Miracle-dz/UniFAR-FTUs huggingface dataset:
A Unique Modification of the Eukaryotic Initiation Factor 5A Shows the Presence of the Complete Hypusine Pathway in Leishmania donovani

Deoxyhypusine hydroxylase (DOHH) catalyzes the final step in the post-translational synthesis of an unusual amino acid hypusine (N €-(4-amino-2-hydroxybutyl) lysine), which is present on only one cellular protein, eukaryotic initiation factor 5A (eIF5A). We present here the molecular and structural basis of the function of DOHH from the protozoan parasite, Leishmania donovani, which causes visceral leishmaniasis. The L. donovani DOHH gene is 981 bp and encodes a putative polypeptide of 326 amino acids. DOHH is a HEAT-repeat protein with eight tandem repeats of α-helical pairs. Four conserved histidine-glutamate sequences have been identified that may act as metal coordination sites. A ∼42 kDa recombinant protein with a His-tag was obtained by heterologous expression of DOHH in Escherichia coli. Purified recombinant DOHH effectively catalyzed the hydroxylation of the intermediate, eIF5A-deoxyhypusine (eIF5A-Dhp), in vitro. L. donovani DOHH (LdDOHH) showed ∼40.6% sequence identity with its human homolog. The alignment of L. donovani DOHH with the human homolog shows that there are two significant insertions in the former, corresponding to the alignment positions 159-162 (four amino acid residues) and 174-183 (ten amino acid residues) which are present in the variable loop connecting the N- and C-terminal halves of the protein, the latter being present near the substrate binding site. Deletion of the ten-amino-acid-long insertion decreased LdDOHH activity to 14% of the wild type recombinant LdDOHH. Metal chelators like ciclopirox olamine (CPX) and mimosine significantly inhibited the growth of L. donovani and DOHH activity in vitro. These inhibitors were more effective against the parasite enzyme than the human enzyme. This report, for the first time, confirms the presence of a complete hypusine pathway in a kinetoplastid unlike eubacteria and archaea. The structural differences between the L. donovani DOHH and the human homolog may be exploited for structure based design of selective inhibitors against the parasite.
Effects of Mobile Phones on Children's and Adolescents' Health: A Commentary.

The use of digital technology has grown rapidly during the last couple of decades. During use, mobile phones and cordless phones emit radiofrequency (RF) radiation. No previous generation has been exposed during childhood and adolescence to this kind of radiation. The brain is the main target organ for RF emissions from the handheld wireless phone. An evaluation of the scientific evidence on the brain tumor risk was made in May 2011 by the International Agency for Research on Cancer at World Health Organization. The scientific panel reached the conclusion that RF radiation from devices that emit nonionizing RF radiation in the frequency range 30 kHz-300 GHz is a Group 2B, that is, a "possible" human carcinogen. With respect to health implications of digital (wireless) technologies, it is of importance that neurological diseases, physiological addiction, cognition, sleep, and behavioral problems are considered in addition to cancer. Well-being needs to be carefully evaluated as an effect of changed behavior in children and adolescents through their interactions with modern digital technologies.
Bridge Individuals in Multinational Organisations

In multinational organisations, individuals who mediate or bridge between different national and cultural groups, such as headquarters (HQ) and foreign subsidiaries, play a critical role and are known as ‘bridge individuals’. This perspective article reviews the recent literature on bridge individuals and offers future research directions in which organisational psychology can contribute to the deeper understanding of the individuals in this role. I propose the interdisciplinary approach, in which knowledge of organisational psychology and other academic fields, such as cognitive linguistics, cross-cultural communication, and social network theory, are integrated when studying bridge individuals.
The Nine-Year Sustained Cost-Containment Impact of Swiss Pilot Physicians-Pharmacists Quality Circles

