibitor, monoclonal antibodies against sclerostin and parathyroid hormone-related protein analog. AREAS OF CONTROVERSY Separate to the development of novel drug therapies is the issue of how best to use agents that are currently available to us; specifically which agent to choose, alone or in combination; duration of therapy; how best to identify patients at highest risk of fracture, and to ensure the highest possible adherence to medication. Many of these issues have been addressed in other excellent review papers, and will not be considered in detail here. GROWING POINTS As with all new treatments, we await results of long-term use and experience in 'real life' patient populations. AREAS TIMELY FOR DEVELOPING RESEARCH As alluded to above, data are urgently required regarding the optimal duration of therapy; use of combination therapy; ordering of therapies for best therapeutic effect. As stratified medicine becomes more strongly considered in all areas of therapy, its merits in osteoporosis as in other musculoskeletal conditions, is timely and valuable.
The Linearity of the End‐systolic Pressure‐Volume Relationship in Man and Its Sensitivity for Assessment of Left Ventricular Function

The linearity and sensitivity of the end-systolic pressure-volume (P-Ves) relation to the inotropic state of the left ventricle were investigated in 11 patients with coronary heart disease and one patient with congestive cardiomyopathy. To minimize autonomic reflex responses, propranolol, 0.15 mg/kg, and atropine, 1 mg, were administered i.v. at the beginning of the study. Three ventriculograms were performed: at rest, after oral isosorbide dinitrate, 10 mg (systolic pressure decrease 15 ⩾ mm Hg), and during infusion of methoxamine, 2 mg/min (systolic pressure increase ⩾ 10 mm Hg). The three points of the P-Ves relation showed linearity (r ⩾ 0.96). The relation between the slope k of the PVes relation and the left ventricular ejection fraction at rest was best described by an exponential function (r = 0.94). The use of peak systolic pressure instead of end-systolic pressure showed equally good results. The intercept of the PVes line on the abscissa, which represents the theoretical end-systolic volume at zero pressure, was not related to the ejection fraction under control conditions. The P-Ves relation in postextrasystolic beats was displaced toward the left (smaller end-systolic volumes) and became steeper.
Investigation of adaptive split-belt treadmill walking by the hindlimbs of rats

In this study, we investigated the adaptive behavior during hindlimb locomotion of rats on a split-belt treadmill. We measured and analyzed the movement of intact rats walking by the hindlimbs on the splitbelt treadmill with two conditions: symmetric and asymmetric belt speed. In addition, we conducted the dynamic simulation of a neuromusculoskeletal model of rat's hindlimb walking on a split-belt treadmill. We investigated the immediate modulations of the duty factors and relative phase between the right and left limbs depending on the conditions of the treadmill. The results of the simulation were qualitatively similar to those of the measurement experiment. Furthermore, these results were qualitatively similar to the measurement data of the humans and cats in the previous studies. This suggests that our model have the essential aspects to produce the adaptive split-belt treadmill walking in dynamics viewpoints.
Not the usual suspects: How to use board process to make boards better

Executive Overview Research on corporate boards and board reform efforts alike have been dominated by a concern for board independence and its effect on the monitoring of the CEO. However, attention to what we call the “usual suspects”—the number of outsiders on boards, director shareholdings, board size, and whether the CEO also holds the Chair position (CEO duality)—does not yield either strong research results or more robust corporate governance in practice. In this article we argue that the “usual suspects,” as measured by the classic indicators, do not ensure a truly independent board and that the key to making boards work better rests in an area largely ignored by researchers: board process. Based on structured interviews with members of corporate boards, we open a window to what is really going on inside boardrooms. Our analysis suggests five critical goals for which all boards should strive and presents a detailed checklist of recommendations for directors on how best to realize these goals.
The Role of Cognitive Emotion Regulation Strategies, Emotional Expressivity, and Ambivalence Over Emotional Expression on Cognitive Stress Appraisals and Cardiovascular Reactivity During an Acute Interpersonal Stress Recall Task

2014 ii Acknowledgments I have an immense amount of gratitude and special thanks to my primary thesis advisor, Dr. David Chatkoff. His incredible expertise in regards to the stress and cardiovascular literature, time and devotion given in assisting to collect such a rigorous research thesis, his warm and open demeanor, as well as his desire to help me succeed with my research and professional career has been amazing. I would also like to give a special thank you to my second advisor, Dr. Michelle Leonard for her collaboration, wonderful input, wealth of knowledge, and support in my research endeavors. I want to also, acknowledge the U of M-Dearborn psychology team that assisted with data collection and entry. Lastly, I would like to thank my wonderful family and friends for their caring support, snacks in the middle of the night, and strong motivation at all hours of the day and night to stay dedicated to my school and research work that will assist me in furthering my psychology career.
Modelling galaxy spectra in presence of interstellar dust – I. The model of interstellar medium and the library of dusty single stellar populations

