Miracle-dz/UniFAR-FTUs huggingface dataset:
Thyroid hormone-induced oxidative damage on lipids, glutathione and DNA in the mouse heart

Oxygen radicals of mitochondrial origin are involved in oxidative damage. In order to analyze the possible relationship between metabolic rate, oxidative stress and oxidative damage, OF1 female mice were rendered hyper- and hypothyroid by chronic administration of 0.0012% L-thyroxine (T4) and 0.05% 6-n-propyl-2-thiouracil (PTU), respectively, in their drinking water for 5 weeks. Hyperthyroidism significantly increased the sensitivity to lipid peroxidation in the heart, although the endogenous levels of lipid peroxidation were not altered. Thyroid hormone-induced oxidative stress also resulted in higher levels of GSSG and GSSG/GSH ratio. Oxidative damage to mitochondrial DNA was greater than that to genomic DNA. Hyperthyroidism decreased oxidative damage to genomic DNA. Hypothyroidism did not modify oxidative damage in the lipid fraction but significantly decreased GSSG and GSSG/GSH ratio and oxidative damage to mitochondrial DNA. These results indicate that thyroid hormones modulate oxidative damage to lipids and DNA, and cellular redox potential in the mouse heart. A higher oxidative stress in the hyperthyroid group is presumably neutralized in the case of nuclear DNA by an increase in repair activity, thus protecting this key molecule. Treatment with PTU, a thyroid hormone inhibitor, reduced oxidative damage in the different cell compartments.
Ownership and Changes in Hospital Inefficiency, 1986–1991

This study examines how ownership affected changes in hospital inefficiency after the introduction of prospective payment by Medicare. Using a national data set, we estimate cost frontiers for 1986 and 1991 to assess hospitals' efficiency relative to best practice in both those years. We then use regression analysis to determine the effect of ownership on the change in hospitals' efficiency. The results indicate that, in both 1986 and 1991, mean inefficiency was highest for for-profit hospitals and lowest for not-for-profit hospitals, with government hospitals falling in the middle. Moreover, between 1986 and 1991, both for-profit and government hospitals had significantly less improvement in efficiency than not-for-profit hospitals, all else equal.
A network theory of the immune system

The face that every antibody also had antigenic properties leads to the existence of a functional network of interacting antibodies and lymphocytes in the immune system. With a minimum set of assumptions about thenature of these interactions some of the principal features of the immune response such as normal primary and secondary response, low and highzone tolerance induction, and memory can be reproduced. The low zone tolerance phenomenon plays a central role in our theory, as it is the simplest nontrivial mode of response to an antigenic stimulus. It may be understood as the defeat of the stimulated lymphocyte species against their internal adversaries. The normal response and high zone tolerance induction may be characterized as low zone tolerance on a second and third level of a hierarchy of lymphocyte populations. In particular, the weakness of the primary response in explained in terms of internal struggles whichlead to a final suppression of the aggressors, thereby opening the way for an unhindered secondary response.
Motivation To Play Esports: Case of League of Legends

The population of playing electronic sports has increased recently, and the most popular one is League of Legends (LoL). As a multiplayer online battle arena video game, it’s not only a game, but also a competitive electronic sport. The purpose of this study was to assess the motivations of playing League of Legends and to relate them by genders, age groups and frequency groups. The final sample comprised 111 LoL players. The study categorized 12 items into three factors: achievement, socialization and immersion. Results indicated that achievement factors were stronger motives for men than women. For different age groups, there was no significant difference on socialization factors. The immersion factors for players who spent different times on LoL were not very influential.
Synucleins Regulate the Kinetics of Synaptic Vesicle Endocytosis