Background Six pioneer physicians-pharmacists quality circles (PPQCs) located in the Swiss canton of Fribourg (administratively corresponding to a state in the US) were under the responsibility of 6 trained community pharmacists moderating the prescribing process of 24 general practitioners (GPs). PPQCs are based on a multifaceted collaborative process mediated by community pharmacists for improving compliance with clinical guidelines within GPs’ prescribing practices. Objective To assess, over a 9-year period (1999–2007), the cost-containment impact of the PPQCs. Methods The key elements of PPQCs are a structured continuous quality improvement and education process; local networking; feedback of comparative and detailed data regarding costs, drug choice, and frequency of prescribed drugs; and structured independent literature review for interdisciplinary continuing education. The data are issued from the community pharmacy invoices to the health insurance companies. The study analyzed the cost-containment impact of the PPQCs in comparison with GPs working in similar conditions of care without particular collaboration with pharmacists, the percentage of generic prescriptions for specific cardiovascular drug classes, and the percentage of drug costs or units prescribed for specific cardiovascular drugs. Results For the 9-year period, there was a 42% decrease in the drug costs in the PPQC group as compared to the control group, representing a $225,000 (USD) savings per GP only in 2007. These results are explained by better compliance with clinical and pharmacovigilance guidelines, larger distribution of generic drugs, a more balanced attitude toward marketing strategies, and interdisciplinary continuing education on the rational use of drugs. Conclusions The PPQC work process has yielded sustainable results, such as significant cost savings, higher penetration of generics and reflection on patient safety, and the place of “new” drugs in therapy. The PPQCs may also constitute a solid basis for implementing more comprehensive collaborative programs, such as medication reviews, adherence-enhancing interventions, or disease management approaches.
Exclusion of alternative exon 33 of CaV1.2 calcium channels in heart is proarrhythmogenic

Significance To directly address in vivo significance of the altered CaV1.2 channel property arising from alternative splicing, we generated CaV1.2 exon 33-specific knockout (exon 33−/−) mice. Here, we showed that the exclusion of alternative exon 33 altered CaV1.2 biophysical property, leading to greater ICa density. This increase in current density induced prolongation of ventricular cardiomyocyte action potential duration, and the cardiomyocytes exhibited increased early afterdepolarizations and autonomous action potentials—hallmarks of arrhythmias. In vivo, exon 33−/− mice had increased occurrences of premature ventricular contractions, tachycardia, and lengthened QT interval. As such, exclusion of exon 33 of the CaV1.2 channel is proarrhythmogenic. Although failing human hearts had greater inclusion of exon 33, it is unclear whether the inclusion is compensatory, neutral, or damaging. Alternative splicing changes the CaV1.2 calcium channel electrophysiological property, but the in vivo significance of such altered channel function is lacking. Structure–function studies of heterologously expressed CaV1.2 channels could not recapitulate channel function in the native milieu of the cardiomyocyte. To address this gap in knowledge, we investigated the role of alternative exon 33 of the CaV1.2 calcium channel in heart function. Exclusion of exon 33 in CaV1.2 channels has been reported to shift the activation potential −10.4 mV to the hyperpolarized direction, and increased expression of CaV1.2Δ33 channels was observed in rat myocardial infarcted hearts. However, how a change in CaV1.2 channel electrophysiological property, due to alternative splicing, might affect cardiac function in vivo is unknown. To address these questions, we generated mCacna1c exon 33−/−-null mice. These mice contained CaV1.2Δ33 channels with a gain-of-function that included conduction of larger currents that reflects a shift in voltage dependence and a modest increase in single-channel open probability. This altered channel property underscored the development of ventricular arrhythmia, which is reflected in significantly more deaths of exon 33−/− mice from β-adrenergic stimulation. In vivo telemetric recordings also confirmed increased frequencies in premature ventricular contractions, tachycardia, and lengthened QT interval. Taken together, the significant decrease or absence of exon 33-containing CaV1.2 channels is potentially proarrhythmic in the heart. Of clinical relevance, human ischemic and dilated cardiomyopathy hearts showed increased inclusion of exon 33. However, the possible role that inclusion of exon 33 in CaV1.2 channels may play in the pathogenesis of human heart failure remains unclear.
Acceptance of Hepatitis B Vaccination by Pregnant Adolescents

