LLukas22/scidocs huggingface dataset:
Three-dimensional cluster analysis identifies interfaces and functional residue clusters in proteins.

Three-dimensional cluster analysis offers a method for the prediction of functional residue clusters in proteins. This method requires a representative structure and a multiple sequence alignment as input data. Individual residues are represented in terms of regional alignments that reflect both their structural environment and their evolutionary variation, as defined by the alignment of homologous sequences. From the overall (global) and the residue-specific (regional) alignments, we calculate the global and regional similarity matrices, containing scores for all pairwise sequence comparisons in the respective alignments. Comparing the matrices yields two scores for each residue. The regional conservation score (C(R)(x)) defines the conservation of each residue x and its neighbors in 3D space relative to the protein as a whole. The similarity deviation score (S(x)) detects residue clusters with sequence similarities that deviate from the similarities suggested by the full-length sequences. We evaluated 3D cluster analysis on a set of 35 families of proteins with available cocrystal structures, showing small ligand interfaces, nucleic acid interfaces and two types of protein-protein interfaces (transient and stable). We present two examples in detail: fructose-1,6-bisphosphate aldolase and the mitogen-activated protein kinase ERK2. We found that the regional conservation score (C(R)(x)) identifies functional residue clusters better than a scoring scheme that does not take 3D information into account. C(R)(x) is particularly useful for the prediction of poorly conserved, transient protein-protein interfaces. Many of the proteins studied contained residue clusters with elevated similarity deviation scores. These residue clusters correlate with specificity-conferring regions: 3D cluster analysis therefore represents an easily applied method for the prediction of functionally relevant spatial clusters of residues in proteins.
‘Public service motivation’ as an argument for government provision

A public service motivation (PSM) inclines employees to provide effort out of concern for the impact of that effort on a valued social service. Though deemed to be important in the literature on public administration, this motivation has not been formally considered by economists. When a PSM exists, this paper establishes conditions under which government bureaucracy can better obtain PSM motivated effort from employees than a standard profit maximizing firm. The model also provides an efficiency rationale for low-powered incentives in both bureaucracies and other organizations producing social services.  2000 Elsevier Science S.A. All rights reserved.
Multiple Fault Diagnosis Method in Multistation Assembly Processes Using Orthogonal Diagonalization Analysis

Dimensional control has a significant impact on overall product quality and performance of large and complex multistation assembly systems. To date, the identification of processrelated faults that cause large variations of key product characteristics (KPCs) remains one of the most critical research topics in dimensional control. This paper proposes a new approach for multiple fault diagnosis in a multistation assembly process by integrating multivariate statistical analysis with engineering models. The proposed method is based on the following steps: (i) modeling of fault patterns obtained using state space representation of process and product information that explicitly represents the relationship between process-related error sources denoted by key control characteristics (KCCs) and KPCs, and (ii) orthogonal diagonalization of measurement data using principal component analysis (PCA) to project measurement data onto the axes of an affine space formed by the predetermined fault patterns. Orthogonal diagonalization allows estimating the statistical significance of the root cause of the identified fault. A case study of fault diagnosis for a multistation assembly process illustrates and validates the proposed methodology. DOI: 10.1115/1.2783228
Making Sense of the Comparative Advantage Gains from Trade: Comment on Batra

This paper addresses Ravi Batra's (2002 ) criticism of the basic comparative advantage gains-from-trade model. While Batra's criticism is based on the selection view interpretation of real income, the gains from trade can only be properly understood from the options view interpretation of real income. I also show how a recent empirical implementation of the gains-from-trade model defies Batra's claim that "the consumption gain . . . is not subject to measurement" (2002, p. 642). Copyright © 2006 The Author; Journal compilation © 2006 Blackwell Publishing Ltd.
Ethanol-stimulated behaviour in mice is modulated by brain catalase activity and H2O2 rate of production

