Miracle-dz/UniFAR-FTUs huggingface dataset:
Activation of Hypoxia-inducible Transcription Factor Depends Primarily upon Redox-sensitive Stabilization of Its α Subunit*

Hypoxia-inducible factor 1 (HIF-1) is a heterodimeric transcription factor that is critical for hypoxic induction of a number of physiologically important genes. We present evidence that regulation of HIF-1 activity is primarily determined by the stability of the HIF-1α protein. Both HIF-1α and HIF-1β mRNAs were constitutively expressed in HeLa and Hep3B cells with no significant induction by hypoxia. However, the HIF-1α protein was barely detectable in normoxic cells, even when HIF-1α was overexpressed, but was highly induced in hypoxic cells, whereas HIF-1β protein levels remained constant, regardless of pO2. Hypoxia-induced HIF-1 binding as well as the HIF-1α protein were rapidly and drastically decreased in vivo following an abrupt increase to normal oxygen tension. Moreover, short pre-exposure of cells to hydrogen peroxide selectively prevented hypoxia-induced HIF-1 binding via blocking accumulation of HIF-1α protein, whereas treatment of hypoxic cell extracts with H2O2 had no effect on HIF-1 binding. These observations suggest that an intact redox-dependent signaling pathway is required for destablization of the HIF-1α protein. In hypoxic cell extracts, HIF-1 DNA binding was reversibly abolished by sulfhydryl oxidation. Furthermore, the addition of reduced thioredoxin to cell extracts enhanced HIF-1 DNA binding. Consistent with these results, overexpression of thioredoxin and Ref-1 significantly potentiated hypoxia-induced expression of a reporter construct containing the wild-type HIF-1 binding site. These experiments indicate that activation of HIF-1 involves redox-dependent stabilization of HIF-1α protein.
Self-Concept as a Correlate of Career Choice of Students in Tertiary Institutions in Sokoto State.

The main thrust of this study was to investigate the relationship between self-concept and career choice of students in Post-Secondary Institutions in Sokoto State. The sample consisted of 300 students (140 males and 160 females) deliberately selected from the population of three tertiary institutions in Sokoto State. Sub-scale A of Akinboye\'s Adolescent Personal Data Inventory was used to measure student\'s self-concept. A Self-designed Career Choice Questionnaire was also used to measure students career choice. Three hypotheses were generated in this study and tested with the use of t-test and the Pearson Product Movement Correlation Coefficient. The major findings of the study were that: there was no significant difference between sex of students and their self-concept; there was significant difference in the career choice of male and female students; and there was a high positive and significant relationship between students\' self-concept and their career choice. The results were discussed and their implications highlighted. It was recommended that teachers should help and encourage students to develop favourable and positive self concept through the use of self-concept enhancing strategies like positive thinking, self-reinforcement and feedback. The Nigerian Journal Of Guidance And Counselling Vol. 7 (1) 2000: pp. 1-11
Graph Based Similarity Measures for Synonym Extraction from Parsed Text

We learn graph-based similarity measures for the task of extracting word synonyms from a corpus of parsed text. A constrained graph walk variant that has been successfully applied in the past in similar settings is shown to outperform a state-of-the-art syntactic vector-based approach on this task. Further, we show that learning specialized similarity measures for different word types is advantageous.
At Home in the Seamless Web

Political responses to metropolitan growth in the United States and elsewhere should include careful ethical deliberation, but ethical judgment and action are limited by the involvement of individual moral agents in the complex processes that give shape to the built environment. I propose that casting the built environment as a heterogeneous sociotechnical ensemble can provide useful insight into the limits of ethics, particularly through the concept of obduracy. To the extent components of an ensemble are obdurate, they can stop or deflect even well-considered actions even as they impose constraints on moral agency itself. From this possibility spring a number of worthwhile lines of inquiry at the confluence of ethics and technology studies.
Realistic neural nets need to learn iconic representations

s Connectionist models provide a promising alternative to the traditional computational approach that has for several decades dominated cognitive science and artificial intelligence, although the nature of connectionist models and their relation to symbol processing remains controversial. Connectionist models can be characterized by three general computational features: distinct layers of interconnected units, recursive rules for updating the strengths of the connections during learning, and "simple" homogeneous computing elements. Using just these three features one can construct surprisingly elegant and powerful models of memory, perception, motor control, categorization, and reasoning. What makes the connectionist approach unique is not its variety of representational possibilities (including "distributed representations") or its departure from explicit rule-based models, or even its preoccupation with the brain metaphor. Rather, it is that connectionist models can be used to explore systematically the complex interaction between learning and representation, as we try to demonstrate through the analysis of several large networks.
Semi‐automatic surface and volume mesh generation for subject‐specific biomedical geometries

