Miracle-dz/UniFAR-FTUs huggingface dataset:
PGC-1α regulates the neuromuscular junction program and ameliorates Duchenne muscular dystrophy

The coactivator PGC-1α mediates key responses of skeletal muscle to motor nerve activity. We show here that neuregulin-stimulated phosphorylation of PGC-1α and GA-binding protein (GABP) allows recruitment of PGC-1α to the GABP complex and enhances transcription of a broad neuromuscular junction gene program. Since a subset of genes controlled by PGC-1α and GABP is dysregulated in Duchenne muscular dystrophy (DMD), we examined the effects of transgenic PGC-1α in muscle of mdx mice. These animals show improvement in parameters characteristic of DMD, including muscle histology, running performance, and plasma creatine kinase levels. Thus, control of PGC-1α levels in skeletal muscle could represent a novel avenue to prevent or treat DMD.
PHD - an automatic mail server for protein secondary structure prediction

By the middle of 1993, > 30,000 protein sequences has been listed. For 1000 of these, the three-dimensional (tertiary) structure has been experimentally solved. Another 7000 can be modelled by homology. For the remaining 21,000 sequences, secondary structure prediction provides a rough estimate of structural features. Predictions in three states range between 35% (random) and 88% (homology modelling) overall accuracy. Using information about evolutionary conservation as contained in multiple sequence alignments, the secondary structure of 4700 protein sequences was predicted by the automatic e-mail server PHD. For proteins with at least one known homologue, the method has an expected overall three-state accuracy of 71.4% for proteins with at least one known homologue (evaluated on 126 unique protein chains).
Regulation of CLV3 Expression by Two Homeobox Genes in Arabidopsis1

The ability of meristems to continuously produce new organs depends on the activity of their stem cell populations, which are located at the meristem tip. In Arabidopsis, the size of the stem cell domain is regulated by two antagonistic activities. TheWUS (WUSCHEL) gene, encoding a homeodomain protein, promotes the formation and maintenance of stem cells. These stem cells express CLV3(CLAVATA3), and signaling of CLV3 through the CLV1/CLV2 receptor complex restricts WUS activity. Homeostasis of the stem cell population may be achieved through feedback regulation, whereby changes in stem cell number result in corresponding changes inCLV3 expression levels, and adjustment ofWUS expression via the CLV signal transduction pathway. We have analyzed whether expression ofCLV3 is controlled by the activity of WUSor another homeobox gene, STM (SHOOT MERISTEMLESS), which is required for stem cell maintenance. We found that expression of CLV3 depends onWUS function only in the embryonic shoot meristem. At later developmental stages, WUS promotes the level ofCLV3 expression, together with STM. Within a meristem, competence to respond to WUS activity by expressing CLV3 is restricted to the meristem apex.
Graph-based Cluster Analysis to Identify Similar Questions: A Design Science Approach

Social question answering (SQA) services allow users to clarify their queries by asking questions and obtaining answers from other users. To enhance the responsiveness of such services, one can identify similar questions and, thereafter, return the answers available. However, identifying similar questions is difficult because of the complex language structure of user-generated questions. For this reason, we developed an approach to cluster similar questions based on a web of social relationships among the questions, the answers, the askers, and the answerers. To do so, we designed a graph-based cluster analysis using design science research guidelines. In evaluating the results, we found that the proposed graph-based cluster analysis is more promising than baseline methods.
Mixed UX Methods Can Help to Achieve Triumphs

Each user experience test is a unique. Researchers need to find out how to introduce the research target (e.g. application, device, service) to the participants and what methods to use for capturing one's subjective experiences. Each test participant is a unique. Researchers need to know how to handle each subject, how to get them to express their experiences, wishes and needs verbally or non-verbally. Mixed methods test procedures can help researchers to 1) introduce a test topic to participants step by step , and 2) learn about the users and their ways to express, and 3) catch user experience information piece by piece by utilizing different methods . This paper presents practical examples of different case studies, where several mixed methods have been used together for getting a deeper understanding of users' experiences.
A fast-acting reagent for accurate analysis of RNA secondary and tertiary structure by SHAPE chemistry.