Genetic and pathological studies link α-synuclein to the etiology of Parkinson's disease (PD), but the normal function of this presynaptic protein remains unknown. α-Synuclein, an acidic lipid binding protein, shares high sequence identity with β- and γ-synuclein. Previous studies have implicated synucleins in synaptic vesicle (SV) trafficking, although the precise site of synuclein action continues to be unclear. Here we show, using optical imaging, electron microscopy, and slice electrophysiology, that synucleins are required for the fast kinetics of SV endocytosis. Slowed endocytosis observed in synuclein null cultures can be rescued by individually expressing mouse α-, β-, or γ-synuclein, indicating they are functionally redundant. Through comparisons to dynamin knock-out synapses and biochemical experiments, we suggest that synucleins act at early steps of SV endocytosis. Our results categorize α-synuclein with other familial PD genes known to regulate SV endocytosis, implicating this pathway in PD.
Determinants of entrepreneurial intentions: An institutional embeddedness perspective

A more nuanced understanding of the entrepreneurial intentions of individuals seems improbable without exploring the intricate interplay between individuals and the institutional context in which they are embedded. Accordingly, not only does this paper contribute to the paucity of studies that explore the multiple facets of institutional context in shaping entrepreneurial intentions, but it also further advances the current institutional approach by testing the ‘situational configuration’ of institutional and personal factors in the context of a developing country like Pakistan. To examine the influence of a multitude of institutional factors in a sequential way, a nested model was used. The findings revealed that the educational context in which students are embedded play a pivotal role in mitigating any adverse impact that their negative perceptions regarding the structural environment that surrounds them might have on their entrepreneurial intentions. These findings have important implications for educators and policy-makers alike.
Organizational Boundaries in Fluid Forms of Production: The Case of Apache Open-source Software

Abstract This chapter explores the multiplicity, formation, and porosity of organizational boundaries in new, fluid forms of production. Conceptualizing them as “partial organizations,” we argue that both the intentional design of organizational elements (such as membership, hierarchy, rules, monitoring, and sanctioning) as well as unintended adjustments of “unorganized” aspects drive boundary formation and impact boundary porosity. In addition, we contend that structuring dynamics will create specific trajectories for boundaries over time. Empirically, we further our theoretical framework on the basis of an in-depth case study of the Apache open-source software community during its formative years (1995–2002). We find that both the salience and formalization of boundaries increase over time. However, different conceptions of boundaries (such as efficiency, competence, power, and identity) become salient at different points in time. While design and adjustment drive boundary formation with regard to all boundary conceptions in our empirical case, porosity develops differently for each of them. We also demonstrate that the formalization of boundaries does not necessarily reduce boundary porosity, but actually may increase it.
Population pharmacokinetic/pharmacodynamic analysis of CCR5 receptor occupancy by maraviroc in healthy subjects and HIV-positive patients.

BACKGROUND Maraviroc, a noncompetitive antagonist of the CCR5 coreceptor, was recently approved in the USA as a treatment of HIV infection. For antiretroviral agents that target the virus, antiviral effect can be related to some extent to plasma drug concentrations. For CCR5 antagonists that target the host cells, receptor occupancy in vivo might be a better predictor of efficacy. AIMS To develop a population pharmacokinetic (PK)-pharmacodynamic (PD) model that describes CCR5 receptor occupancy by maraviroc after oral administration at different doses in healthy volunteers and HIV-positive patients and to assess the relevance of receptor occupancy in predicting the decrease in viral load (HIV-1 RNA copies ml(-1)) in HIV-positive patients. METHODS Receptor occupancy data from 88 individuals enrolled in two multiple dose trials were included in the population PK-receptor binding model. Out of the 88 individuals, 25 were HIV-1-infected patients and had viral load measurements, whereas the remaining 63 were healthy volunteers. Doses ranged from 3 mg b.i. d. to 600 mg q.d. A previously published PK-PD disease model describing the effect of maraviroc on the viral load was updated by replacing its PD module by the receptor occupancy model. Simulated viral load-time profiles with the updated model were compared with the profiles observed in patients. RESULTS The majority of measured plasma concentrations were associated with receptor occupancy > or = 50% even at the lowest dose of 3 mg b.i. d. A simple direct E(max) model appeared to describe satisfactorily the PK-receptor occupancy relationship. The estimated K(D) was around 0.0894 ng ml(-1), far below the operational in vivo antiviral IC(50) of 8 ng ml(-1). Accordingly, simulations led to marked overprediction of the decrease in viral load-time profiles. CONCLUSIONS Maraviroc receptor occupancy close to the maximum is required to induce a significant decrease in viral load, indicating that in vivo CCR5 receptor occupancy by maraviroc is not a direct measure of drug inhibitory activity. Considering the imprecision of the measurement in the upper flat part of the maraviroc concentration vs. percent CCR5 occupancy curve, it can reasonably be concluded that routine monitoring of receptor occupancy as a biomarker for maraviroc efficacy will not be helpful. Based on this analysis, it was decided not to use receptor occupancy as a biomarker of viral load inhibition during the development of CCR5 antagonist compounds.
Middle School Teacher Collaboration: The Intersection of Teacher Domain and Administrative Purview

