Miracle-dz/UniFAR-FTUs huggingface dataset:
The Impact of Immunosuppression on Endothelial Function

Endothelial dysfunction is an early marker for transplant atherosclerosis. Potential mechanisms for allograft endothelial dysfunction include stimulation of alloimmune-dependent pathways, ischemia/reperfusion injury, metabolic alterations, chronic infections, as well as direct endothelial cell activation by immunosuppressive drugs. Thus far, no study has directly compared different immunosuppressive drugs with respect to their potential to modulate endothelial function under normoxic and hypoxic conditions. We examined human microvascular endothelial cells (HMEC-1) in vitro after stimulation with therapeutic concentrations of methylprednisolone (MP), mycophenolic acid (MMF), cyclosporine A (CS), rapamycin (Rapa), and tacrolimus (Tac) to designate the corresponding induction of oxidative stress, apoptosis, metabolic activity, proliferation, endothelin (ET-1) release, and nitric oxide (NO) production. HMEC-1 stimulation with CS, MMF, and Rapa resulted in a stronger induction of oxidative stress compared with MP and Tac. Induction of oxidative stress by immunosuppressives correlated with metabolic activity and apoptosis. Low- and high-dose MMF significantly inhibited cell proliferation under hypoxic conditions, whereas low-dose CS and MP increased endothelial cell proliferation. ET-1 release was significantly elevated by Rapa, Tac, and MP. NO production was significantly enhanced by all immunosuppressive drugs except Tac. Quality and quantity of immunosuppression modify endothelial function and lead to a dose-dependent and oxygenation-state-related endothelial activation. MP and MMF induced minor changes in endothelial function compared with CS, Rapa, and Tac.
Foreign Direct Investment Attractiveness Policy Empirical Study Applied To Tunisian Territory

The objective of this article is to analyse competitiveness factors of the Tunisian territory in terms of ability to attract FDI. Based on Dunning’s eclectic theory, we consider that the decision to undertake FDI abroad is the result of the interaction of Ownership-specific advantages, Location-specific advantages and Internalization advantages. The work that we conducted is mainly a conceptual work and to validate it, we used modelling through structural equations on qualitative data, from foreign companies established in Tunisia during the period 2014-2015. This method allowed us, on the one hand, to introduce into the same model several factors to measure the territorial attractiveness and to identify, on the other hand, the relevance of the policies and strategies followed by the host country.
Identification of potential drugs for Parkinson's disease based on a sub-pathway method

Parkinson's disease (PD) is the second most prevalent neurodegenerative disease in ageing individuals. Current therapeutic regimen suffers from general side effects and a poor efficiency for PD symptoms. The need for development new therapeutic agents for PD is urgent. Here, we aimed to explore the metabolic mechanism of PD and identified potential novel agents for PD by a sub-pathway-based method. By using the GSE7621 microarray data from the GEO database, we first identified the 1226 differentially expressed genes (DEGs) between PD and normal samples. Then we identified 19 significant enriched metabolic sub-pathways, which may involve in development of PD. Finally, by an integrated analysis of PD-involved sub-pathways and drug-affected sub-pathways, we identified 49 novel small molecular drugs capable to target the PD-involved sub-pathways. Our method could not only identify existing drug (apomorphine) for PD, but also predict potentially novel agents (ketoconazole and astemizole), which might have therapeutic effects via targeting some key enzymes in arachidonic acid metabolism. These candidate agents identified by our approach may provide insights into a novel therapy approach for PD.
Diminished auditory mismatch fields in dyslexic adults

Electroencephalographic studies have demonstrated smaller auditory responses to infrequent deviances of speech and nonspeech sounds in dyslexic than normal‐reading subjects. We used a whole‐scalp neuromagnetometer to study selectively reactivity of the auditory cortices to sound deviances in 8 dyslexic and 11 normal‐reading adults. Within a monotonous sequence of 50‐millisecond 1,000Hz binaural tones, tones of 920 and 1,080Hz occurred with 7% probability each. Magnetic mismatch fields, elicited by the stimulus deviances, were diminished in the left hemisphere of the dyslexic subjects. The results indicate deficient change detection in the left auditory cortex of right‐handed dyslexic adults. Ann Neurol 2003
Structure of Escherichia coli dGTP Triphosphohydrolase