An overview of surface and volume mesh generation techniques for creating valid meshes to carry out biomedical flows is provided. The methods presented are designed for robust numerical modelling of biofluid flow through subject‐specific geometries. The applications of interest are haemodynamics in blood vessels and air flow in upper human respiratory tract. The methods described are designed to minimize distortion to a given domain boundary. They are also designed to generate a triangular surface mesh first and then volume mesh (tetrahedrons) with high quality surface and volume elements. For blood flow applications, a simple procedure to generate a boundary layer mesh is also described. The methods described here are semi‐automatic in nature because of the fact that the geometries are complex, and automation of the procedures may be possible if high quality scans are used. Copyright © 2011 John Wiley & Sons, Ltd.
Perceived Control and the Development of Coping

Perceived control is a powerful resource when dealing with stressful life events. Research on perceived control (in all its guises, including locus of control, self-effi cacy, causal attributions, confi dence, and perceived competence) documents its role in supporting constructive mastery-oriented coping at all points in the lifespan. Likewise, research at every age reveals the vulnerabilities induced by a sense of helplessness and loss of control, and documents their effects in undermining how people deal with diffi culties and failures. This chapter uses work on the development of perceived control to help guide the developmental study of coping, examining (1) how mastery-oriented and helpless ways of coping may change in their form across infancy, childhood, adolescence, adulthood, and old age; (2) how the development of perceived control may contribute to qualitative shifts in how coping is organized as people age; and (3) how coping itself may constitute a proximal process that shapes the development of perceived control. Throughout the chapter, a multi-level systems view on the development of coping is highlighted, with a strong emphasis on the role of social partners, relationships, and contexts in shaping both coping and perceived control.
Retrospective Studies with Inconsistent Data: Results, Conclusions and Recommendations should be taken with a Grain of Salt

Gastroesophageal varices are present in about 50% of cirrhotic patients, with a 40% prevalence rate in Child Pugh (CP) class A cirrhotic patients and 85% among CP class C patients. Variceal hemorrhage occurs at a yearly rate of 5-15%, and the most important predictor for bleeding is the size of the varices, the presence of red wales, and decompensated cirrhosis. [1] The management of variceal hemorrhage has greatly improved in the past two decades, with mortality rates reducing from 40% in earlier studies to 10-15% in more recent studies. [1] This is due to an improvement in the general management of these patients and the utility of endoscopic band ligation (EBL) to arrest bleeding. EBL has replaced sclerotherapy which was associated with high rebleeding and complications rates, and required more endoscopic sessions for variceal eradication. [1] The improvement in outcome is also attributed to the advances made in liver transplantation thereby serving to salvage patients and prevent future rebleeding episodes, particularly in advanced CP class C cirrhotic patients. Finally, prophylactic antibiotic usage, including intravenous erythromycin prior to endoscopy for better mucosal visualization,[2] advances in endoscopic techniques, and the introduction of trans-jugular portosystemic shunts (TIPS) have also contributed to the overall improved outcome.
Performance-aware flight path planning for unmanned aircraft in uniform wind fields

We present an approach to efficiently plan flight paths for unmanned fixed-wing aircraft in uniform wind fields. Time-optimal parametric paths are constructed from segments that correspond to stationary flight conditions and may fully utilize the aircraft's performance limits. We provide the tools to analytically derive safety margins for flight performance limits required to compensate for systematic or estimated errors. Our approach adapts recent techniques to use trochoids for horizontal path planning in uniform wind fields and uses superposition of parametric curves to obtain three-dimensional flight paths. We have integrated our approach with a roadmap-based global path planner to demonstrate its applicability to complex mission scenarios. Finally, we present comparative closed-loop simulation results indicating that a significant gain in mission performance can be achieved by accounting for the prevailing wind direction.
The role of the thymus in HIV infection: a 10 year perspective

Despite substantial progress over the last 10 years the exact role of the thymus in HIV-1 infection and HIV-1 pathogenesis is still under investigation. Much has been learned of the types of cells in the thymus that are targets for CXCR4 and CCR5 HIV-1 isolates. In addition, it has become clear that even the adult thymus continues to function, although at a much lower level in uninfected patients, and is able to export naive T cells to the periphery. Changes in thymus function can be evaluated by several methods, including determination of naive T-cell subsets using multicolor flow cytometry and T-cell receptor excision circles (TREC), as well as thymus size and metabolic labeling assays [1–5]. Although each of these measures has its advantages and drawbacks [6], combinations of these parameters provide a picture of the contribution of thymic output and homeostatic proliferative expansion (HPE) to peripheral blood T-cell homeostasis. The importance of the thymus in regenerating a functional immune system has been clearly shown after chemotherapy, bone marrow transplantation and highly active retroviral therapy (HAART) in HIV infection [5,7–10]. The data published during the last 10 years also show that a possible increase in thymic output has an instrumental role in the immunopathogenesis that takes place during the clinically asymptomatic phase of HIV-1 infection.
Identification of Novel Genes Involved in Congenital Hypothyroidism Using Serial Analysis of Gene Expression

