Miracle-dz/UniFAR-FTUs huggingface dataset:
Role of the Sequence Surrounding Predicted Transmembrane Helix M4 in Membrane Association and Function of the Ca2+ Release Channel of Skeletal Muscle Sarcoplasmic Reticulum (Ryanodine Receptor Isoform 1)*

The role of the sequence surrounding M4 in ryanodine receptors (RyR) in membrane association and function was investigated. This sequence contains a basic, 19-amino acid M3/M4 loop, a hydrophobic 44–49 amino acid sequence designated M4 (or M4a/M4b), and a hydrophilic M4/M5 loop. Enhanced green fluorescent protein (EGFP) was inserted into RyR1 and truncated just after the basic sequence, just after M4, within the M4/M5 loop, just before M5 and just after M5. The A52 epitope was inserted into RyR2 and truncated just after M4a. Analysis of these constructs ruled out a M3/M4 transmembrane hairpin and narrowed the region of membrane association to M4a/M4b. EGFP inserted between M4a and M4b in full-length RyR2 was altered conformationally, losing fluorescence and gaining trypsin sensitivity. Although it was accessible to an antibody from the cytosolic side, tryptic fragments were membrane-bound. The expressed protein containing EGFP retained caffeine-induced Ca2+ release channel function. These results suggest that M4a/M4b either forms a transmembrane hairpin or associates in an unorthodox fashion with the cytosolic leaflet of the membrane, possibly involving the basic M3/M4 loop. The expression of a mutant RyR1, Δ4274–4535, deleted in the sequence surrounding both M3 and M4, restored robust, voltage-gated L-type Ca2+ currents and Ca2+ transients in dyspedic myotubes, demonstrating that this sequence is not required for either orthograde (DHPR activation of sarcoplasmic reticulum Ca2+ release) or retrograde (RyR1 increase in DHPR Ca2+ channel activity) signals of excitation-contraction coupling. Maximal amplitudes of L-currents and Ca2+ transients with Δ4274–4535 were larger than with wild-type RyR1, and voltage-gated sarcoplasmic reticulum Ca2+ release was more sensitive to activation by sarcolemmal voltage sensors. Thus, this region may act as a negative regulatory module that increases the energy barrier for Ca2+ release channel opening.
Delivering discontinuous innovation through modularity: The case of Chinese electric vehicle industry

The emerging alternative engine technologies with high environmental performance have increasingly gained managerial attention in the global automobile industry during the past two decades. These technologies, incorporating with other components ones, give rise to the creation of new energy vehicles. This paper explores how to deliver discontinuous innovation through cross-industry integration of previously distinct modular technologies. In contrast to much current research on modularity or discontinuous innovation individually, we propose a strategic framework linking modularity with discontinuous innovation together based on case study. We argue that discontinuous innovation can be achieved by establishing an industry platform enabled by modular product architecture. The industry platform demands not only introducing new compatible technologies in essential components or subsystems of the whole product system in order to substitute for the counterparts in the existent dominant design but also establishing universal interface to re-architect the relationships between the new core components and other parts. We contend that discontinuous innovation involves variety of knowledge bases and technological capabilities spanning over a range of fields. We empirically examine this framework from the development of electric vehicle industry in China.
Human Chest Wall Function while Awake and during Halothane Anesthesia: I. Quiet Breathing