Background: The Escherichia coli Dgt enzyme hydrolyzes the important DNA building block dGTP, but the cellular role of this activity is still unclear. Results: The enzyme is shown to be a hexameric structure containing regulatory DNA molecules. Conclusion: DNA mediates the regulation of dGTPase activity in the cell. Significance: This is the first demonstration of regulation of dNTPase by DNA. The Escherichia coli dgt gene encodes a dGTP triphosphohydrolase whose detailed role still remains to be determined. Deletion of dgt creates a mutator phenotype, indicating that the dGTPase has a fidelity role, possibly by affecting the cellular dNTP pool. In the present study, we have investigated the structure of the Dgt protein at 3.1-Å resolution. One of the obtained structures revealed a protein hexamer that contained two molecules of single-stranded DNA. The presence of DNA caused significant conformational changes in the enzyme, including in the catalytic site of the enzyme. Dgt preparations lacking DNA were able to bind single-stranded DNA with high affinity (Kd ∼ 50 nm). DNA binding positively affected the activity of the enzyme: dGTPase activity displayed sigmoidal (cooperative) behavior without DNA but hyperbolic (Michaelis-Menten) kinetics in its presence, consistent with a specific lowering of the apparent Km for dGTP. A mutant Dgt enzyme was also created containing residue changes in the DNA binding cleft. This mutant enzyme, whereas still active, was incapable of DNA binding and could no longer be stimulated by addition of DNA. We also created an E. coli strain containing the mutant dgt gene on the chromosome replacing the wild-type gene. The mutant also displayed a mutator phenotype. Our results provide insight into the allosteric regulation of the enzyme and support a physiologically important role of DNA binding.
Disequilibrium Dynamics of the Monetary Economy: A Micro-Founded Synthesis of the Wicksellian Theory of Cumulative Process and the Keynesian Theory of Effective Demand

The present article is an attempt to reconstruct a macro-dynamic theory of the monetary economy on the basis of the theory of monopolistically competitive firms formulated as a micro-foundation for the decentralized price mechanism. It shows how the micro-founded theorization of the very foundation of Classical economics – the decentralized price mechanism – actually undermines the entire structure of Classical economics. The paper establishes the following propositions. (1) If monopolistically competitive firms are free to adjust their prices, their ex ante expectations for the average price are necessarily falsified by the very aggregate outcome of their own decentralized price decisions unless aggregate demand gap happens to be zero. Once the aggregate demand gap deviates from zero, the firms’ simultaneous attempt to rectify their errors in expectations triggers a Wicksellian cumulative process that drives the average price further away from equilibrium. (2) In contrast, if prices are sticky with an exogenous probability, any value of aggregate demand gap becomes compatible with firms’ simultaneous rational expectations and the economy settles to one of infinitely many globally stable steady-states with Keynesian properties. (3) If the price stickiness itself is endogenized in the sense that each firm optimally balances adjustment costs of changing the price and opportunity costs of not changing the price, the economy exhibits a strong nonlinearity in its dynamical behaviors. As long as the aggregate demand gap remains within a band, the firms are able to enjoy rational expectations and the economy tends to be globally stable. Once, however, the aggregate demand gap jumps out of the band, rational expectations become unattainable again and the economy sets off a globally unstable cumulative process. Moreover, there should be a fundamental regime-change in the ways monetary policy should be conducted between when the aggregate demand gap stays within the band and when it strays out of it. (4) Finally, as long as prices are costly to adjust, the aggregate rate of involuntary unemployment never shrinks to the natural rate, and as long as adjustment costs are lump-sum and higher for price reduction than for price increase, the Phillips curve never loses its negative slope even in the long-run.
Reshaping Academic Practice and Relationships within the Department Of Plant Sciences

