Miracle-dz/UniFAR-FTUs huggingface dataset:
More potent inhibition of human CYP2A6 than mouse CYP2A5 enzyme activities by derivatives of phenylethylamine and benzaldehyde

1. A rapid 96-well plate assay method was developed and validated to measure liver microsomal coumarin 7-hydroxylation in vitro. 2. The method was used to test inhibition of human and mouse CYP2A enzymes by three phenylethylamine derivatives 2- (p -tolyl)-ethylamine, amphetamine, 2-phenylethylamine and benzaldehyde, and two of its derivatives, 4-methylbenzaldehyde and 4-methoxybenzaldehyde. 3. The benzaldehyde derivatives were more potent inhibitors of CYP2A5 than the phenylethylamines. The K ic value of 4-methylbenzaldehyde was 3.4 µ M and for 4-methoxybenzaldehyde it was 0.86 µ M for CYP2A5. 4. Amphetamine is a weak inhibitor of CYP2A6, whereas benzaldehyde is a suicide inhibitor with K inact = 0.16 min − 1 and K I = 18 µ M. The K ic values of 2-phenylethylamine, 2- (p -tolyl)-ethylamine, 4-methylbenzaldehyde and 4-methoxybenzaldehyde were 1.13, 0.23, 0.36 and 0.73 µ M for CYP2A6, respectively. 5. Novel potent inhibitors were found for CYP2A6 and, except for 4-methoxybenzaldehyde, all the compounds inhibited CYP2A5 and CYP2A6 enzymes differentially. These data add to the refinement of CYP2A enzyme active sites and provide chemical leads for developing novel chemical inhibitors of the CYP2A6 enzyme.
Evidence for improved muscle activation patterns after retraining of reaching movements with the MIME robotic system in subjects with post-stroke hemiparesis

Previously, we reported that chronic stroke subjects had significant improvements in isometric strength, free reaching extent, and clinical evaluations of function after training in the mirror-image movement enabler (MIME) robotic device. Our primary goal in this analysis was to investigate the hypothesis that the robotic training promoted improved muscle activation patterns. To this end, we examined the interaction forces, kinematics, and electromyograms recorded during training of eight different movement patterns in active-constrained mode. In this mode, the robot constrained the reaching movements to be toward the target, and the movement velocity was proportional to the force produced along the trajectory. Thirteen chronic stroke subjects trained in MIME for 24 1-h sessions over an eight-week period. Work output was significantly increased by week five in all eight movement patterns. Low-level subjects increased their extent of reach, while high-level subjects increased their speed. Directional errors in force production were reduced in six of eight movement patterns. Electromyographic data provided evidence for improved muscle activation patterns in the four movement patterns that started at tabletop level and ended at shoulder level. In contrast, there was no evidence of improved muscle activation patterns in any of the tabletop movements, with increased activation of antagonists in two movement patterns. This dichotomy may have been related to compensation at the shoulder girdle during movements that remained at tabletop level. A simple biomechanical model will be introduced to demonstrate the likelihood of this possibility.
Association Analysis of the GSK-3β T–50C Gene Polymorphism with Schizophrenia and Bipolar Disorder

Glycogen synthase kinase-3β (GSK-3β) has been implicated in the pathogenesis of major psychoses. In this paper, the T–50C polymorphism of the GSK-3β gene has been studied in patients with schizophrenia (n = 432), patients with bipolar disorder (n = 416) and in a healthy control group (n = 408). Consensus diagnosis by at least two psychiatrists was made for each patient, according to DSM-IV and ICD-10 criteria, using the Structured Clinical Interview for DSM-IV Axis I Disorders. Genotypes were established by the polymerase chain reaction-restriction fragment length polymorphism method. We have found a trend towards an association for the C allele in the whole group of schizophrenic patients (p = 0.088) and for the heterozygous T/C genotype of bipolar patients (0.095). Significant differences of genotype distribution and allele frequencies of the T–50C polymorphism were found in the female group of bipolar II patients (p = 0.015 for genotypes and p = 0.009 for alleles). In conclusion, this polymorphism may be associated with female gender in bipolar II disorder.
Interleukin-1 and Endothelin Stimulate Distinct Species of Diglycerides That Differentially Regulate Protein Kinase C in Mesangial Cells (*)