PURPOSE:To determine (1) the rate of prenatal hepatitis B virus (HBV) vaccine acceptance in HBV nonimmune pregnant adolescents, (2) if postulated behavioral and attitudinal factors are associated with HBV vaccine, and (3) the rate of actual receipt of HBV vaccine postpartum in eligible subjects. DESIGN AND METHODS:During 1999–2000, at an inner-city tertiary-care center prenatal clinic, 160 HBV nonimmune adolescents <18 years who were receiving prenatal and delivery care at the center were identified. The research nurse provided an HBV information pamphlet and offered immediate in-hospital postpartum HBV vaccination. Risk factors for nonacceptance of the vaccine were measured with structured questionnaires and medical record review documenting care attendance. Subsequently, all subjects, irrespective of prenatal acceptance of vaccine, were offered vaccine before postpartum discharge, and the rate of actual acceptance was determined. RESULTS:In these predominantly African American (95%) adolescents, the rate of vaccine acceptance was 91%. Actual vaccination rate was 86%, but it was not associated with prior acceptance of vaccination or behavioral or attitudinal factors. CLINICAL IMPLICATIONS:Acceptance of vaccination and actual vaccination were high in this population of high-risk adolescents. The authors found that reoffering vaccine was a successful intervention, even with adolescents who had less-than-optimal attendance at prenatal visits. Given the high rate of acceptance and vaccination in this setting, the authors would encourage public health programs to implement vaccination programs in adolescent prenatal clinics and to offer vaccination postpartum to those who do not receive it prenatally.
Update on integrated biomarkers for assessment of long-term risk of cardiovascular complications in initially healthy subjects and patients with manifest atherosclerosis

Risk stratification for cardiovascular diseases (CVD) remains suboptimal even after the introduction of global risk assessment by various scores. This has prompted the search for additional biomarkers which might help to improve risk stratification. Basically, there are blood biomarkers representing various pathophysiological pathways of atherosclerosis, and markers of subclinical disease. Since inflammatory processes accompany all stages of atherosclerosis, measurement of plasma/serum concentrations of circulating inflammatory biomarkers have received great attention. Such biomarkers can be measured systemically by sensitive assays, and elevated concentrations in the circulation have been shown to be associated with future CVD events. Thus, they might add to the predictive value of the atherogenic lipoprotein phenotype to further improve CVD risk assessment. In addition, several non-invasive imaging techniques are available for which also a predictive value for CVD could be established. However, for most of these biomarkers the clinical utility has not yet been firmly established. This review attempts to give an update on the potential use of biomarkers for risk stratification in initially healthy subjects and patients with manifest, chronic atherosclerosis, particularly focusing on the integrated value of the combination of these markers.
Sampling-based tasks scheduling in dynamic grid environment

In this paper, we propose a new solution for data mining task scheduling in Grid environment. First, we propose a sample-based application run time evaluation. Then, we propose a cost model for predicting the data transfer time on Grid. Finally, according the priori estimation of the application response time and the data transfer time, we propose the method for tasks scheduling in grid environment.
Decentralized secure framework for social collaborative Internet of Things

The Social-Collaborative Internet of Things (SCIoT) provides the ability for objects to autonomously establish social relationship among them based on the rules imposed by its owners'. This paper proposes a new secure framework for SCIoTto tackle the issues related to security and privacy. The proposed framework adopts a decentralized architecture to handle the problems of large-scale deployment and management of heterogeneous objects in different Internet of Things platforms. The proposed framework consists Relationship Based Dynamic Trust Management Protocol to ensure trustworthiness among objects in the dynamic environment of SCIoT.
Large bolus dose vs. continuous infusion of cisatracurium during hypothermic cardiopulmonary bypass surgery