At the University of Cambridge, a research and development project concerned with teaching and learning in small-group tutorials has been initiated in Department of Plant Sciences. Known as the Plant Sciences Pedagogy Project, it is part of the Teaching for Learning Network (TfLN), which includes members of the Centre for Applied Research into Educational Technologies (CARET), the Department of Engineering and the Faculty of Classics. Provision of small-group tutorials plays a key role in teaching support for students at the University of Cambridge. However, variation in student experience of tutorial quality was raised as a point of concern in a recent student survey (Cambridge University Students’ Union, 2004). Our research therefore focussed on analysis of the tutorial environment with the aim of finding out how best to support our teaching staff and to influence changes in teaching and learning practices within the Department. The Plant Sciences Pedagogy Project used a number of qualitative and quantitative educational research methods in order to identify key plant sciences specific teaching and learning issues. These methods included practice-value questionnaires, self-efficacy questionnaires, supervision video analysis, student focus groups and supervisor interviews, which were implemented over the course of two academic years. The research findings were used to inform the development of a number of new learning resources which were provided for students within a virtual learning environment (VLE), or in collaborative workshops. The impact of the implementation of these new resources was assessed in order to inform research and development for the next academic year. In this paper, we describe the development of the research conducted in the Department of Plant Sciences and also chart the involvement of embedded researchers in the formation of the TfLN. The research structure is initially described in association with action research methodology but it is argued that the format has developed throughout the formation of TfLN so that it is best aligned with theories of social network analysis (Granovetter, 1973). This paper uses the theoretical perspective of brokerage between communities of practice (Burt, 2005; Wenger, 1998) to describe the role that plant science researchers have played in conducting research concerned with initiating changes in teaching and learning practices and also the subsequent coconfiguration of the TfLN research community. Burt’s (2005) four levels of brokerage are used to structure the discussion of these research processes, and the boundary crossing objects that have been used to support brokerage activities are described.
Involvement of mitochondrial K+ release and cellular efflux in ischemic and apoptotic neuronal death

We measured and manipulated intracellular potassium (K+) fluxes in cultured hippocampal neurons in an effort to understand the involvement of K+ in neuronal death under conditions of ischemia and exposure to apoptotic stimuli. Measurements of the intracellular K+ concentration using the fluorescent probe 1,3‐benzenedicarboxylic acid, 4,4′‐[1,4,10,13‐tetraoxa‐7,16‐diazacyclooctadecane‐7,16‐diylbis(5‐methoxy‐6,2‐benzofurandiyl)]bis‐, tetrakis [(acetyloxy) methyl] ester (PBFI) revealed that exposure of neurons to cyanide (chemical hypoxia), glutamate (excitotoxic insult) or staurosporine (apoptotic stimulus) results in efflux of K+ and cell death. Treatment of neurons with 5‐hydroxydecanoate (5HD), an inhibitor of mitochondrial K+ channels, reduced K+ fluxes in neurons exposed to each insult and increased the resistance of the cells to death. K+ efflux was attenuated, levels of oxyradicals were decreased, mitochondrial membrane potential was stabilized and release of cytochrome c from mitochondria was attenuated in neurons treated with 5HD. K+ was rapidly released into the cytosol from mitochondria when neurons were exposed to the K+ channel opener, diazoxide, or to the mitochondrial uncoupler, carbonyl cyanide 4(trifluoromethoxy)phenylhydrazone (FCCP), demonstrating that the intramitochondrial K+ concentration is greater than the cytosolic K+ concentration. The release of K+ from mitochondria was followed by efflux through plasma membrane K+ channels. In vivo studies showed that 5HD reduces ischemic brain damage without affecting cerebral blood flow in a mouse model of focal ischemic stroke. These findings suggest that intracellular K+ fluxes play a key role in modulating neuronal oxyradical production and cell survival under ischemic conditions, and that agents that modify K+ fluxes may have therapeutic benefit in stroke and related neurodegenerative conditions.
[Clozapine-associated neuroleptic malignant syndrome followed by catatonia: a case report].