Background Data concerning chest wall configuration and the activities of the major respiratory muscles that determine this configuration during anesthesia in humans are limited. The aim of this study was to determine the effects of halothane anesthesia on respiratory muscle activity and chest wall shape and motion during spontaneous breathing. Methods Six human subjects were studied while awake and during 1 MAC halothane anesthesia. Respiratory muscle activity was measured using fine‐wire electromyography electrodes. Chest wall configuration was determined using images of the thorax obtained by three‐dimensional fast computed tomography. Tidal changes in gas volume were measured by integrating respiratory gas flow, and the functional residual capacity was measured by a nitrogen dilution technique. Results While awake, ribcage expansion was responsible for 25 plus/minus 4% (mean plus/minus SE) of the total change in thoracic volume (Delta Vth) during inspiration. Phasic inspiratory activity was regularly present in the diaphragm and parasternal intercostal muscles. Halothane anesthesia (1 MAC) abolished activity in the parasternal intercostal muscles and increased phasic expiratory activity in the abdominal muscles and lateral ribcage muscles. However, halothane did not significantly change the ribcage contribution to Delta Vth (18 plus/minus 4%). Intrathoracic blood volume, measured by comparing changes in total thoracic volume and gas volume, increased significantly during inspiration both while awake and while anesthetized (by approximately 20% of Delta Vth, P < 0.05). Halothane anesthesia significantly reduced the functional residual capacity (by 258 plus/minus 78 ml), primarily via an inward motion of the end‐expiratory position of the ribcage. Although the diaphragm consistently changed shape, with a cephalad displacement of posterior regions and a caudad displacement of anterior regions, the diaphragm did not consistently contribute to the reduction in the functional residual capacity. Halothane anesthesia consistently increased the curvature of the thoracic spine measured in the sagittal plane. Conclusions The authors conclude that (1) ribcage expansion is relatively well preserved during halothane anesthesia despite the loss of parasternal intercostal muscle activity; (2) an inward displacement of the ribcage accounts for most of the decrease in functional residual capacity caused by halothane anesthesia, accompanied by changes in diaphragm shape that may be related to motion of its insertions on the thoracoabdominal wall; and (3) changes in intrathoracic blood volume constitute a significant fraction of Delta Vth during tidal breathing.
A neurotensin analog blocks cocaine-conditioned place preference and reinstatement

Neurotensin (NT) is a neuropeptide that acts as a neurotransmitter and neuromodulator in the central nervous system. Several studies suggest a therapeutic role for NT analogs in nicotine and other psychostimulant addictions. We studied the effects of the nonselective NT receptor agonist NT69L, which has equal affinity for the two major NT receptors, NTS1 and NTS2, on the expression of cocaine-conditioned place preference (cocaine-CPP) and reinstatement after extinction. Robust cocaine-CPP was obtained after 5 days of conditioning. Extinction was induced using eight repeated daily injections of saline. Reinstatement was prompted by priming with one injection of cocaine (12 mg/kg intraperitoneally). On the test day, NT69L (1 mg/kg intraperitoneally) was administered 30 min before assessing cocaine-CPP. Extinction led to the loss of cocaine-CPP. One injection of cocaine (12 mg/kg intraperitoneally) for cocaine priming reinstated cocaine-CPP. NT69L blocked cocaine-CPP reinstatement in cocaine-primed animals. In addition, NT69L blocked cocaine-CPP reinstatement when administered before priming with cocaine. Thus, the NT agonist NT69L blocked both cocaine-CPP and reinstatement to cocaine preference. NT69L may exert this action by modulating the mesocorticolimbic dopamine and glutamatergic pathways involved in addiction and relapse processes. Therefore, NT agonists may represent a novel therapy for the treatment of addiction to cocaine and possibly to other psychostimulants.
Call to action? Survey highlights the shortcomings of business-as-usual in addressing gender equality in the fishery sector

In the fishery sector, too little attention is paid to gender equality, and gender-blind policies and programmes render the issue as peripheral or invisible. Since 1990, the Asian Fisheries Society (AFS) has paid sustained attention to gender, although at a modest level. In order to gauge how the small cadre of gender experts perceived progress in mobilising attention and action on gender in fisheries, we conducted an online structured survey. Using Actor Network Theory as the questionnaire framework, we analysed the responses from 41 experts. The respondents perceived that the understanding of the gender inequality issues has progressed well but the strategic messages arising are not communicated strongly nor well targeted. Few workers, and even fewer full time professionals, are dedicated to the field of gender research and action, and research is not well linked to grassroots needs. Therefore, the field suffers from weak efforts to enroll more champions, leaders and actors and reach critical mass for mobilisation for gender equality. For mobilisation to happen, targeted, dedicated resources are urgently needed, including full time people, institutional support and projects. To achieve this will require strong, perhaps even confrontational, campaigns and plans, from within the fishery sector, led by a self-nominated core group of committed women and men concerned with inequality in the fishery sector.
Returns to Schooling in Bangladesh Revisited: An Instrumental Variable Quantile Regression Approach