Abstract Rationale. Over the last few years, a role for the brain catalase-H2O2 enzymatic system has been suggested in the behavioural effects observed in rodents after ethanol administration. This role seems to be related to the ability of cerebral catalase to metabolise ethanol to acetaldehyde using H2O2 as a co-substrate. On the other hand, it has been shown that normobaric hyperoxia increases the rate of cerebral H2O2 production in rodents in vivo. Thus, substrate-level changes could regulate brain catalase activity, thereby modulating the behavioural effects of ethanol. Objectives. The aim of the present study was to assess if the enhancement of cerebral H2O2 production after hyperoxia exposure results in a boost of ethanol-induced locomotion in mice. Methods. CD-1 mice were exposed to air or 99.5% O2 inhalation (for 15, 30, or 45 min) and 0, 30, 60 or 120 min after this treatment, ethanol-induced locomotion was measured. The H2O2-mediated inactivation of endogenous brain catalase activity following an injection of 3-amino-1,2,4-triazole was used as a measure of the rate of cerebral H2O2 production. Results. Hyperoxia exposure (30 or 45 min) potentiated the locomotor-stimulating effects of ethanol (2.5 or 3.0 g/kg), whereas cocaine (4 mg/kg) or caffeine (15 mg/kg)-induced locomotion and blood ethanol levels were unaffected. Moreover, the results also confirmed brain H2O2 overproduction in mice. Conclusions. The present results suggest that an increase in brain H2O2 production potentiates ethanol-induced locomotion. Therefore, this study provides further support for the notion that the brain catalase-H2O2 system, and by implication centrally formed acetaldehyde, plays a key role in the mediation of ethanol's psychopharmacological effects.
Validity and reliability of a novel immunosuppressive adverse effects scoring system in renal transplant recipients

BACKGROUND
After renal transplantation, many patients experience adverse effects from maintenance immunosuppressive drugs. When these adverse effects occur, patient adherence with immunosuppression may be reduced and impact allograft survival. If these adverse effects could be prospectively monitored in an objective manner and possibly prevented, adherence to immunosuppressive regimens could be optimized and allograft survival improved. Prospective, standardized clinical approaches to assess immunosuppressive adverse effects by health care providers are limited. Therefore, we developed and evaluated the application, reliability and validity of a novel adverse effects scoring system in renal transplant recipients receiving calcineurin inhibitor (cyclosporine or tacrolimus) and mycophenolic acid based immunosuppressive therapy.


METHODS
The scoring system included 18 non-renal adverse effects organized into gastrointestinal, central nervous system and aesthetic domains developed by a multidisciplinary physician group. Nephrologists employed this standardized adverse effect evaluation in stable renal transplant patients using physical exam, review of systems, recent laboratory results, and medication adherence assessment during a clinic visit. Stable renal transplant recipients in two clinical studies were evaluated and received immunosuppressive regimens comprised of either cyclosporine or tacrolimus with mycophenolic acid. Face, content, and construct validity were assessed to document these adverse effect evaluations. Inter-rater reliability was determined using the Kappa statistic and intra-class correlation.


RESULTS
A total of 58 renal transplant recipients were assessed using the adverse effects scoring system confirming face validity. Nephrologists (subject matter experts) rated the 18 adverse effects as: 3.1 ± 0.75 out of 4 (maximum) regarding clinical importance to verify content validity. The adverse effects scoring system distinguished 1.75-fold increased gastrointestinal adverse effects (p=0.008) in renal transplant recipients receiving tacrolimus and mycophenolic acid compared to the cyclosporine regimen. This finding demonstrated construct validity. Intra-class correlation was 0.81 (95% confidence interval: 0.65-0.90) and Kappa statistic of 0.68 ± 0.25 for all 18 adverse effects and verified substantial inter-rater reliability.