Selective 2‘-hydroxyl acylation analyzed by primer extension (SHAPE) chemistry allows local nucleotide flexibility to be quantitatively assessed at single nucleotide resolution in any RNA. SHAPE chemistry exploits structure-based gating of the nucleophilic reactivity of the ribose 2‘-hydroxyl group by the extent to which a nucleotide is constrained or flexible. SHAPE chemistry was developed using N-methylisatoic anhydride (NMIA), which is only moderately electrophilic and requires tens of minutes to form ribose 2‘-O-adducts. Here, we design and evaluate a significantly more useful, fast-acting, reagent for SHAPE chemistry. Introduction of a nitro group para to the reactive carbonyl to form 1-methyl-7-nitroisatoic anhydride (1M7) yields a reagent that both reacts significantly more rapidly with RNA to form 2‘-O-adducts and is also more labile toward advantageous, self-limiting, hydrolysis. With 1M7, the single nucleotide resolution interrogation of the RNA structure is complete in 70 s. SHAPE analysis perf.
OSP: an environment for operating system projects

0S7) is both an implementation of a modern operating system, and a flexible environment for generating implementation projects appropriate for an introductory course in operating system design. It is intended to complement the use of most standard textbooks on operating systems and contains enough projects for up to three semesters. These projects expose students to many essential features of operating systems, while at the same time isolating them from low-level, machinedependent concerns. Thus, even in one semester, students can learn about page replacement strategies in virtual memory management, cpu scheduling strategies, disk seek time optimization, and other issues in operating system design.
Role of innate immunity in primary graft dysfunction after lung transplantation

Purpose of reviewPrimary graft dysfunction (PGD), a form of acute lung injury after lung transplantation, has a significant impact on clinical outcomes after lung transplantation. This potentially reversible graft impairment occurs after ischemia–reperfusion injury. This review describes the expanding body of literature evaluating the central role of innate immune activation, nonadaptive responses and dysregulation in the development of PGD after lung transplant. Recent findingsThe innate immune system, highlighted by Toll-like receptor pathways and neutrophil migration and influx, plays an important role in the initiation and propagation of ischemia–reperfusion injury. Recent plasma biomarker and gene association studies have identified several genes and proteins composing innate immune pathways to be associated with PGDs. Long pentraxin-3 and Toll-like receptors, as well as inflammasomes and Toll-interacting protein, are associated with the development of PGD after lung transplantation. SummaryInnate immune pathways are involved in the development of PGD and may provide attractive targets for therapies. It may be possible to prevent or treat PGD, as well as to allow pre-transplant PGD risk stratification. To improve understanding of the mechanisms behind clinical risk factors for PGD will require further in-depth correlation of donor-specific and recipient-related triggers of nonadaptive immune responses.
Preclinical and clinical studies of anticancer agent‐incorporating polymer micelles

The size of anticancer agent‐incorporating micelles can be controlled within the diameter range of 20–100 nm to ensure that they do not penetrate normal vessel walls. With this development, it is expected that the incidence of drug‐induced side‐effects may be decreased owing to the reduced drug distribution in normal tissue. Micelle systems can also evade non‐specific capture by the reticuloendothelial system because the outer shell of a micelle is covered with polyethylene glycol. Consequently, a polymer micelle carrier can be delivered selectively to a tumor by utilizing the enhanced permeability and retention effect. Moreover, a water‐insoluble drug can be incorporated into polymer micelles. Presently, several anticancer agent‐incorporating micelle carrier systems are under preclinical and clinical evaluation. Furthermore, nucleic acid‐incorporating micelle carrier systems are also being developed. (Cancer Sci 2009; 100: 572–579)
Function of the Basal Ganglia as Revealed by Cognitive and Motor Disorders in Parkinson’s Disease

ABSTRACT Early Parkinson’s disease is taken to be the best human model of disordered basal ganglia function. An experimental study in Parkinsonians with swings in motor response to drug treatment suggests that general cognition is not controlled by dopamine mediated striatal activity. The variety of motor disorders in Parkinson’s disease cannot be explained by simple concepts. Although Parkinsonians cannot execute fast ballistic movements, an experimental study shows that they can adopt a predictive motor control strategy. It is argued that simple motor programs are not grossly disturbed in Parkinson’s disease. It is concluded that Parkinsonians cannot automatically execute learned motor plans.
In Situ Generation of Compressed Inverted Files

An inverted index stores, for each term that appears in a collection of documents, a list of document numbers containing that term. Such an index is indispensable when Boolean or informal ranked queries are to be answered. Construction of the index is, however, a nontrivial task. Simple methods using in-memory data structures cannot be used for large collections because they require too much random access storage, and traditional disk-based methods require large amounts of temporary file space. This paper describes a new indexing algorithm designed to create large compressed inverted indexes in situ. It makes use of simple compression codes for the positive integers and an in-place external multi-way mergesort. The new technique has been used to invert a two-gigabyte text collection in under 4 hours, using less than 40 megabytes of temporary disk space, and less than 20 megabytes of main memory. © 1995 John Wiley & Sons, Inc.
Grassland gross carbon dioxide uptake based on an improved model tree ensemble approach considering human interventions: global estimation and covariation with climate

