Miracle-dz/UniFAR-FTUs huggingface dataset:
Allosteric control of an asymmetric transduction in a G protein-coupled receptor heterodimer

GPCRs play critical roles in cell communication. Although GPCRs can form heteromers, their role in signaling remains elusive. Here we used rat metabotropic glutamate (mGlu) receptors as prototypical dimers to study the functional interaction between each subunit. mGluRs can form both constitutive homo- and heterodimers. Whereas both mGlu2 and mGlu4 couple to G proteins, G protein activation is mediated by mGlu4 heptahelical domain (HD) exclusively in mGlu2-4 heterodimers. Such asymmetric transduction results from the action of both the dimeric extracellular domain, and an allosteric activation by the partially-activated non-functional mGlu2 HD. G proteins activation by mGlu2 HD occurs if either the mGlu2 HD is occupied by a positive allosteric modulator or if mGlu4 HD is inhibited by a negative modulator. These data revealed an oriented asymmetry in mGlu heterodimers that can be controlled with allosteric modulators. They provide new insight on the allosteric interaction between subunits in a GPCR dimer.
Contributing Factors for the Integration of Information and Communication Technology into Ethiopian Higher Education Institutions Teaching-Learning Practices

This paper is aimed at exploring the contributing factors for the integration of Information and Communication Technology (ICT) into higher education teaching-learning practices. For the study, a qualitative case study was used and the stakeholders from higher learning institutions were selected via purposive sampling. The data collected through interview and focus group discussions were analyzed using the QDA Miner Lite software. Information system theories such as the Technology Acceptance Model (TAM) and Technology, Organisation, and Environment (TOE) framework guided the discussion of the results. The findings showed that there are limited ICT resources for education in Ethiopian higher learning institutions and the limited resources are not used effectively. The challenges like insufficient ICT infrastructure, lack of skill, resistance to change, wrongly perceiving ICT as an additional burden, lack of cooperative work, and lack of policy for ICT integration into teaching-learning practices are identified as the contributing factors. Based on the discussion using TAM and the TOE framework, the researchers developed a conceptual framework guiding the integration of ICT into the higher education system of Ethiopia. The research suggested that the stakeholders involved in the education sector specifically, higher learning institutions, should follow the framework developed for ICT integration into their education system.
Ex post weighting of price data to estimate depreciation rates

To model economic depreciation, a database is used that contains information on assets discarded by companies. The acquisition and resale prices are known along with the length of use of these assets. However, the assets for which prices are known are only those that were involved in a transaction. While an asset depreciates on a continuous basis during its service life, the value of the asset is only known when there has been a transaction. This article proposes an ex post weighting to offset the effect of source of error in building econometric models.
Reaching older people with PA delivered in football clubs : the reach , adoption and implementation characteristics of the Extra Time Programme BMC Public Health Sample

Background Older adults (OA) represent a core priority group for physical activity and Public Health policy. As a result, significant interest is placed on how to optimise adherence to interventions promoting these approaches. Extra Time (ET) is an example of a national programme of physical activity interventions delivered in professional football clubs for OA aged 55+ years. This paper aims to examine the outcomes from ET, and unpick the processes by which these outcomes were achieved.
Human-robot cooperative movement training : Learning a novel sensory motor transformation during walking with robotic assistance-as-needed

Background: A prevailing paradigm of physical rehabilitation following neurologic injury is to "assist-asneeded" in completing desired movements. Several research groups are attempting to automate this principle with robotic movement training devices and patient cooperative algorithms that encourage voluntary participation. These attempts are currently not based on computational models of motor learning. Methods: Here we assume that motor recovery from a neurologic injury can be modelled as a process of learning a novel sensory motor transformation, which allows us to study a simplified experimental protocol amenable to mathematical description. Specifically, we use a robotic force field paradigm to impose a virtual impairment on the left leg of unimpaired subjects walking on a treadmill. We then derive an "assist-as-needed" robotic training algorithm to help subjects overcome the virtual impairment and walk normally. The problem is posed as an optimization of performance error and robotic assistance. The optimal robotic movement trainer becomes an error-based controller with a forgetting factor that bounds kinematic errors while systematically reducing its assistance when those errors are small. As humans have a natural range of movement variability, we introduce an error weighting function that causes the robotic trainer to disregard this variability. Results: We experimentally validated the controller with ten unimpaired subjects by demonstrating how it helped the subjects learn the novel sensory motor transformation necessary to counteract the virtual impairment, while also preventing them from experiencing large kinematic errors. The addition of the error weighting function allowed the robot assistance to fade to zero even though the subjects' movements were variable. We also show that in order to assist-as-needed, the robot must relax its assistance at a rate faster than that of the learning human. Conclusion: The assist-as-needed algorithm proposed here can limit error during the learning of a dynamic motor task. The algorithm encourages learning by decreasing its assistance as a function of the ongoing progression of movement error. This type of algorithm is well suited for helping people learn dynamic tasks for which large kinematic errors are dangerous or discouraging, and thus may prove useful for robot-assisted movement training of walking or reaching following neurologic injury. Published: 28 March 2007 Journal of NeuroEngineering and Rehabilitation 2007, 4:8 doi:10.1186/1743-0003-4-8 Received: 20 April 2006 Accepted: 28 March 2007 This article is available from: http://www.jneuroengrehab. com/content/4/1/8 © 2007 Emken et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
2 How Can Haptic Vector Fields Control Animations ? 2 . 1 Overview