The paper focuses on estimation of returns to schooling in the Bangladesh context. Earlier studies which tried to quantify the returns were constrained by a number of factors including the limitations of the measurement techniques that were deployed. This paper revisits the issue and makes an attempt to build on earlier scholarly works through application of quantile regression and instrumental variable quantile regression methods. The paper finds that endogeneity problem leads to underestimation of the returns to schooling, and that the returns tend to vary along the wage distribution, which mean regression models fail to capture. The analysis shows that average returns to schooling for female is higher than that of male. The analysis also shows that returns to schooling tends to be higher as one moves along higher percentiles of wage distribution. This is found to be true both for male and female, as also for rural and urban labour markets.
An Efficient Algorithm for Mining Large Item Sets

It propose online mining algorithm ( OMA) which online discover large item sets. Without pre-setting a default threshold, the OMA algorithm achieves its efficiency and threshold-flexibility by calculating item-setspsila counts. It is unnecessary and independent of the default threshold and can flexibly adapt to any userpsilas input threshold. In addition, we propose cluster-based association rule algorithm (CARA) creates cluster tables to aid discovery of large item sets. It only requires a single scan of the database, followed by contrasts with the partial cluster tables. It not only prunes considerable amounts of data reducing the time needed to perform data scans and requiring less contrast, but also ensures the correctness of the mined results. By using the CARA algorithm to create cluster tables in advance, each CPU can be utilized to process a cluster table; thus large item sets can be immediately mined even when the database is very large.
In Vitro Methods of Assessing Renal Damage

Freshly isolated and primary cultures of rat kidney cells derived from specific nephron segments can be useful in vitro models for studying processes such as drug metabolism, membrane transport, and biochemical mechanisms of chemically induced toxicity. Proximal tubular (PT) and distal tubular (DT) cells were isolated from rat renal cortex by collagenase perfusion and Percoll density-gradient centrifugation. Oxidants produced glutathione (GSH) oxidation and lipid peroxidation and were markedly more cytotoxic to DT cells than to PT cells. Similarly, alkylating agents that target soft nucleophiles such as GSH and protein sulfhydryls were more toxic to DT cells than to PT cells, whereas an alkylating agent that targets hard nucleophiles was equally cytotoxic in the 2 cell types. DT cells were also more sensitive to brief periods of oxygen deprivation and were markedly more susceptible to ATP depletion by treatment with iodoacetate and cyanide than were PT cells. Serum-free, hormonally defined conditions have been optimized for primary culture of rat renal PT and DT cells to maintain differentiated function for up to 9 days. Primary cultures exhibited similar susceptibilities as freshly isolated cells to acute injury from chemical toxicants and the cultures express several isoforms of cytochrome P-450. These studies show that freshly isolated and primary cultures of rat renal PT and DT cells can be used to study both short-term and long-term responses to toxic chemicals.
Simplicity and Efficiency of Integrate-and-Fire Neuron Models

Lovelace and Cios (2008) recently proposed a very simple spiking neuron (VSSN) model for simulations of large neuronal networks as an efficient replacement for the integrate-and-fire neuron model. We argue that the VSSN model falls behind key advances in neuronal network modeling over the past 20 years, in particular, techniques that permit simulators to compute the state of the neuron without repeated summation over the history of input spikes and to integrate the subthreshold dynamics exactly. State-of-the-art solvers for networks of integrate-and-fire model neurons are substantially more efficient than the VSSN simulator and allow routine simulations of networks of some 105 neurons and 109 connections on moderate computer clusters.
Long nerve gaps limit the regenerative potential of bioartificial nerve conduits filled with Schwann cells.