The advent of modern infrared astronomy has brought into evidence the role played by the interstellar dust in galaxy formation and evolution. Therefore, to fully exploit modern data, realistic spectrophotometric models of galaxies must include this important component of the interstellar medium (ISM). In this paper, the first of a series of two devoted to modelling the spectra of galaxies of different morphological type in presence of dust, we present our description of the dust both in the diffuse ISM and the molecular clouds (MCs). Our galaxy model contains three interacting components: the diffuse ISM, made of gas and dust, the large complexes of MCs in which active star formation occurs and, finally, the populations of stars that are no longer embedded in the dusty environment of their parental MCs. Our model for the dust takes into account three components, i.e. graphite, silicates and polycyclic aromatic hydrocarbons (PAHs). We consider and adapt to our aims two prescriptions for the size distribution of the dust grains and two models for the emission of the dusty ISM. We cross-check the emission and extinction models of the ISM by calculating the extinction curves and the emission for the typical environments of the Milky Way (MW) and the Large and Small Magellanic Clouds (LMC and SMC) and by comparing the results with the observational data. The final model we have adopted is an hybrid one which stems from combining the analysis of Guhathakurta & Draine (1989) for the emission of graphite and silicates and Puget et al. (1985) for the PAH emission, and using the distribution law of Weingartner & Draine (2001a) and the ionization model for PAHs of Weingartner & Draine (2001b). We apply the model to calculate the spectral energy distribution (SED) of Single Stellar Populations (SSPs) of different age and chemical composition, which may be severely affected by dust at least in two types of star: the young, massive stars while they are still embedded in their parental MCs and the intermediate- and low-mass AGB stars when they form their own dust shell around (see Piovan et al. 2003, for more details about AGB stars). We use the ”Ray Tracing” method to solve the problem of radiative transfer and to calculate extended libraries of SSP SEDs. Particular care is paid to model the contribution from PAHs, introducing different abundances of C in the population of very small carbonaceous grains (VSGs) and different ionization states in PAHs. The SEDs of young SSPs are then compared with observational data of star forming regions of four local galaxies successfully reproducing their SEDs from the UV-optical regions to the mid and far infrared (MIR and FIR, respectively).
Heterogeneity and change in environmental strategy: Technological and political responses to climate change in the global automobile industry

The formulation of strategy is generally treated as a rational process of matching corporate capabilities to market demands. But this does not always account well for the heterogeneity observed in corporate strategies toward complex environmental issues such as climate change. In this chapter, we propose that strategy is often developed in light of expectations and assumptions concerning a firm's internal competencies and the external market and nonmarket environments. These expectations, we propose, are shaped by institutional forces at multiple levels, including the firm, the national industry, the global industry, and the specific environmental issue. In particular, we argue that collective interpretations about the nature of and solutions to climate change constitute important drivers of strategy, and these collective interpretations are molded and contested within institutional fields. In addition to providing a fresh perspective on corporate environmental strategy, this chapter makes a number of contributions to institutional theory. First, we reject a strict dichotomy between the influence of the institutional environment and the competitive environment, as corporate perceptions of market trends are themselves subject to institutional construction. Second, we argue that tensions and political contestation across the complex terrain of interpenetrating and nested fields give rise to heterogeneity and change as integral features of institutional fields rather than difficulties to be explained away. Finally, we suggest that
Attention deficit/hyperactivity disorder (ADHD) symptoms and digit ratios in a college sample

Diagnosticians recognize three subtypes of attention deficit/hyperactivity disorder (ADHD) if there are developmentally inappropriate levels (six or more symptoms) of Hyperactive‐Impulsive behavior, or Inattentive behavior, or both (Combined), respectively. ADHD may partly reflect androgen dysfunction, and an arguable proxy for prenatal androgen exposure is the 2D:4D finger ratio set at least as early as week 9 in the fetus; this is lower in men than in women. We examined the relationship between digit ratios and ADHD symptoms representing the three phenotypes: ADHD/Combined as measured by “summarized” (Rasched) scales, i.e., 1) the short version of the Wender Utah Rating Scale (WURS) and a total symptom list derived from the DSM IV, and the subdivided DSM IV into 2) ADHD/Inattentive and 3) ADHD/Hyperactive‐Impulsive inventories, in a sample of European‐descent college students (135 female, 52 male) not selected for ADHD. All digit ratios were calculated excluding the thumb. There were significant sex differences for the 2D:4D digit ratios of both hands (RH and LH), and between the RH 3D:4D and between the LH 2D:3D ratio. In females, the more masculine the LH 2D:4D ratio, the more the ADHD/Combined symptoms (both WURS and DSM) and the more the ADHD/Inattentive symptoms and ADHD/Hyperactive‐Impulsive symptoms. More masculine ratios also correlated between the total WURS and RH 2D:3D, RH 2D:4D, and LH 2D:3D; and between the inattentive DSM symptoms and LH 2D:5D, and between the ADHD/Hyperactive and Impulsive symptoms and RH 3D:4D. Am. J. Hum. Biol. 19:41–50, 2007. © 2006 Wiley‐Liss, Inc.
party : A Laboratory for Recursive Partytioning