We are developing paradigms and algorithms for browsing and editing families of animations using a haptic forcefeedback device called a Phantom. These techniques may be generalized to navigation of any high degree-offreedom system from a lower degree-of-freedom control space, with applications to telerobotics and simulation of virtual humans. We believe that modeling the animation configuration space coupled with the highly interactive nature of the haptic device provides us with useful and intuitive means of control. We have implemented our ideas in a system for the manipulation of animation motion capture data; in particular, anthropomorphic figures with 57 degrees of freedom are controlled by the user in real time. We treat trajectories, which encode animation, as first-class objects; haptic manipulation of these trajectories results in change to the animation. We have several haptic editing modes in which these trajectories are either haptically deformed or performed by the user with expressive control subject to dynamic haptic constraints. The initial trajectories are given by sample animations (for example, motion capture data) but may be authored by other means.
The Strengthening Exercises in Shoulder Impingement trial (The SExSI-trial) investigating the effectiveness of a simple add-on shoulder strengthening exercise programme in patients with long-lasting subacromial impingement syndrome: Study protocol for a pragmatic, assessor blinded, parallel-group, r

Background: Subacromial impingement syndrome (SIS) is a painful, and often long lasting, shoulder condition affecting patient function and quality of life. In a recent study, we observed major strength impairments in shoulder external rotation and abduction (~30%) in a population of patients with pronounced and long-lasting SIS. However, the current rehabilitation of such strength impairments may be inadequate, with novel rehabilitation programmes including exercise therapy only improving external rotation strength by 4–13%. As these previous studies are the basis of current practice, this suggests that the strengthening component could be inadequate in the rehabilitation of these patients, and it seems likely that more emphasis should be placed on intensifying this part of the rehabilitation. The purpose of this study is to investigate the effectiveness of a programme consisting of progressive home-based resistance training using an elastic band, aimed at improving shoulder external rotation and abduction strength, added to usual care and initiated shortly after diagnosis has been established. (Continued on next page) * Correspondence: mibc@phmetropol.dk Department of Physiotherapy and Occupational Therapy, Faculty of Health and Technology, Metropolitan University College, Sigurdsgade 26, DK-2200 Copenhagen N, Denmark Sports Orthopaedic Research Center – Copenhagen (SORC-C), Department of Orthopedic Surgery, Copenhagen University Hospital, Amager-Hvidovre, Kettegårds Allé 30, DK-2650 Hvidovre, Denmark Full list of author information is available at the end of the article © The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Clausen et al. Trials (2018) 19:154 https://doi.org/10.1186/s13063-018-2509-7
Should NS5A inhibitors serve as the scaffold for all-oral anti-HCv combination therapies?

: Chronic hepatitis C virus (HCV) infection represents a global health problem that affects up to 130–150 million people worldwide. The HCV treatment landscape has been transformed recently by the introduction of direct-acting antiviral (DAA) agents that target viral proteins, including the NS3 protease, the NS5B polymerase, and the NS5A protein. Treatment with multiple DAAs in combination has been shown to result in high rates of sustained virologic response, without the need for pegylated interferon, and a shorter duration of therapy compared with interferon-based regimens; however, the optimal combination of DAAs has yet to be determined. The class of NS5A inhibitors has picomolar potency with pangenotypic activity, and recent clinical studies have shown these inhibitors to be an important component of DAA combination regimens. This review discusses the rational design of an optimal anti-HCV DAA cocktail, with a focus on the role of NS5A in the HCV life cycle, the attributes of the NS5A class of inhibitors, and the potential for NS5A inhibitors to act as a scaffold for DAA-only treatment regimens.
Pleiotropy between neuroticism and physical and mental health: findings from 108 038 men and women in UK Biobank