Background and objective: We investigated whether a high bolus dose of cisatracurium (8× ED95) given at induction can provide muscle relaxation for the major part of a cardiac procedure with hypothermic cardiopulmonary bypass, avoid important postoperative residual curarization and cause no waste of product. Methods: Twenty patients were randomly assigned either to Group 1 (n = 10) or Group 2 (n = 10). Those in Group 1 were given cisatracurium in a high bolus dose (0.4 mg kg−1). Those in Group 2 received cisatracurium 0.1mg kg−1 at induction followed after 30 min by a continuous infusion of cisatracurium. As an escape medication in case of patient movement, a bolus dose of cisatracurium 0.03 mg kg−1 was given. Results: In Group 1 (large cisatracurium bolus dose), the clinical duration of effect (until T1/T0 = 25%) was 110 min. Six of 10 patients in Group 1 required additional boluses of cisatracurium intraoperatively. Four of these six had received an additional bolus near the end of surgery and had a train‐of‐four (TOF) ratio = 0 at the end. The other four patients in Group 1 had a final TOF ratio >0.9. In Group 2 (continuous cisatracurium infusion), only two patients had a TOF ratio >0.9 at the end of surgery, no patient moved and none received additional boluses. The total amount of cisatracurium used in the bolus and infusion Groups was 34.5 ± 7.8 and 21.3 ± 5.7 mg, respectively (P = 0.0004). Conclusions: For continued neuromuscular block during hypothermic cardiac surgery, a high bolus dose of cisatracurium appears to be safe, although it is not an alternative to a continuous infusion, as its neuromuscular blockade does not cover the intraoperative period and a high incidence of movements occurs. In the patients who received a high bolus dose of cisatracurium, postoperative residual curarization appeared after additional boluses had been given. The consumption of cisatracurium by high bolus was significantly greater than with continuous infusion.
Interventions to improve antiretroviral therapy adherence among adolescents in low- and middle-income countries: A systematic review of the literature

Introduction Globally, an estimated 30% of new HIV infections occur among adolescents (15–24 years), most of whom reside in sub-Saharan Africa. Moreover, HIV-related mortality increased by 50% between 2005 and 2012 for adolescents 10–19 years while it decreased by 30% for all other age groups. Efforts to achieve and maintain optimal adherence to antiretroviral therapy are essential to ensuring viral suppression, good long-term health outcomes, and survival for young people. Evidence-based strategies to improve adherence among adolescents living with HIV are therefore a critical part of the response to the epidemic. Methods We conducted a systematic review of the peer-reviewed and grey literature published between 2010 and 2015 to identify interventions designed to improve antiretroviral adherence among adults and adolescents in low- and middle-income countries. We systematically searched PubMed, Web of Science, Popline, the AIDSFree Resource Library, and the USAID Development Experience Clearinghouse to identify relevant publications and used the NIH NHLBI Quality Assessment Tools to assess the quality and risk of bias of each study. Results and discussion We identified 52 peer-reviewed journal articles describing 51 distinct interventions out of a total of 13,429 potentially relevant publications. Forty-three interventions were conducted among adults, six included adults and adolescents, and two were conducted among adolescents only. All studies were conducted in low- and middle-income countries, most of these (n = 32) in sub-Saharan Africa. Individual or group adherence counseling (n = 12), mobile health (mHealth) interventions (n = 13), and community- and home-based care (n = 12) were the most common types of interventions reported. Methodological challenges plagued many studies, limiting the strength of the available evidence. However, task shifting, community-based adherence support, mHealth platforms, and group adherence counseling emerged as strategies used in adult populations that show promise for adaptation and testing among adolescents. Conclusions Despite the sizeable body of evidence for adults, few studies were high quality and no single intervention strategy stood out as definitively warranting adaptation for adolescents. Among adolescents, current evidence is both sparse and lacking in its quality. These findings highlight a pressing need to develop and test targeted intervention strategies to improve adherence among this high-priority population.
A general method for the derivation of the functional forms of the effective energy terms in coarse-grained energy functions of polymers. II. Backbone-local potentials of coarse-grained O1→4-bonded polyglucose chains.