CONCLUSIONS
This immunosuppressive adverse effects scoring system in stable renal transplant recipients was evaluated and substantiated face, content and construct validity with inter-rater reliability. The scoring system may facilitate prospective, standardized clinical monitoring of immunosuppressive adverse drug effects in stable renal transplant recipients and improve medication adherence.
(Re)-conceptualizing design approaches for mobile language learning

An exploratory study conducted at George Brown College in Toronto, Canada between 2007 and 2009 investigated language learning with mobile devices as an approach to augmenting ESP learning by taking learning outside the classroom into the real-world context. In common with findings at other community colleges, this study identified inadequate language proficiency, particularly in speaking and listening skills, as a major barrier for ESL college learners seeking employment, or employers hiring and retaining immigrants as employees (CIITE, 2004; Palalas, 2009). As a result of these findings, language support was designed to provide English language instruction going beyond the standard 52-hour course: a hybrid English for Accounting course encompassing in-class, online and mobile-assisted ESP instruction. This paper reports on the pilot study of the mobile component of this re-designed course, which represents the first stage of an on-going Design-Based Research (DBR) study. Discussion is also offered of a new learning theory which we have called Ecological Constructivism (Hoven, 2008; Jakobsdottir, McKeown & Hoven, 2010), devised to incorporate the multiple dimensions of Ecological Linguistics and Constructivism in the situated and context-embedded learning engendered by these new uses of mobile devices.
Switch from 200 to 350 CD4 baseline count: what it means to HIV care and treatment programs in Kenya

INTRODUCTION
With the increasing population of infected individuals in Africa and constrained resources for care and treatment, antiretroviral management continues to be an important public health challenge. Since the announcement of World Health Organization recommendation and guidelines for initiation of antiretroviral Treatment at CD4 count below 350, many developing countries are adopting this strategy in their country specific guidelines to care and treatment of HIV and AIDS. Despite the benefits to these recommendations, what does this switch from 200 to 350 CD4 count mean in antiretroviral treatment demand?


METHODS
A Multi-centre study involving 1376 patients in health care settings in Kenya. CD4 count was carried out by flow cytometry among the HIV infected individuals in Kenya and results analyzed in view of the In-country and the new CD4 recommendation for initiation of antiretroviral treatment.


RESULTS
Across sites, 32% of the individual required antiretroviral at <200 CD4 Baseline, 40% at <250 baseline count and 58% based on the new criteria of <350 CD4 Count. There were more female (68%) than Male (32%).Different from <200 and <250 CD4 baseline criteria, over 50% of all age groups required antiretroviral at 350 CD4 baseline. Age groups between 41-62 led in demand for ART.


CONCLUSION
With the new guidelines, demand for ARVs has more than doubled with variations noted within regions and age groups. As A result, HIV Care and Treatment Programs should prepare for this expansion for the benefits to be realized.
Long-term nitroglycerin treatment is associated with supersensitivity to vasoconstrictors in men with stable coronary artery disease: prevention by concomitant treatment with captopril.

OBJECTIVES
We examined whether long-term nitroglycerin (NTG) treatment leads to an increase in sensitivity to vasoconstrictors. To assess a potential role of the renin-angiotensin system in mediating this phenomenon, we treated patients concomitantly with the angiotensin-converting enzyme (ACE) inhibitor captopril.


BACKGROUND
The anti-ischemic efficacy of organic nitrates is rapidly blunted by the development of nitrate tolerance. The underlying mechanisms are most likely multifactorial and may involve increased vasoconstrictor responsiveness.


METHODS
Forearm blood flow and vascular resistance were determined by using strain gauge plethysmography. The short-term responses to intraarterial angiotensin II (1, 3, 9 and 27 ng/min) and phenylephrine (an alpha-adrenergic agonist drug, 0.03, 0.1, 0.3 and 1 microg/min) were studied in 40 male patients with stable coronary artery disease. These patients were randomized into four groups receiving 48 h of treatment with NTG (0.5 microg/kg body weight per min) or placebo with or without the ACE inhibitor captopril (25 mg three times daily).