Diglycerides are phospholipid-derived second messengers that serve as cofactors for protein kinase C activation. We have previously shown that, in rat glomerular mesangial cells, the cytokine, interleukin-1α, and the vasoactive peptide, endothelin, generate diglycerides from unique phospholipid precursors. However, neither the molecular species of these diglycerides nor their biological actions were determined. It is now hypothesized that interleukin-1- and endothelin-treated mesangial cells form distinct molecular species of diglycerides which may serve different roles as intracellular signaling molecules. Diglyceride molecular species were resolved and quantified by TLC and high performance liquid chromatography as diglyceride-[C]acetate derivatives. Endothelin stimulates predominantly ester-linked species (diacylglycerols) in contrast to interleukin-1 which stimulates only ether-linked species (alkyl,acyl- and alkenyl,acylglycerols). In support of these data, interleukin-1-treated mesangial cells hydrolyze ethanolamine plasmalogens, vinyl ether-linked phospholipids. It has been reported that ether-linked, in contrast to ester-linked, diglyceride species do not activate protein kinase C activity. Thus, we next assessed membrane protein kinase C activity in endothelin- or interleukin-1-treated mesangial cells. Even though interleukin-1 has no effect upon basal protein kinase C activity, this cytokine, through the formation of ether-linked diglyceride second messengers, inhibits endothelin, platelet-activating factor, or arginine vasopressin-stimulated protein kinase C activity. We further demonstrate that ester-linked diacylglycerols but not alkyl,acyl- or alkenyl,acylglycerols substitute for phorbol esters in a cell-free protein kinase C assay. In addition, alkenyl,acylglycerols inhibit diacylglycerol-stimulated immunoprecipitated protein kinase C α activity in vitro and total protein kinase C activity in permeabilized mesangial cells ex vivo. Taken together, these data suggest that interleukin-1-induced formation of ether-linked diglycerides may physiologically serve to down-regulate receptor-mediated protein kinase C activity and that individual molecular species of diglycerides may serve different roles as intracellular signaling molecules.
The Cold War as comparative political thought

Abstract The aim of this article is to provide a programmatic statement for a research agenda in the comparative political thought of the Cold War. As an innovative methodology for the study of political ideas, the author contends that comparative political theory connects up very well with the ways in which Cold War historians have come to frame their questions: systematically applying its principles therefore offers an interesting opportunity to take the recent scholarship forward. The first section reviews the treatment of ideas across phases of the Cold War historiography, and proposes that an approach styled on comparative political theory potentially brings out two general qualities of Cold War ideas, which are often missed: what the author calls their granularity and embeddedness. At the same time some prospects are raised for reconciling the political and cultural histories of the Cold War. The second section focuses on the aspect of comparison, and situates the research programme in the context of the recent trend towards the study of international history. The third section is the most constructive. An indicative series of projects is offered which such a programme might pursue. The concept of the Cold War ‘thought-practice’ is proposed as the most promising unit of analysis by which the figure of the political theorist might contribute to the interpretation of Cold War history.
Fibroblast Growth Factor Homologous Factors

Fibroblast growth factor homologous factors (FHFs) are a noncanonical subset of intracellular fibroblast growth factors that have been implicated in a variety of neurobiological processes and in disease. They are most prominently regulators of voltage-gated Na+ channels (NaVs). In this review, we discuss new insights into how FHFs modulate NaVs. This is followed by a summary of a growing body of evidence that FHFs operate in much broader fashion. Finally, we highlight unknown aspects of FHF function as areas of future interest.
Postexercise protein intake enhances whole-body and leg protein accretion in humans.