PURPOSE Recently we successfully used a conduit of epsilon-caprolactone-co-trimethylene carbonate filled with Schwann cells (SC) across a 20 mm gap in a rat median nerve. In this study we applied the tubes with SC across a 40 mm gap in order to analyse the regenerative potential of the tubes in long nerve defects. METHODS To augment the nerve defect a cross-chest procedure was used and the tubes were implanted with injected isogeneic SCs inside (group 3). Both ulnar nerves were used for a 40 mm autograft (group 2). For control group non-operated animals were used (group 1). The grasping test, histology (S-100, PAM), electrophysiology, and the muscle weight were used to assess regeneration. RESULTS After 12 months, grasping was seen only in three animals of group 3 (3.6 g [95% CI: 0 to 7.6 g]). However, in group 2 all rats had a partial functional regeneration (42.8 g [95% CI: 39.1 to 46.6 g]). The grasping force of the non-operated animals (group 1) was 240.9 g [95% CI: 237.2 to 244.7 g] at the time. Histology from group 3 confirmed an irregular arrangement of fibres in contrast to more organized structures in group 2. Electrophysiology in group 3 displayed potentials only in the three animals with functional regeneration. In group 2 all animals exhibited potentials. A significant decrease of muscle weight was observed in groups 2 and 3, most prominent in the latter. CONCLUSION Regeneration was not successful across the 40 mm gap using the applied tube in combination with SC. For future experiments further consideration should be taken in optimizing the cellular and material components that are critical for a successful application to overcome very large nerve gaps.
Modelling the inhibitory effect of copper sulfate on the growth of Penicillium expansum and Botrytis cinerea

Aims: This study aimed to investigate the effect of copper sulfate (from 0 to 8 mmol kg−1) on radial growth rate and lag time of two moulds responsible for vine grapes spoilage: Penicillium expansum strain 25·03 and Botrytis cinerea, strains BC1 and BC2.
Across the pond: alternative ways of obtaining scholarly articles and the impact on traditional publishing models, from a UK/European perspective

This column examines the growth and impact of open access (OA) with emphasis on a UK/European perspective. It considers the various colors of OA, the impact on authors, institutions, and funders, and speculates on the future of traditional academic publishing. The author considers the pros and cons of a variety of OA methods--including the so-called ‘guerrilla OA’ services and sites-- and discusses the current mandates in place for the UK’s upcoming Research Excellence Framework exercise, which will report back on the research outputs produced in universities between 2014-2020.
Processes Inherent in Mammography-Screening Decisions of Rarely or Never-Screened Women

Breast cancer is a significant cause of mortality and morbidity. A strong association exists between survival and early detection through regular mammography. Impoverished women underuse this life-saving screening, resulting in a disproportionate cancer burden. The study purpose is to discover the process of rarely or never-screened women’s mammography-screening decisions. The sample consists of five rural, low-income, uninsured, and rarely or never-screened women. Grounded theory methodology is used to generate a new theoretical explanation of mammography-screening decision making. Findings include the central conceptual categories, intuitive dominance and intuitive certainty, which contribute toward an intuitive decision-making default. This intuitive thinking style weaves throughout two interrelated categories: (a) scarce, supportive, relational resources for learning and (b) dichotomous health care—seeking behaviors. Implications focus on a nontraditional client assessment whereby nurses can facilitate relational-based knowledge construction. Recommendations for future research include examination of the process of integrating intuition with reasoned thought for more fully informed decisions.
Does a prosthodontist spend more time providing mandibular two-implant overdentures than conventional dentures?