RESULTS
In patients treated with NTG alone, the maximal reductions in forearm blood flow in response to angiotensin II and phenylephrine were markedly greater (-64 +/- 3% and -53 +/- 4%, respectively) than those in patients receiving placebo (-41 +/- 2% and -42 +/- 2%, respectively). Captopril treatment completely prevented the NTG-induced hypersensitivity to angiotensin II and phenylephrine (-33 +/- 3% and -35 +/- 3%, respectively) but had no significant effect on blood flow responses in patients without NTG treatment (-34 +/- 2% and -37 +/- 3%, respectively).


CONCLUSIONS
We conclude that continuous administration of NTG is associated with an increased sensitivity to phenylephrine and angiotensin II that is prevented by concomitant treatment with captopril. The prevention of NTG-induced hypersensitivity to vasoconstrictors by ACE inhibition indicates an involvement of the renin-angiotensin system in mediating this phenomenon.
Transcranial direct current stimulation (tDCS) for treatment of major depression during pregnancy: study protocol for a pilot randomized controlled trial

BACKGROUND
Women with depression in pregnancy are faced with difficult treatment decisions. Untreated, antenatal depression has serious negative implications for mothers and children. While antidepressant drug treatment is likely to improve depressive symptoms, it crosses the placenta and may pose risks to the unborn child. Transcranial direct current stimulation is a focal brain stimulation treatment that improves depressive symptoms within 3 weeks of treatment by inducing changes to brain areas involved in depression, without impacting any other brain areas, and without inducing changes to heart rate, blood pressure or core body temperature. The localized nature of transcranial direct current stimulation makes it an ideal therapeutic approach for treating depression during pregnancy, although it has never previously been evaluated in this population.


METHODS/DESIGN
We describe a pilot randomized controlled trial of transcranial direct current stimulation among women with depression in pregnancy to assess the feasibility of a larger, multicentre efficacy study. Women over 18 years of age and between 14 and 32 weeks gestation can be enrolled in the study provided they meet diagnostic criteria for a major depressive episode of at least moderate severity and have been offered but refused antidepressant medication. Participants are randomized to receive active transcranial direct current stimulation or a sham condition that is administered in 15 30-minute treatments over three weeks. Women sit upright during treatment and receive obstetrical monitoring prior to, during and after each treatment session. Depressive symptoms, treatment acceptability, and pregnancy outcomes are assessed at baseline (prior to randomization), at the end of each treatment week, every four weeks post-treatment until delivery, and at 4 and 12 weeks postpartum.


DISCUSSION
Transcranial direct current stimulation is a novel therapeutic option for treating depression during pregnancy. This protocol allows for assessment of the feasibility of, acceptability of and adherence with a clinical trial protocol to administer this treatment to pregnant women with moderate to severe depression. Results from this pilot study will guide the development of a larger multicentre trial to definitively test the efficacy and safety of transcranial direct current stimulation for pregnant women with depression.


TRIAL REGISTRATION
Clinical Trials Gov NCT02116127.
Cloud-Assisted IoT-Based SCADA Systems Security: A Review of the State of the Art and Future Challenges

Industrial systems always prefer to reduce their operational expenses. To support such reductions, they need solutions that are capable of providing stability, fault tolerance, and flexibility. One such solution for industrial systems is cyber physical system (CPS) integration with the Internet of Things (IoT) utilizing cloud computing services. These CPSs can be considered as smart industrial systems, with their most prevalent applications in smart transportation, smart grids, smart medical and eHealthcare systems, and many more. These industrial CPSs mostly utilize supervisory control and data acquisition (SCADA) systems to control and monitor their critical infrastructure (CI). For example, WebSCADA is an application used for smart medical technologies, making improved patient monitoring and more timely decisions possible. The focus of the study presented in this paper is to highlight the security challenges that the industrial SCADA systems face in an IoT-cloud environment. Classical SCADA systems are already lacking in proper security measures; however, with the integration of complex new architectures for the future Internet based on the concepts of IoT, cloud computing, mobile wireless sensor networks, and so on, there are large issues at stakes in the security and deployment of these classical systems. Therefore, the integration of these future Internet concepts needs more research effort. This paper, along with highlighting the security challenges of these CI's, also provides the existing best practices and recommendations for improving and maintaining security. Finally, this paper briefly describes future research directions to secure these critical CPSs and help the research community in identifying the research gaps in this regard.
Study of the bronchodilating effect of three doses of nebulized oxitropium bromide in asthmatic preschool children using the forced oscillation technique