There is considerable evidence that people with higher levels of the personality trait neuroticism have an increased risk of several types of mental disorder. Higher neuroticism has also been associated, less consistently, with increased risk of various physical health outcomes. We hypothesised that these associations may, in part, be due to shared genetic influences. We tested for pleiotropy between neuroticism and 12 mental and physical diseases or health traits using linkage disequilibrium regression and polygenic profile scoring. Genetic correlations were derived between neuroticism scores in 108 038 people in UK Biobank and health-related measures from 12 large genome-wide association studies (GWAS). Summary information for the 12 GWAS was used to create polygenic risk scores for the health-related measures in the UK Biobank participants. Associations between the health-related polygenic scores and neuroticism were examined using regression, adjusting for age, sex, genotyping batch, genotyping array, assessment centre, and population stratification. Genetic correlations were identified between neuroticism and anorexia nervosa (rg = 0.17), major depressive disorder (rg = 0.66) and schizophrenia (rg = 0.21). Polygenic risk for several health-related measures were associated with neuroticism, in a positive direction in the case of bipolar disorder (β = 0.017), major depressive disorder (β = 0.036), schizophrenia (β = 0.036), and coronary artery disease (β = 0.011), and in a negative direction in the case of BMI (β = −0.0095). These findings indicate that a high level of pleiotropy exists between neuroticism and some measures of mental and physical health, particularly major depressive disorder and schizophrenia.
The Current State of Blockchain Consensus Mechanism: Issues and Future Works

—Blockchain is a decentralized ledger that serves as the foundation of Bitcoin and has found applications in various domains due to its immutable properties. It has the potential to change digital transactions drastically. It has been successfully used across multiple fields for record immutability and reliability. The consensus mechanism is the backbone of blockchain operations and validates newly generated blocks before they are added. To verify transactions in the ledger, various peer-to-peer (P2P) network validators use different consensus algorithms to solve the reliability problem in a network with unreliable nodes. The security and reliability of the inherent consensus algorithm used mainly determine blockchain security. However, consensus algorithms consume significant resources for validating new nodes. Therefore the safety and reliability of a blockchain system is based on the consensus mechanism's reliability and performance. Although various consensus mechanisms/algorithms exist, there is no unified evaluation criterion to evaluate them. Evaluating the consensus algorithm will explain system reliability and provide a mechanism for choosing the best consensus mechanism for a defined set of problems. This article comprehensively analyzes existing and recent consensus algorithms' throughput, scalability, latency, energy efficiency, and other factors such as attacks, Byzantine fault tolerance, adversary tolerance, and decentralization levels. The paper defines consensus mechanism criteria, evaluates available consensus algorithms based on them, and presents their advantages and disadvantages.
Prenatal exposure to maternal smoking and offspring DNA methylation across the lifecourse: findings from the Avon Longitudinal Study of Parents and Children (ALSPAC)

Maternal smoking during pregnancy has been found to influence newborn DNA methylation in genes involved in fundamental developmental processes. It is pertinent to understand the degree to which the offspring methylome is sensitive to the intensity and duration of prenatal smoking. An investigation of the persistence of offspring methylation associated with maternal smoking and the relative roles of the intrauterine and postnatal environment is also warranted. In the Avon Longitudinal Study of Parents and Children, we investigated associations between prenatal exposure to maternal smoking and offspring DNA methylation at multiple time points in approximately 800 mother–offspring pairs. In cord blood, methylation at 15 CpG sites in seven gene regions (AHRR, MYO1G, GFI1, CYP1A1, CNTNAP2, KLF13 and ATP9A) was associated with maternal smoking, and a dose-dependent response was observed in relation to smoking duration and intensity. Longitudinal analysis of blood DNA methylation in serial samples at birth, age 7 and 17 years demonstrated that some CpG sites showed reversibility of methylation (GFI1, KLF13 and ATP9A), whereas others showed persistently perturbed patterns (AHRR, MYO1G, CYP1A1 and CNTNAP2). Of those showing persistence, we explored the effect of postnatal smoke exposure and found that the major contribution to altered methylation was attributed to a critical window of in utero exposure. A comparison of paternal and maternal smoking and offspring methylation showed consistently stronger maternal associations, providing further evidence for causal intrauterine mechanisms. These findings emphasize the sensitivity of the methylome to maternal smoking during early development and the long-term impact of such exposure.
Characterization of non-Darcy multiphase flow in petroleum bearing formations