PURPOSE Exercise increases the use of amino acids for glucose production and stimulates the oxidation of amino acids and other substrates to provide ATP for muscular contraction, and thus the availability of amino acids and energy for postexercise muscle protein synthesis may be limiting. The purpose of this study was to determine the potential of postexercise nutrient intake to enhance the recovery of whole-body and skeletal muscle protein homeostasis in humans. METHODS Primed-continuous infusions of L-[1-13C]leucine and L-[ring-2H5]phenylalanine were initiated in the antecubital vein and blood was sampled from a femoral vein and a heated (arterialized) hand vein. Each study consisted of a 30-min basal, a 60-min exercise (bicycle at 60% VO2max), and a 180-min recovery period. Five men and five women were studied three times with an oral supplement administered immediately following exercise in random order: NO = 0, 0, 0; SUPP = 0, 8, 3; or SUPP+PRO = 10, 8, 3 g of protein, carbohydrate, and lipid, respectively. RESULTS Compared to NO, SUPP did not alter leg or whole-body protein homeostasis during the recovery period. In contrast, SUPP+PRO increased plasma essential amino acids 33%, leg fractional extraction of phenylalanine 4-fold, leg uptake of glucose 3.5-fold, and leg and whole-body protein synthesis 6-fold and 15%, respectively. Whereas postexercise intake of either NO or SUPP resulted in a net leg release of essential amino acids and net loss of whole-body and leg protein, SUPP+PRO resulted in a net leg uptake of essential amino acids and net whole-body and leg protein gain. CONCLUSIONS These findings suggest that the availability of amino acids is more important than the availability of energy for postexercise repair and synthesis of muscle proteins.
DOES HEALTH MATTER? EVIDENCE FROM THE EU15 AND TURKEY

This study provides evidence on the role of health in accounting for income in sixteen countries (EU15 and Turkey). The relationship between health and income was analyzed with dynamic panel regression by using panel data for the 1970-2013 periods. The empirical evidence suggests that two health measures, life expectancy at birth and mortality rate have positive impacts on income. The estimates show that the relationship is even stronger for EU15 countries compared with Turkey. http://dx.doi. org/10.17130/ijmeb.2018445663
Effect of transforming growth factor beta1 on chondrogenic differentiation of cultured equine mesenchymal stem cells.

OBJECTIVE To determine the morphologic and phenotypic effects of transforming growth factor beta1 (TGFbeta1) on cultured equine mesenchymal stem cells (MSC) and articular chondrocytes. SAMPLE POPULATION Bone marrow aspirates and articular cartilage samples from a 2-year-old and two 8-month-old horses. PROCEDURE After initial isolation and culture, MSC and chondrocytes were cultured in Ham's F-12 medium supplemented with TGF-beta1 at a concentration of 0, 1, 5, or 10 ng/ml. Medium was exchanged on day 2, and cells were harvested on day 4. Medium was assayed for proteoglycan (PG) content. Total RNA was isolated from cell cultures, and expression of aggrecan, decrin, collagen type-I, and collagen type-II mRNA was assessed by means of Northern blot analyses. Cell cultures were stained with H&E or toluidine blue and examined histologically. Additional cultures were examined after immunohistochemical staining for type-I and -II collagen. RESULTS MSC cultures exposed to TGF-beta1 had an increased cellular density with cell layering and nodule formation that was most pronounced in cultures treated with 5 ng of TGF-beta1/ml. Expression of collagen type-II mRNA in MSC cultures exposed to 5 ng of TGF-beta1/ml was 1.7 times expression in control cultures, and expression of collagen type-I mRNA was 2.8 times expression in control cultures. Treatment of MSC with TGF-beta1 led to dose-related increases in area and intensity of type-II collagen immunoreaction. CONCLUSION Results suggest that TGF-beta1 enhances chondrogenic differentiation of bone marrow-derived MSC in a dose-dependent manner.
Risk Taking to Succeed: Occupational Choice and the Positive Effects of Progressive Taxation