Part of the molecular basis of congenital hypothyroidism (CH) has been elucidated by the identification of molecular defects in pituitary- and thyroid-specific genes in patients with various subtypes of hypothyroidism. So far identified genetic defects only explain a small proportion of cases of hypothyroidism. Thus novel research strategies are required to isolate more tissue-specific genes involved in the pathogenesis of CH at present considered ‘idiopathic’ from a molecular perspective. We applied serial analysis of gene expression to human thyroid tissue and developed a computational substraction method to identify tissue-specific genes. The result has been the identification of three genes preferentially expressed in the thyroid gland. The first one encodes part of the thyroid oxidase (THOX2) system. We linked mutations in the THOX2 gene with idiopathic cases of transient and permanent CH. The second transcript identified, DEHAL1, encodes the protein responsible for the recycling of iodine in the thyroid gland and represents the candidate gene for a specific subtype of CH. The third one encodes NM41, a protein currently under investigation which shows features characteristic of the cystine-knot family of proteins, typically involved in early development.
The scheme of subordinate tenures of land in Ghana

The law of Ghana has for more than a century consisted of three types of law: Ghanaian and English statutory enactments, Ghanaian customary law, and common law. Each of these sources has affected the system of land tenure, which as a result is unusually complex. This article aims to summarize the present position in respect of subordinate tenures. It will not examine the customary law allodial title to land, since that in itself would need a discussion as lengthy as the present one. The sources primarily relied upon are those regarded as authoritative by the courts: judicial decisions and certain textbooks. In addition, factual evidence has been derived from other writings.
Appraising Emotion Work

In an era when greater responsiveness is required of government workers, the authors test whether there is a blind spot in employee performance appraisals that prevents rewarding the most effective workers. Emotional labor—work that is relational and involves the manipulation and expression of emotions—is labor intensive and is required of many public service workers if they are to perform their jobs well. The authors hypothesize that rationality, or “left brain” work, remains privileged whereas relational work remains marginalized and unrewarded. To investigate whether there is a disconnect between the required performance of emotional labor and annual appraisals that acknowledge its performance, the authors review appraisal instruments used by public agencies in Illinois. Results confirm that 86% of the instruments identify the performance of emotion work at only a perfunctory level or lower. The lack of acknowledgement renders such labor invisible and contributes to depressed wages of those whose jobs require it.
Antitumor Activity of Sphingosine Kinase Inhibitors

Sphingosine kinase (SK) is an oncogenic sphingolipid-metabolizing enzyme that catalyzes the formation of the mitogenic second messenger sphingosine-1-phosphate (S1P) at the expense of proapoptotic ceramide. Thus, SK is an attractive target for cancer therapy because blockage of S1P formation leads to inhibition of proliferation, as well as the induction of apoptosis in cancer cells. We have recently identified novel SK inhibitors with nanomolar to low micromolar potencies toward recombinant human SK. This study describes the continuing analysis of these inhibitors through in vitro and in vivo experiments. All three structurally diverse SK inhibitors tested showed antitumor activity in mice without exhibiting toxicity. Blood and tumor inhibitor concentrations exceeded in vitro potency levels. Cell signaling analyses in vitro revealed mixed inhibition of mitogen-activated protein kinase kinase and Akt phosphorylation by the SK inhibitors. Importantly, 4-[4-(4-chloro-phenyl)-thiazol-2-ylamino]-phenol (SKI-II) is orally bioavailable, detected in the blood for at least 8 h, and showed a significant inhibition of tumor growth in mice. These compounds are the first examples of nonlipid selective inhibitors of SK with in vivo antitumor activity and provide leads for further development of inhibitors of this important molecular target.
Cardiovascular Autonomic Neuropathy and Subclinical Cardiovascular Disease in Normoalbuminuric Type 1 Diabetic Patients