This study examined the experiences and perspectives of twelve urban public middle school teachers and one focused instructional coach in one district in a New England state involved in a district-mandated change to professional learning communities as their form of teacher collaboration. It explored teachers’ reasons for engaging in collaboration, their understanding of the administration’s expectations for their collaboration, the factors and conditions that influenced their collaborative work, and the perceived effects of collaboration on their teaching practices and professional identity. This qualitative phenomenological study employed a purposeful sampling strategy and both interviews and field observations to uncover teachers’ perceptions of collaboration. The professional learning community meetings of one team (five teachers and the focused instructional coach at the same school) were observed five times and these six individuals were interviewed twice each. The remaining seven teachers, assigned to collaborative teams at other middle schools in the same district, were each interviewed once. The study found that teachers’ reasons for participating in collaboration vary and are based on both intrinsic and extrinsic motivations. According to participants, they are more receptive to administrative expectations for teacher collaboration that are perceived to be from their principal rather than from the district administration. The study found that although teachers see the good intentions for collaboration to benefit the school community, there are instances of certainty and uncertainty about their own agency in achieving the intended outcomes. The study also found that although some factors and conditions that influence teacher collaboration occur across many school settings, fostering teacher collaboration requires close attention to each school’s particular context, including the presence of a unifying school culture. Lastly, the study found that teachers that value collaboration recognize that it has a positive effect on the development of their MIDDLE SCHOOL TEACHER COLLABORATION xii teaching practices, professional identity, and sense of collective responsibility. The implications of this study for principals involve the need to structure professional learning communities to emphasize their importance to teachers and the need to discover conditions that enable collaborative team members to develop trust in one another. The implications for teachers include the importance of exercising their own judgement about the topics to investigate in their professional learning communities so that the work that they do is meaningful to them. Additional questions about teachers’ perceptions of expectations from the principal as compared to expectations from the district administration as well as the possible connection between a unifying school culture and the effectiveness of teacher collaboration must still be explored.
Concepts and principles of O-linked glycosylation.

The biosynthesis, structures, and functions of O-glycosylation, as a complex posttranslational event, is reviewed and compared for the various types of O-glycans. Mucin-type O-glycosylation is initiated by tissue-specific addition of a GalNAc-residue to a serine or a threonine of the fully folded protein. This event is dependent on the primary, secondary, and tertiary structure of the glycoprotein. Further elongation and termination by specific transferases is highly regulated. We also describe some of the physical and biological properties that O-glycosylation confers on the protein to which the sugars are attached. These include providing the basis for rigid conformations and for protein stability. Clustering of O-glycans in Ser/Thr(/Pro)-rich domains allows glycan determinants such as sialyl Lewis X to be presented as multivalent ligands, essential for functional recognition. An additional level of regulation, imposed by exon shuffling and alternative splicing of mRNA, results in the expression of proteins that differ only by the presence or absence of Ser/Thr(/Pro)-rich domains. These domains may serve as protease-resistant spacers in cell surface glycoproteins. Further biological roles for O-glycosylation discussed include the role of isolated mucin-type O-glycans in recognition events (e.g., during fertilization and in the immune response) and in the modulation of the activity of enzymes and signaling molecules. In some cases, the O-linked oligosaccharides are necessary for glycoprotein expression and processing. In contrast to the more common mucin-type O-glycosylation, some specific types of O-glycosylation, such as the O-linked attachment of fucose and glucose, are sequon dependent. The reversible attachment of O-linked GlcNAc to cytoplasmic and nuclear proteins is thought to play a regulatory role in protein function. The recent development of novel technologies for glycan analysis promises to yield new insights in the factors that determine site occupancy, structure-function relationship, and the contribution of O-linked sugars to physiological and pathological processes. These include diseases where one or more of the O-glycan processing enzymes are aberrantly regulated or deficient, such as HEMPAS and cancer.
Decreased expression of DCC mRNA in human colorectal cancers