Occupations differ in their degree of earnings uncertainty. Progressive taxation provides insurance to risk-averse workers against adverse earnings outcomes. As a result, progressive tax systems distort the price of risk and influence the mo- bility and sorting of workers across occupations. This paper proposes a theory to understand the effect of the degree of tax progressivity on workers’ career choices when markets are incomplete. We quantify the distortion and we find that tax progressivity incentives young workers to take on risk, thus partially completing the insurance markets. Hence, we provide a new perspective on the welfare cost of uninsurable earnings risk. To that end, we employ micro-data on occupational mobility and earnings from the United States and Germany to estimate a model of occupational choice and uninsurable earnings uncertainty. The model predicts that, as observed in the data, everything else equal, were US workers to face the relatively more progressive earnings tax function of Germany, a larger fraction of young workers will take risk and they will end up working into safer occupations.
Optimization of surge arrester's location

The lightning surges being considered the most dangerous events in power distribution systems, knowledge of the same allows to obtain a better selection and coordination of protection devices. Moreover, a better knowledge of lightning surges permits to optimize the location of device protection, to reduce the insulation costs of the installations, and to operate with risks of failure that are well known. The development of a computer application allowing determination of the optimal position of the surge arrester in power systems minimizes the risk of failure, thus permitting the selection of appropriate protection schemes for each network. As a consequence, protection costs are being reduced in accordance with the costs of the elements actually protected and the continuity of service to be achieved.
Introduction of a New Mobile Player App Store in Selected Countries of Southeast Asia

Trends in modern society have a significant impact on the way organizations operate. The use of mobile phones makes it possible to create completely new high-availability communication and business channels. Mobile phones are used in mobile marketing, which has come to the fore via SMS marketing. In this article, the focus is on the use of mobile phones in e-business. The introduction of a new mobile player app store was analyzed through research conducted in 2017. The aim of the research was to find out whether it is possible—in terms of the sustainability of the consumption of a marketing product—to introduce a single campaign with the same content but in different language mutations in selected markets, or whether it is necessary to use a completely different campaign and means of communication for each market. Overall, 287 respondents from the Philippines, Thailand, and India were examined. The dependency between the socio-demographic characteristics of the respondents (country, gender, and age) and site engagement was tested, and user experience was tested, too. The results of the research revealed that there was no dependency between belonging to the selected countries and site engagement. Furthermore, there was also no dependency between gender and site engagement. On the other hand, there was a statistically significant dependency between belonging to the country and the design of the website.
Improving citizen engagement : community conversations and collaboration on ABC local radio

Public broadcasting radio now operates at a time of political disengagement, media consolidation and digital fragmentation. The basis of this thesis is that new empirical research is essential to assess the significance of these latest developments that shape public broadcasting and to explore the possibilities for radio broadcasters to expand engagement with their audiences. Through an industry-informed and focused inquiry into local radio, this thesis advances an understanding of journalism ‘as conversation’, specifically those professional practices that attend to improving the diversity and depth of discourse and civic engagement. The research data collection methods for the investigation include: observation and discourse analysis of a series of radio forums covering contentious local issues in Tasmania and long qualitative interviews with journalists, participants- and leaders of public broadcasting. It finds that an active commitment to collaboration, voice and diversity in conversational radio journalism practice can facilitate citizen engagement and public trust, as long as sufficient time and resources support such activity. Creating a space for intense focus on local issues, with debate framed transparently, not only produces opportunities for citizens to participate more fully in their communities, but creates empathy and builds consensus. This suggests that a wider function for local journalism is to not only inform the public, but also to pursue collaborative practices which empower citizens and foster social inclusion. As such, the thesis contributes to scholarship about the changing values of news and journalism, public broadcasting, journalism-as-conversation, and radio, and contributes insight to inform contemporary practice.
Process simulation for software engineering education

Training and learning are one important purpose of Software Process Simulation (SPS). Some previous reviews showed a noticeable number of studies that combine SPS and Soft- ware Engineering Education (SEE). The objective of this research is to present the latest state-of-the-art of this area, and more importantly provide practical support for the effective adoption of SPS in educational context. We conducted an extended Systematic Literature Review (SLR) based on our previous reviews. The review identified 42 primary studies from 1992 to 2013. This paper presents the preliminary results by answering the research questions. The overall findings confirmed the positive impact of SPS on education. The detailed discussions and recommendations may offer reference value to the community.
Plectin repeats and modules: strategic cysteines and their presumed impact on cytolinker functions