Based on the theory of the construction of coarse-grained force fields for polymer chains described in our recent work [A. K. Sieradzan et al., J. Chem. Phys. 146, 124106 (2017)], in this work effective coarse-grained potentials, to be used in the SUGRES-1P model of polysaccharides that is being developed in our laboratory, have been determined for the O⋯O⋯O virtual-bond angles (θ) and for the dihedral angles for rotation about the O⋯O virtual bonds (γ) of 1 → 4-linked glucosyl polysaccharides, for all possible combinations of [α,β]-[d,l]-glucose. The potentials of mean force corresponding to the virtual-bond angles and the virtual-bond dihedral angles were calculated from the free-energy surfaces of [α,β]-[d,l]-glucose pairs, determined by umbrella-sampling molecular-dynamics simulations with the AMBER12 force field, or combinations of the surfaces of two pairs sharing the overlapping residue, respectively, by integrating the respective Boltzmann factor over the dihedral angles λ for the rotation of the sugar units about the O⋯O virtual bonds. Analytical expressions were subsequently fitted to the potentials of mean force. The virtual-bond-torsional potentials depend on both virtual-bond-dihedral angles and virtual-bond angles. The virtual-bond-angle potentials contain a single minimum at about θ=140° for all pairs except β-d-[α,β]-l-glucose, where the global minimum is shifted to θ=150° and a secondary minimum appears at θ=90°. The torsional potentials favor small negative γ angles for the α-d-glucose and extended negative angles γ for the β-d-glucose chains, as observed in the experimental structures of starch and cellulose, respectively. It was also demonstrated that the approximate expression derived based on Kubo's cluster-cumulant theory, whose coefficients depend on the identity of the disugar units comprising a trisugar unit that defines a torsional potential, fits simultaneously all torsional potentials very well, thus reducing the number of parameters significantly.
Neural networks. II. What are they and why is everybody so interested in them now?

For part I, see ibid., vol. EX-2, no. 4, p. 10-11 (1987). The learning ability of neural networks and their ability to generalize and to abstract or generate ideals from an imperfect training set are examined. Their potential for multiprocessing is considered. A brief history of neural network research is followed by a discussion of their architectures and a presentation of several specific architectures and learning techniques. The Cauchy machine, which represents a possible solution to the local minima problem encountered with virtually every other neural network training algorithm, is described. The outlook for neural nets is briefly considered. <<ETX>>
Determination of the initial DNA damage and residual DNA damage remaining after 12 hours of repair in eleven cell lines at low doses of irradiation.

PURPOSE To determine the relationship between DNA damage and radiosensitivity at low doses (1-10 Gy) for the initial DNA damage and residual DNA damage remaining after 12-h repair. MATERIALS AND METHODS Eleven cell lines, normal human lung epithelial L132, HT29 human colon carcinoma, ATs4 human ataxia telangiectasia, normal CHO-K1 hamster, repair-deficient xrs1 and xrs5 mutants, repair-deficient SCID rodent cell line, the human normal fibroblast 1BR.3, human ataxia telangiectasia fibroblast AT1BR and the repair-deficient fibroblasts 180BR.B and 46BR.1 were irradiated with 60Co gamma-rays. Radiosensitivity was measured by clonogenic survival assay. DNA damage was measured by fluorometric analysis of DNA unwinding (FADU). RESULTS The radiosensitivity in the 11 cell lines ranged from SF2 of 0.02-0.61. By FADU assay, the undamaged DNA at 5-Gy ranged from 56 to 93%. The initial DNA damage and radiosensitivity were highly correlated (r2 = 0.81). After 5-Gy irradiation and 12-h repair, two groups of cell lines emerged. Group 1 restored undamaged DNA to a level ranging from 94 to 98%. Group 2 restored the undamaged DNA to a level ranging from 77 to 82%. No correlation was seen between residual DNA damage remaining after 12-h repair and radiosensitivity. CONCLUSION It is shown that the initial DNA damage correlates with radiosensitivity at low doses of irradiation. This suggests that the initial DNA damage must be considered as a determinant for radiosensitivity.
Desirable Portfolios in Fixed Income Markets: Application to Credit Risk Premiums

An arbitrage portfolio provides a cash flow that can never be negative at zero cost. We define the weaker concept of a “desirable portfolio” delivering cash flows with negative risk at zero cost. Although these are not completely risk-free investments and subject to the risk measure used, they can provide attractive investment opportunities for investors. We investigate in detail the theoretical aspects of this portfolio selection procedure and the existence of such opportunities in fixed income markets. Then, we present two applications of the theory: one in analyzing market integration problem and the other in gauging the credit quality of defaultable bonds in a portfolio. We also discuss the model calibration and provide some numerical illustrations.