The mRNA expression levels of DCC gene, which is cloned from the deleted region of chromosome 18q in colorectal cancers and thought to be a tumor‐suppressor gene, was evaluated in tissue specimens surgically resected from patients with colorectal cancer by RT‐PCR. This method was chosen as the expression level of DCC mRNA is below the detectable level for Northern‐blot analysis. Semi‐quantitative measurements of DCC mRNA were performed based on a standard curve defined by serial dilution of DCC cDNA. As a result, the expression level of DCC mRNA was found to be lower in 17 out of 30 colorectal cancers than in adjacent non‐cancerous tissues. Inclusion of smooth muscle in tissue specimens was observed to have little disturbing effect on comparisons between cancerous and non‐cancerous regions. In addition, all 4 specimens of colorectal cancer with liver metastasis showed the decreased expression level of DCC mRNA, suggesting that functional loss of DCC in cancerous tissues may play an important role in metastatic events.
Exploring the occupational injustices of human trafficking

ABSTRACT Human trafficking is a complex global issue described as modern day slavery, and people who are trafficked can experience severe trauma with long term consequences impacting their health and well-being. Drawing on an occupational perspective, we discuss four case studies from the literature to examine occupational marginalisation, deprivation, imbalance, and alienation. Our analysis shows that across different types of exploitation, in diverse geographical locations, forced occupation and a lack of meaningful occupation, both have a negative impact on health. In addition, we argue that the individual experiences of exploitation reflect collective injustices. Human trafficking is therefore a violation of individual occupational rights, and a social and political issue of occupational injustice. Attention on human trafficking from an occupational perspective appears to have been absent from the occupational science literature.
The influence of anti-TNF therapy upon incidence of keratinocyte skin cancer in patients with rheumatoid arthritis: longitudinal results from the British Society for Rheumatology Biologics Register

Objectives To compare the risk of keratinoctye skin cancer (basal cell carcinoma (BCC) and squamous cell carcinoma (SCC)) in patients treated for rheumatoid arthritis (RA) compared with the general population, and to determine whether anti-tumour necrosis factor (TNF) therapy exacerbates this risk. Methods Patients with RA enrolled in the British Society for Rheumatology Biologics Register, a prospective national cohort established in 2001 to monitor the safety of anti-TNF, were followed until 2008. 11 881 patients treated with anti-TNF were compared with 3629 patients receiving non-biological disease-modifying antirheumatic drugs (nbDMARD). Standardised incidence ratios (SIR) were calculated for each cohort and rates between cohorts were compared using Cox proportional HR, adjusted using inverse probability of treatment weighting. Results SIR for skin cancer was increased in both cohorts compared with the English population: SIR 1.72 (95% CI 1.43 to 2.04) anti-TNF; 1.83 (95% CI 1.30 to 2.50) nbDMARD only. In patients without previous skin cancer, BCC incidence per 100 000 patient-years was 342 (95% CI 290 to 402) after anti-TNF and 407 (95% CI 288 to 558) after nbDMARD. HR after anti-TNF adjusted for treatment weighting was 0.95 (95% CI 0.53 to 1.71). SCC incidence per 100 000 patient-years: anti-TNF 53 (95% CI 33 to 79); nbDMARD 43 (95% CI 12 to 110); adjusted HR 1.16 (95% CI 0.35 to 3.84). Conclusions Skin cancers were increased among treated patients with RA. No evidence was found that anti-TNF therapy exacerbates the risk of BCC or SCC but this cannot be excluded. Patients with RA should use sun protection and be monitored for skin cancer.
Sputum induction for the diagnosis of pulmonary tuberculosis in infants and young children in an urban setting in South Africa