The objectives of this research are: Develop a proper theoretical model for characterizing non-Darcy multi-phase flow in petroleum bearing formations. Develop an experimental technique for measuring non-Darcy flow coefficients under multiphase flow at insitu reservoir conditions. Develop dimensional consistent correlations to express the non-Darcy flow coefficient as a function of rock and fluid properties for consolidated and unconsolidated porous media. The research accomplished during the period May 1991--May 1992 focused upon theoretical and experimental studies of multiphase non-Darcy flow in porous media.
Development of novel rosuvastatin nanostructured lipid carriers for oral delivery in an animal model

Objective: The aim of this study was to prepare rosuvastatin nanostructured lipid carriers (RST-NLCs) in order to increase the bioavailability of RST. Materials and methods: RST-NLCs were prepared by hot melt high-pressure homogenization method. The physicochemical parameters of RST-NLCs were characterized in terms of particle size, zeta potential, morphology, entrapment efficiency, and in vitro release behavior. Results: The mean particle size was found to be 98.4 ± 0.3 nm. The entrapment efficiency was 84.3% ± 1.3%. The RST was slowly released from NLCs over a period of 48 h in the PBS. A similar phenomenon was also observed in a pharmacokinetic study in rats, in which the area under the curve of NLCs was 1.65-fold higher than that of tablet powder. Conclusion: The results of pharmacodynamics showed that the effective lipid-lowering activity of NLCs could be explained by the fact that NLCs resulted in sustained release of RST, which could have increased absorption and provided a higher bioavailability.
Usefulness of the 6-minute walk test as a screening test for pulmonary arterial enlargement in COPD

Purpose: Pulmonary hypertension and exercise-induced oxygen desaturation (EID) influence acute exacerbation of COPD. Computed tomography (CT)-detected pulmonary artery (PA) enlargement is independently associated with acute COPD exacerbations. Associations between PA to aorta (PA:A) ratio and EID in patients with COPD have not been reported. We hypothesized that the PA:A ratio correlated with EID and that results of the 6-minute walk test (6MWT) would be useful for predicting the risk associated with PA:A . 1. Patients and methods: We retrospectively measured lung function, 6MWT, emphysema area, and PA enlargement on CT in 64 patients with COPD. The patients were classified into groups with PA:A # 1 and . 1. Receiver-operating characteristic curves were used to determine the threshold values with the best cutoff points to predict patients with PA:A . 1. Results: The PA:A . 1 group had lower forced expiratory volume in 1 second (FEV 1 ), forced vital capacity (FVC), FEV 1 :FVC ratio, diffusion capacity of lung carbon monoxide, 6MW distance, and baseline peripheral oxygen saturation (SpO 2 ), lowest SpO 2 , highest modified Borg scale results, percentage low-attenuation area, and history of acute COPD exacerbations # 1 year, and worse BODE (Body mass index, airflow Obstruction, Dyspnea, and Exercise) index results ( P , 0.05). Predicted PA:A . 1 was determined for SpO 2 during 6MWT (best cutoff point 89%, area under the curve 0.94, 95% confidence interval 0.88–1). SpO 2 , 90% during 6MWT showed a sensitivity of 93.1, specificity of 94.3, positive predictive value of 93.1, negative predictive value of 94.3, positive likelihood ratio of 16.2, and negative likelihood ratio of 0.07. Conclusion: Lowest SpO 2 during 6MWT may predict CT-measured PA:A, and lowest SpO 2 , 89% during 6MWT is excellent for detecting pulmonary hypertension in COPD. mMRC, modified Medical Research Council; BODE, body mass index, obstruction (airflow), dyspnea, and exercise; FEV 1 , forced expiratory volume in 1 second; FVC, forced vital capacity; D lCO , diffusion capacity of lung carbon monoxide; rV, residual volume; TlC, total lung capacity; laa, low-attenuation area; 6MWD, 6-minute walking distance; spO 2 , peripheral oxygen saturation; Pr, pulse rate.
Effective Leadership: Bringing Mentoring and Creativity to the Principalship

In education today there is a growing appreciation for the significance of effective in-school leadership. In addition, one can appreciate the fact that little effort is being made toward improving ways for preparing principals for this critical leadership role. This article explores behaviors that constitute effective leadership and suggests that mentoring combined with creativity have the potential to positively affect leadership styles.