The party package (Hothorn, Hornik, and Zeileis 2006) aims at providing a recursive part(y)itioning laboratory assembling various high- and low-level tools for building tree-based regression and classiﬁcation models. This includes conditional inference trees ( ctree ), conditional inference forests ( cforest ) and parametric model trees ( mob ). At the core of the package is ctree , an implementation of conditional inference trees which embed tree-structured regression models into a well deﬁned theory of conditional inference procedures. This non-parametric class of regression trees is applicable to all kinds of regression problems, including nominal, ordinal, numeric, censored as well as multivariate response variables and arbitrary measurement scales of the covariates. This vignette comprises a practical guide to exploiting the ﬂexible and extensible computational tools in party for ﬁtting and visualizing conditional inference trees.
Conscious Sedation versus General Anesthesia during Endovascular Acute Ischemic Stroke Treatment: A Systematic Review and Meta-Analysis

Nine studies encompassing nearly 2000 patients treated with or without anesthesia for acute stroke were analyzed. Patients with acute ischemic stroke undergoing intra-arterial therapy may have worse outcomes with general anesthesia compared with conscious sedation. However, the difference in stroke severity at the onset may confound the comparison in the available studies. BACKGROUND AND PURPOSE: A number of studies have suggested that anesthesia type (conscious sedation versus general anesthesia) during intra-arterial treatment for acute ischemic stroke has implications for patient outcomes. We performed a systematic review and meta-analysis of studies comparing the clinical and angiographic outcomes of the 2 anesthesia types. MATERIALS AND METHODS: In March 2014, we conducted a computerized search of MEDLINE and EMBASE for reports on anesthesia and endovascular treatment of acute ischemic stroke. Using random-effects meta-analysis, we evaluated the following outcomes: recanalization rate, good functional outcome (mRS ≤ 2), asymptomatic and symptomatic intracranial hemorrhage, death, vascular complications, respiratory complications, procedure time, time to groin, and time from symptom onset to recanalization. RESULTS: Nine studies enrolling 1956 patients (814 with general anesthesia and 1142 with conscious sedation) were included. Compared with patients treated by using conscious sedation during stroke intervention, patients undergoing general anesthesia had higher odds of death (OR = 2.59; 95% CI, 1.87–3.58) and respiratory complications (OR = 2.09; 95% CI, 1.36–3.23) and lower odds of good functional outcome (OR = 0.43; 95% CI, 0.35–0.53) and successful angiographic outcome (OR = 0.54; 95% CI, 0.37–0.80). No difference in procedure time (P = .28) was seen between the groups. Preintervention NIHSS scores were available from 6 studies; in those, patients receiving general anesthesia had a higher average NIHSS score. CONCLUSIONS: Patients with acute ischemic stroke undergoing intra-arterial therapy may have worse outcomes with general anesthesia compared with conscious sedation. However, the difference in stroke severity at the onset may confound the comparison in the available studies; thus, a randomized trial is necessary to confirm this association.
Everolimus Is Associated With Less Weight Gain Than Tacrolimus 2 Years After Liver Transplantation: Results of a Randomized Multicenter Study

Background Weight gain early after transplant is a risk factor for posttransplant metabolic syndrome (PTMS), cardiovascular events, and renal insufficiency. The impact of mammalian target of rapamycin inhibition on posttransplant weight gain and the development of PTMS components postliver transplantation were examined in a randomized, controlled study. Methods After a run-in period, patients (N = 719) were randomized at 30 ± 5 days posttransplant in a 1:1:1 ratio to 3 treatment groups: (i) everolimus (EVR) + reduced tacrolimus (TAC) (n = 245); (ii) TAC control (n = 243) or (iii) TAC elimination (n = 231). In this post hoc analysis, weight change at 12 and 24 months was compared between groups. Vital signs, lipids, and laboratory parameters at 12 and 24 months and rates of PTMS were assessed. Results Mean increase in weight from baseline was higher at month 12 in the TAC control arm (8.15 ± 9.27 kg) than in the EVR + reduced TAC (5.88 ± 12.60 kg, P = 0.056) and the TAC elimination arms (4.76 ± 9.94 kg, P = 0.007). At month 24, the TAC control arm displayed a significantly greater weight increase (9.54 ± 10.21 kg) than either the EVR + reduced TAC (6.69 ± 8.37 kg, P = 0.011) or the TAC elimination groups (6.01 ± 9.98 kg, P = 0.024). Rates of PTMS were similar for the EVR + reduced TAC (71.8%), TAC elimination (70.3%) and TAC control (67.4%) arms (P = NS). Conclusions EVR with reduced-exposure TAC attenuated weight gain at 1 and 2 years posttransplant compared with a standard TAC immunosuppression regimen. Rates of PTMS were comparable between EVR-containing and TAC control regimens.