PURPOSE In this article, the time taken by a prosthodontist to fabricate and maintain mandibular overdentures retained by two implants and conventional dentures is compared. MATERIALS AND METHODS Sixty edentulous patients between the ages of 65 and 75 completed a randomized clinical trial. All received new maxillary conventional dentures and either a mandibular conventional denture (n = 30) or a two-implant overdenture on ball attachments (n = 30). The time spent by the prosthodontist and the number of visits required for treatment, including both scheduled and unscheduled visits, were recorded for each patient from preliminary impressions to 6 months following delivery. Data from the two groups were compared using Mann-Whitney U tests. RESULTS The prosthodontist spent a mean total time of 296 minutes in treating an implant overdenture patient and 282 minutes on a conventional denture patient during the period from preliminary impressions to the 6-month follow-up. The mean numbers of appointments were 10.1 (implant group) and 10.8 (conventional group). These differences were not significant. CONCLUSION Although additional knowledge is required to treat patients with implant prostheses, the time required by the prosthodontist to provide two-implant mandibular overdentures with ball attachments was not significantly different than the time needed for conventional denture treatment.
Prevalence of Carotid Atherosclerosis in Diabetic Patients Ultrasound high-resolution B-mode imaging on carotid arteries

OBJECTIVE To quantitatively assess atherosclerosis of the carotid artery in subjects with and without diabetes. RESEARCH DESIGN AND METHODS Ultrasound high resolution B-mode imaging of carotid arteries was conducted on 71 nondiabetic subjects without hyperlipidemia or hypertension and 295 diabetic patients to determine IMT of the arterial wall. RESULTS IMT was linearly related with age in nondiabetic (IMT = [0.0087 × age] + 0.3318) and diabetic subjects (IMT = [0.0155 × age] + 0.32450). The regression coefficient for age was significantly greater in diabetic than nondiabetic subjects. IMT (mean ± SD) of diabetic subjects aged 20–29 was significantly > that of nondiabetic subjects aged 20–29 (0.73 ± 0.27 vs. 0.52 ± 0.07 mm, P < 0.01). Multivariate regression analysis of 275 NIDDM patients indicated smoking, hyperlipidemia, duration of diabetes, hypertension, and age were factors determining thickness of the carotid arterial wall. CONCLUSIONS Diabetes, along with age, hyperlipidemia, smoking, and hypertension, aggravates carotid atherosclerosis.
Value of dynamic ³¹P magnetic resonance spectroscopy technique in in vivo assessment of the skeletal muscle mitochondrial function in type 2 diabetes.

BACKGROUND Phosphorous magnetic resonance spectroscopy ((31)P-MRS) has been successfully applied to study intracellular membrane compounds and high-energy phosphate metabolism. This study aimed to evaluate the capability of dynamic (31)P-MRS for assessing energy metabolism and mitochondrial function in skeletal muscle from type 2 diabetic patients. METHODS Dynamic (31)P-MRS was performed on 22 patients with type 2 diabetes and 26 healthy volunteers. Spectra were acquired from quadriceps muscle while subjects were in a state of rest, at exercise and during recovery. The peak areas of inorganic phosphate (Pi), phosphocreatine (PCr), and adenosine triphosphate (ATP) were measured. The concentration of adenosine diphosphate (ADP) and the intracellular pH value were calculated from the biochemistry reaction equilibrium. The time constant and recovery rates of Pi, PCr, and ADP were analyzed using exponential curve fitting. RESULTS As compared to healthy controls, type 2 diabetes patients had significantly lower skeletal muscle concentrations of Pi, PCr and β-ATP, and higher levels of ADP and Pi/PCr. During exercise, diabetics experienced a significant Pi peak increase and PCr peak decrease, and once the exercise was completed both Pi and PCr peaks returned to resting levels. Quantitatively, the mean recovery rates of Pi and PCr in diabetes patients were (10.74 ± 1.26) mmol/s and (4.74 ± 2.36) mmol/s, respectively, which was significantly higher than in controls. CONCLUSIONS Non-invasive quantitative (31)P-MRS is able to detect energy metabolism inefficiency and mitochondrial function impairment in skeletal muscle of type 2 diabetics.