Plectin, a member of the cytolinkers protein family, plays a crucial role in cells as a stabilizing element of cells against mechanical stress. Its absence results in muscular dystrophy, skin blistering, and signs of neuropathy. The C‐terminal domain of plectin contains several highly homologous repeat domains that also occur in other cytolinkers. Secondary structure analysis revealed that the building block of these domains, the PLEC repeat, is similar to the ankyrin repeat. We present a model that attempts to explain how the C‐terminal domain, which comprises ∼1900 amino acid, could be stabilized to maintain its structural integrity even under extensive mechanical stress. In this model, larger solenoid modules formed from PLEC repeats can be disulfide‐bridged via conserved cysteines. Our hypothesis suggests that this process could be mediated by cytoplasmic NOS‐generated products, such as the radical peroxynitrite. Reinforcement of molecular structure would provide a rationale why during exercising or physical stress radicals areformed without necessarily being deleterious. This article contains supplementary material that may be viewed at the BioEssays website at http://www.interscience. wiley.com/jpages/0265‐9247/suppmat/23/v23_11. 1064.html. BioEssays 23:1064–1069, 2001. © 2001 John Wiley & Sons, Inc.
Insulin Stimulates Amino Acid and Lipid Metabolism in Isolated Fetal Rat Hepatocytes

ABSTRACT. Although fetal hyperinsulinemia is associated with excessive deposition of glycogen in liver, both in vivo and in vitro studies show little effect of insulin on glycogen synthesis from glucose or the activity of the enzyme glycogen synthase in the fetus. To investigate whether lack of insulin effect extends to other fetal metabolic processes, we compared the influence of insulin on amino acid uptake (14C-α-aminoisobutyric acid) and lipid synthesis [14C-acetate) in freshly isolated hepatocytes from 21-day fetal (F) and adult (A) rats. Viability of F and A hepatocytes was documented by trypan blue exclusion (>90%). In A, insulin stimulated 14C-α-aminoisobutyric acid uptake in a dose dependent manner with an apparent Km at 2 ng/ml and a Vmax at 10 ng/ml. When corrected for cell surface area, F cells responded to insulin in a similar dose response manner, although absolute values per 1 x 106 cells always remained lower. In contrast, whereas A cells demonstrated a typical dose dependent response of 14C-acetate incorporation into lipid with a Km at 5 ng/ml and Vmax at 10 ng/ml of insulin, F cells remained totally unresponsive when the concentration of acetate was 5 mM or less. However, at higher medium acetate concentrations (15–30 mM) fetal responses were equal to or greater than that of adult, both basally and with insulin. These findings suggest differences in the maturation of insulin-mediated processes in fetal rat hepatocytes; effects on amino acid uptake appear earlier than those on lipid or glycogen synthesis.
The methylproteome and the intracellular methylation network

Since its discovery more than 50 years ago, post‐translational modification (PTM) of proteins via methylation has grown in prominence, its involvement having been recognised in a number of central processes in the cell. Of these, the best characterised is its role in the epigenetic code. However, there is increasing evidence that its role extends far beyond this and we propose that it is a key regulator in interactome dynamics. In this review, we focus on the role of methylation in regulating protein‐protein interactions and illustrate, by providing a broad‐scale summary of our current knowledge of methylation and its impact on systems biology, how this can ultimately affect interactome dynamics. We describe the variety of analytical techniques available for the study of the methylproteome, comment on their advantages and limitations, and consider how these tools can help elucidate how methylation regulates the dynamics of the interactome. The insights gained from methyltransferase‐substrate networks will be summarised and the ability of protein methylation to facilitate or block protein‐protein interactions as well as their interplay with other post‐translational modifications, in particular phosphorylation, is highlighted. Finally, the importance of methylation in pathology‐associated protein interaction networks will be discussed using examples involving human diseases and the p53 protein.