BACKGROUND Bacteriological confirmation of pulmonary tuberculosis is difficult in infants and young children. In adults and older children, sputum induction has been successfully used; this technique has not been tested in younger children. AIMS To investigate whether sputum induction can be successfully performed in infants and young children and to determine the utility of induced sputum compared to gastric lavage (GL) for the diagnosis of pulmonary tuberculosis in HIV infected and uninfected children. SUBJECTS AND METHODS 149 children (median age 9 months) admitted to hospital with acute pneumonia who were known to be HIV infected, suspected to have HIV infection, or required intensive care unit support. Sputum induction was performed on enrolment. Early morning GL was performed after a minimum four hour fast. Induced sputum and stomach contents were stained for acid fast bacilli and cultured for Mycobacterium tuberculosis. RESULTS Sputum induction was successfully performed in 142 of 149 children.M tuberculosis, cultured in 16 children, grew from induced sputum in 15. GL, performed in 142 children, was positive in nine; in eight of these M tuberculosis also grew from induced sputum. The difference between yields from induced sputum compared to GL was 4.3% (p = 0.08). M tuberculosiswas cultured in 10 of 100 HIV infected children compared to six of 42 HIV uninfected children (p = 0.46). CONCLUSION Sputum induction can be safely and effectively performed in infants and young children. Induced sputum provides a satisfactory and more convenient specimen for bacteriological confirmation of pulmonary tuberculosis in HIV infected and uninfected children.
Litigation Risk and Cost Behavior: Evidence from Derivative Lawsuits

This study explores whether managers’ personal litigation risk impacts managerial empire building through the lens of their firms’ cost behavior. Exploiting the staggered adoption of universal demand (UD) laws at the state-level in the U.S., we find a significant decrease in Selling, General & Administrative (SG&A) cost elasticity and a significant increase in SG&A cost asymmetry after the exogenous decrease in managers’ personal litigation risk. These associations are not driven by the pre-adoption trend and are robust to a variety of changes in sample composition. In addition, we find that the effect of UD laws is more pronounced in firms: (1) with lower future value creation potential of SG&A costs; (2) with weaker corporate governance; (3) operating in less competitive product markets; (4) with higher information asymmetry; and (5) with lower ex ante litigation risk. Our findings highlight the importance of shareholders’ litigation rights in curbing managerial empire building and add to the agency explanation for cost behavior.
Novel Scenes Improve Recollection and Recall of Words

Exploring a novel environment can facilitate subsequent hippocampal long-term potentiation in animals. We report a related behavioral enhancement in humans. In two separate experiments, recollection and free recall, both measures of hippocampus-dependent memory formation, were enhanced for words studied after a 5-min exposure to unrelated novel as opposed to familiar images depicting indoor and outdoor scenes. With functional magnetic resonance imaging, the enhancement was predicted by specific activity patterns observed during novelty exposure in parahippocampal and dorsal prefrontal cortices, regions which are known to be linked to attentional orienting to novel stimuli and perceptual processing of scenes. Novelty was also associated with activation of the substantia nigra/ventral tegmental area of the midbrain and the hippocampus, but these activations did not correlate with contextual memory enhancement. These findings indicate remarkable parallels between contextual memory enhancement in humans and existing evidence regarding contextually enhanced hippocampal plasticity in animals. They provide specific behavioral clues to enhancing hippocampus-dependent memory in humans.