OBJECTIVE Neuroleptic malignant syndrome (NMS) is a rare life-threatening condition associated with the use of antipsychotics and other drugs that influence dopaminergic transmission. Although NMS is typically associated with classical antipsychotics, it can also be induced by atypical antipsychotics. In this paper, we report a case of NMS associated with clozapine use. CASE A 27-year-old male was diagnosed as schizophrenia in 2006 and zuclopenthixol depot was administered parenterally. Following the second injection, NMS was diagnosed and he was switched to clozapine. After 4 years of clozapine use, one day, he suddenly stopped eating, stayed in bed all day, and had incontinence. Upon examination at our hospital the patient had muscle rigidity, high fever, leukocytosis, and a high creatine phosphokinase level, and NMS was diagnosed. He was put on bromocriptine. NMS resolved, but psychotic relapse and catatonia developed. 10 sessions of electro convulsive treatment (ECT) were administered. Quetiapine 25 mg/day was introduced and titrated up to 600 mg/day afterwards. He has been using quetiapine 600 mg/day for 18 months and at the time this manuscript was written has not had any signs of psychosis or NMS. CONCLUSION NMS is usually induced by the use of agents with high dopaminergic affinity. Incomplete or extraordinary NMS cases have been reported due to clozapine and atypical antipsychotics. The presented case is noteworthy due to the complete and typical presentation of NMS. It should always be kept in mind that all atypical antipsychotics including clozapine have the probability to induce NMS although not common.
Stretchable Electronics Technology for Large Area Applications: Fabrication and Mechanical Characterization

The development and mechanical characterization of a novel technology for stretchable electronics is presented, which can be used for the realization of wearable textile electronics and biomedical implants. The stretchable devices consist of rigid or flexible component islands interconnected with stretchable meander-shaped copper conductors embedded in a stretchable polymer, polydemethylsiloxane. The technology uses standard printed circuit board manufacturing steps and liquid injection molding techniques to achieve a robust and reliable product. The conductors in the device are designed to accommodate strains up to 10-15%. Spin-on photo-definable polyimide as mechanical support for the stretchable interconnects and the functional flexible islands are introduced. By use of polyimide, the reliability of the stretchable interconnects, the straight interconnects on the flexible islands and the transitions between the stretchable and nonstretchable parts are improved. Long-term endurance behavior of the stretchable interconnects is studied by cyclic elongation at strain ranges of up to 20% while monitoring the electrical connectivity. It's shown that the lifetime of the polyimide supported interconnects is at least two times better compared to the nonsupported.
Adjusted intraclass correlation coefficients for binary data: methods and estimates from a cluster-randomized trial in primary care

Background Accurate estimates of the intraclass correlation coefficient (ICC) are important for calculating appropriate sample sizes for cluster-randomized trials. The ICC and hence the sample size may be reduced through adjustment for baseline covariates. A method exists for calculating adjusted ICCs for binary outcomes based on the logit link, used to calculate odds ratios. Recent interest in presenting relative risks rather than odds ratios indicates that a method based on the log link is needed. Purpose To determine and evaluate a method for calculating adjusted ICCs based on the log link, and to provide and compare unadjusted and adjusted ICCs from a cluster-randomized trial in primary care based on the logit and log link. Methods Two methods are proposed for calculating adjusted ICCs for the log link based on a first-order Taylor series expansion and properties of the lognormal distribution. The methods are evaluated by simulation. Unadjusted and adjusted ICCs are calculated for binary outcomes from the Point of Care Testing (PoCT) Trial using the logit and log link. Results The methods for calculating adjusted ICCs for the log link produced similar results unless the between cluster variance was large. Unadjusted ICCs for the PoCT Trial ranged from 0.001 to 0.048. The impact of adjustment on the ICC varied between outcomes and link functions, ranging from a 59% reduction to an 89% increase. Limitations The true ICC was unknown for the simulation study. Adjustment was made for age and gender only for the PoCT Trial. Conclusions The method for calculating adjusted ICCs for binary outcomes depends on the link function. For the log link, the method based on the lognormal distribution is recommended. This method will be useful for cluster-randomized trials where the relative risk, rather than the odds ratio, is the effect measure of interest.
The Distribution of Betas in Presence of Nontraded Assets

This study considers a capital assets pricing model (CAPM) in an incomplete financial market wherein not all risky assets are traded and the risk from non‐traded assets is not orthogonal to that of the existing or traded assets. The model shows the extent of the divergence of the CAPM betas (true betas) from the traditional CAPM betas (perceived betas) in market equilibrium conditions in an incomplete market. Specifically, it implies that the more incomplete a financial market is, the wider is the discrepancy between the true and perceived betas, and the distribution of the perceived betas tends to centre more around 1 in an incomplete market than that of true betas. Empirical evidence in various settings support these results.
Effects of salinity levels on proteome of Suaeda aegyptiaca leaves