The aim of this study was to evaluate the bronchodilating capacity of nebulized oxitropium bromide (OB) in preschool asthmatic children and to determine an appropriate dose for usage in this age group. The trial enrolled 20 patients with moderate to severe stable asthma aged between 3.2 and 6.2 years (mean 4.7). Applying a placebo controlled, double-blind design, the effect of placebo was compared with three different doses of OB (375, 750 and 1500 μg) and with 400 μg fenoterol. The three different doses of OB resulted in a highly significant bronchodilation within 15 min after administration. The observed bronchodilation was comparable between the three doses during the first 2 h. However, after 4 h the lowest dose was significantly less powerful than the highest dose. Compared to the additional bronchodilation induced by fenoterol, no difference was found with the degree of bronchodilation of OB which occurred during the first 2 h. Furthermore, <%b>after 4 h only the lowest dose of OB was significantly less powerful than fenoterol assessed 10 min following a single 400 μg dose. Conclusion Oxitropium bromide is a potent and long-acting bronchodilator in preschool children at a dose of 750 μg and 1500 μg. No side-effects were observed. The exact duration of action remains uncertain, but even 4␣h after inhaling 750 or 1500 μg of OB no additive bronchodilation induced by fenoterol could be observed.
Pharmacokinetics, bioavailability and opioid effects of liquid versus tablet buprenorphine.

AIMS
Two tablet formulations of buprenorphine (a buprenorphine mono-product, Subutex, and a buprenorphine/naloxone combination product, Suboxone) are available for use in the treatment of opioid addiction; however, the bulk of the clinical studies supporting its approval by the US Food and Drug Administration (FDA) were conducted with a sublingual liquid preparation. To assist the clinician in interpreting the relevant literature in establishing dosing parameters for prescription of tablet buprenorphine, this study was designed to compare the steady state: (1) pharmacokinetics and bioavailability, and (2) physiological, subjective and objective opiate effects of two 8 mg buprenorphine tablets (16 mg) to those of 1 ml (8 mg/ml) buprenorphine solution based upon early reports suggesting that the bioavailability of the tablet was approximately 50% of that of the liquid.


DESIGN
Randomized, open-label, two-way crossover study.


SETTING
Inpatient hospitalization for 21 days.


PARTICIPANTS
Twenty-four male and females in general good health and meeting DSM-IV criteria for opiate dependence.


INTERVENTION
Subjects received one of the two buprenorphine formulations in the first 10-day period, and the other for the second 10-day period with no washout.


MEASUREMENTS
Pharmacokinetic analyses, opiate effects and adverse events.


FINDINGS
Drug steady state was reached by Day 7 of each 10-day period, area under the curve for 16 mg (two 8 mg) tablets was higher than the solution. The only non-kinetic statistically significant difference observed between the formulations was in changes in total opioid agonist score.


CONCLUSIONS
The serum concentration achieved by 16 mg of tablet buprenorphine is higher than that of the 8 mg solution, although differences between physiologic, subjective and objective opioid effects were not noted. The relative bioavailability of tablet versus solution is estimated to be 0.71; thus, with respect to dosing parameters for the tablet, clinicians should consider using less than 16 mg to achieve bioequivalence to the 8 mg solution.