Cardiovascular autonomic neuropathy (CAN) is associated with increased mortality in diabetes. Since CAN often develops in parallel with diabetic nephropathy as a confounder, we aimed to investigate the isolated impact of CAN on cardiovascular disease in normoalbuminuric patients. Fifty-six normoalbuminuric, type 1 diabetic patients were divided into 26 with (+) and 30 without (−) CAN according to tests of their autonomic nerve function. Coronary artery plaque burden and coronary artery calcium score (CACS) were evaluated using computed tomography. Left ventricular function was evaluated using echocardiography. Blood pressure and electrocardiography were recorded through 24 h to evaluate nocturnal drop in blood pressure (dipping) and pulse pressure. In patients +CAN compared with −CAN, the CACS was higher, and only patients +CAN had a CACS >400. A trend toward a higher prevalence of coronary plaques and flow-limiting stenosis in patients +CAN was nonsignificant. In patients +CAN, left ventricular function was decreased in both diastole and systole, nondipping was more prevalent, and pulse pressure was increased compared with −CAN. In multivariable analysis, CAN was independently associated with increased CACS, subclinical left ventricular dysfunction, and increased pulse pressure. In conclusion, CAN in normoalbuminuric type 1 diabetic patients is associated with distinct signs of subclinical cardiovascular disease.
Private pensions for Europe

Private pensions can enhance international and intergenerational risk-sharing and create a deeper European capital market, which allows for better diversification of country-specific risks and facilitates economic growth. Private funding of pensions creates a more integrated European capital market and internal market for pension services. Pension funds should embrace risks in order to be able to build good pensions at reasonable costs. EU regulation of pension funds should therefore not focus on requirements to guarantee safe pensions, but rather should stimulate funds to share risks efficiently among participants and mandate funds to communicate risks transparently to individuals. Mandatory participation in stand-alone pension funds can provide the necessary commitment for better intergenerational risk-sharing. These stand-alone funds can play an important role also as trusted partners for financially illiterate consumers. The scale and type of collectives vary with the specific institutional setting of each European country. To facilitate tailormade solutions for market imperfections and behavioural issues, the EU should allow for mandatory participation and other constraints on free competition in the market for pensions.
Evaluation of Weight Loss Over Time in Cats with Chronic Kidney Disease

Background Thin body condition and weight loss are common in cats with chronic kidney disease (CKD). However, the time course and progression of weight loss before and after diagnosis have not been thoroughly evaluated. Hypothesis/Objectives To describe weight loss in cats with CKD before and after diagnosis and its relationship to survival. Animals A total of 569 cats (55.5% females and 44.5% males) with CKD from 6 US veterinary practices for which International Renal Interest Society (IRIS) stage, age, date of CKD diagnosis, and at least two body weight measurements were available. Methods Body weight measurements were analyzed by time windows and polynomial growth curve analysis. Survival analysis was performed by Kaplan–Meier curves and log‐rank tests. Results Median age at diagnosis was 14.9 years (range, 5.0–22.8 years). Cats were categorized at diagnosis as IRIS stage 1 (n = 34 [6%]), stage 2 (n = 345 [61%]), stage 3 (n = 141 [25%]), and stage 4 (n = 49 [9%]). Median body weight at diagnosis was 4.2 kg (range, 1.6–9.9 kg). Cats lost a median of 8.9% of body weight in the 12 months before diagnosis, but weight loss was already present 3 years before diagnosis and accelerated after diagnosis of CKD. Cats <4.2 kg at the time of diagnosis had significantly shorter survival time compared to cats ≥ 4.2 kg at diagnosis (P < .0001). Conclusions and Clinical Importance Weight loss can be detected in cats before diagnosis of CKD, accelerates after diagnosis, and is associated with shorter survival. Tracking body weight may help clinicians in earlier diagnosis of CKD.
Physician and Practice Characteristics are Associated With Adherence to Evidence-Based Guidelines for Depressive and Anxiety Disorders ?

Background: Research on quality of care for depressive and anxiety disorders has reported low rates of adherence to evidence-based depression and anxiety guidelines. To improve this care, we need a better understanding of the factors determining guideline adherence. Objective: To investigate how practiceand professional-related factors are associated with adherence to these guidelines. Design: Cross-sectional cohort study. Participants: A total of 665 patients with a composite interview diagnostic instrument diagnosis of depressive or anxiety disorders, and 62 general practitioners from 21 practices participated. Measures: Actual care data were derived from electronic medical record data. The measurement of guideline adherence was based on performance indicators derived from evidence-based guidelines. Practice-, professional-, and patient-related characteristics were measured with questionnaires. The characteristics associated with guideline adherence were assessed by multivariate multilevel regression analysis. Results: A number of practice and professional characteristics showed a significant univariate association with guideline adherence. The multivariate multilevel analyses revealed that, after controlling for patient characteristics, higher rates of guideline adherence were associated with stronger confidence in depression identification, less perceived time limitations, and less perceived barriers for guideline implementation. These professional-related determinants differed among the overall concept of guideline adherence and the various treatment options. Conclusions: This study showed that rates of adherence to guidelines on depressive and anxiety disorders were not associated with practice characteristics, but to some extent with physician characteristics. Although most of the identified professional-related determinants are very difficult to change, our results give some directions for improving depression and anxiety care.