Saline soils are the major problem of cultivated lands of Iran. Suaeda aegyptiaca is a salt‐tolerant plant (halophytes) that grow naturally in salt‐affected areas of Iran. We have employed proteomics to identify the mechanisms of salt responsiveness in leaves of S. aegyptiaca grown under different salt concentrations. Ten‐day‐old plants were treated with 0, 150, 300, 450, and 600 mM NaCl. After 30 days of treatment, leaf samples were collected and analyzed using 2‐D‐PAGE. Out of 700 protein spots reproducible detected within replications, 102 spots showed significant response to salt treatment compared to 0 mM NaCl. We analyzed expression pattern of salt‐responsive proteins using a hierarchical and two nonhierarchical (Fuzzy ART and SOM) statistical methods and concluded that Fuzzy ART is the superior method. Forty proteins of 12 different expression groups were analyzed using LC/MS/MS. Of these, 27 protein spots were identified including proteins involved in oxidative stress tolerance, glycinebetain synthesis, cytoskeleton remodeling, photosynthesis, ATP production, protein degradation, cyanide detoxification, and chaperone activities. The expression pattern of these proteins and their possible roles in the adaptation of S. aegyptiaca to salinity is discussed.
Acute administration of inorganic nitrate reduces VO(2peak) in endurance athletes.

PURPOSE Humans can reduce inorganic nitrate (NO(3)(-)) to nitrite (NO(2)(-)), nitric oxide (NO), and other bioactive nitrogen oxides. The purpose of this study was to test the hypothesis that a single dose of inorganic nitrate before exercise might enhance the tolerance of endurance athletes to high intensity exercise. METHODS Eleven cyclists (age = 34.3 ± 4.8 yr, VO(2peak) = 65.1 ± 6.2 mL·kg(-1)·min(-1)) participated in this randomized, double-blind, crossover study. Subjects received dietary supplementation with nitrate (NaNO(3) 10 mg·kg(-1) of body mass) or a placebo (NaCl) 3 h before exercise. They then performed a cycle ergometer test that consisted of four 6-min submaximal workloads, corresponding to 2.0, 2.5, 3.0, and 3.5 W·kg(-1) of body mass, interspersed with 3 min of passive recovery. After a 5-min recovery period, subjects performed one incremental exercise test until exhaustion. RESULTS Plasma nitrate and nitrite were significantly higher (P < 0.05) 3 h after supplementation (nitrate = 250 ± 80 μM, nitrite = 2313 ± 157 nM) than after the placebo (nitrate = 29 ± 8 μM, nitrite = 1998 ± 206 nM) at resting conditions. Nitrate supplementation significantly reduced VO(2peak)(nitrate = 4.64 ± 0.35 L·min(-1), placebo = 4.82 ± 0.33 L·min(-1), P = 0.010) and the ratio between VO(2) and power at maximal intensity (nitrate = 11.2 ± 1.1 mL·min(-1)·W(-1), placebo = 11.8 ± 1.1 mL·min(-1)·W(-1), P = 0.031). This reduction of VO(2) occurred without changes in the time to exhaustion (nitrate = 416 ± 32 s, placebo = 409 ± 27 s) or in the maximal power (nitrate = 416 ± 29 W, placebo = 410 ± 28 W). CONCLUSIONS A single oral dose of inorganic nitrate acutely reduces VO(2peak)without compromising the maximal exercise performance.
Engaging the 21st-Century Student: Beyond the Lecture

ABSTRACT We are in the age of the millennial student: students are ethnically diverse, sheltered, pressured, confident, technologically advanced, team oriented, and some have helicopter parents. Furthermore, while academically inclined, these students also show increases in pressure, feeling overwhelmed, and levels of stress, in addition to academic entitlement. As our student population continues to diversify, professors should be inclined to reevaluate their teaching modalities. Today’s students need more than traditional PowerPoint lectures; they need innovation, engagement, and—to much chagrin from professors, both seasoned and new—a higher involvement with technology. This article both introduces and guides the use of five different instructional strategies that can help to supplement traditional lecture while enhancing the classroom and student in a transformative manner. These strategies will enhance the teaching profession by providing innovative techniques to higher education instructors looking to enhance and enrich their current teaching practices.