Grassland ecosystems act as a crucial role in the global carbon cycle and provide vital ecosystem services for many species. However, these low‐productivity and water‐limited ecosystems are sensitive and vulnerable to climate perturbations and human intervention, the latter of which is often not considered due to lack of spatial information regarding the grassland management. Here by the application of a model tree ensemble (MTE‐GRASS) trained on local eddy covariance data and using as predictors gridded climate and management intensity field (grazing and cutting), we first provide an estimate of global grassland gross primary production (GPP). GPP from our study compares well (modeling efficiency NSE = 0.85 spatial; NSE between 0.69 and 0.94 interannual) with that from flux measurement. Global grassland GPP was on average 11 ± 0.31 Pg C yr−1 and exhibited significantly increasing trend at both annual and seasonal scales, with an annual increase of 0.023 Pg C (0.2%) from 1982 to 2011. Meanwhile, we found that at both annual and seasonal scale, the trend (except for northern summer) and interannual variability of the GPP are primarily driven by arid/semiarid ecosystems, the latter of which is due to the larger variation in precipitation. Grasslands in arid/semiarid regions have a stronger (33 g C m−2 yr−1/100 mm) and faster (0‐ to 1‐month time lag) response to precipitation than those in other regions. Although globally spatial gradients (71%) and interannual changes (51%) in GPP were mainly driven by precipitation, where most regions with arid/semiarid climate zone, temperature and radiation together shared half of GPP variability, which is mainly distributed in the high‐latitude or cold regions. Our findings and the results of other studies suggest the overwhelming importance of arid/semiarid regions as a control on grassland ecosystems carbon cycle. Similarly, under the projected future climate change, grassland ecosystems in these regions will be potentially greatly influenced.
Degradation of phenol by Pseudomonas putida ATCC 11172 in continuous culture at different ratios of biofilm surface to culture volume

Pseudomonas putida ATCC 11172 was grown in continuous culture with phenol as the only carbon and energy source; a culture practically without biofilm was compared with biofilm cultures of differing surface area/volume ratios. The biofilm did not significantly affect the maximal suspended cell concentration in the effluent, but it increased the maximal phenol reduction rate from 0.23 g/liter per h (without biofilm) to 0.72 g/liter per h at the highest biofilm level (5.5 cm2 of biofilm surface per ml of reactor volume). The increase in phenol reduction rate was linear up to the surface area/volume ratio of 1.4 cm2/ml. The continuous cultures with biofilms could tolerate a higher phenol concentration of the medium (3.0 g/liter) than the nonbiofilm system (2.5 g/liter). At higher dilution rates an intermediate product, 2-hydroxymuconic semialdehyde, accumulated in the culture. When the biomass of the effluent started to decrease, the concentration of 2-hydroxymuconic semialdehyde reached a peak value. We conclude that biofilms in continuous culture have the potential to enhance the aerobic degradation of aromatic compounds.
Nonuniform Frequency Diverse Array for Range-Angle Imaging of Targets

Although phased-array antennas are widely used in communication, radar, and navigation systems, its beampattern is a function of angle only and thus there is no range information. To circumvent this limitation, we design a frequency diverse array (FDA) antenna system for range-angle imaging of targets. Our approach exploits the nonuniform FDA as the transmitter to provide range-dependent beampattern and the uniform phased-array as the receiver which results in angle-dependent beampattern. Range-angle imaging of targets is achieved from the cooperative transmit-receive beamforming. The imaging performance measures including spatial resolution and system processing gain are analyzed. In addition, several design specifications are discussed. The effectiveness of the proposed approach is verified by simulation results.
A Sufficient Statistics Approach for Aggregating Firm-Level Experiments

We consider a dynamic economy populated by heterogeneous firms subject to generic capital frictions: adjustment costs, taxes and financing constraints. A random subset of firms in this economy receives an empirical "treatment", which modifies the parameters governing these frictions. An econometrician observes the firm-level response to this treatment, and wishes to calculate how macroeconomic outcomes would change if all firms in the economy were treated. Our paper proposes a simple methodology to estimate this aggregate counterfactual using firm-level evidence only. Our approach takes general equilibrium effects into account, requires neither a structural estimation nor a precise knowledge on the exact nature of the experiment and can be implemented using simple moments of the distribution of revenue-to-capital ratios. We provide a set of sufficient conditions under which these formulas are valid and investigate the robustness of our approach to multiple variations in the aggregation framework.
Inferring global perceptual contours from local features

An attempt is made to solve the problem of imperfect data produced by state-of-the-art edge detectors through the implementation of laws of perceptual grouping, derived from psychology. A saliency-enhancing operator is introduced. It is capable of highlighting features (edges, junctions, etc.) which are considered important psychologically. It also infers features which are not detected by low-level detectors. It is shown how to extract salient curves and junctions and generate a description ranking these features by the likelihood of them occurring accidentally. The problem of illusory contours apparent in end-point formations is discussed. All operations are parameter-free, noniterative and are linear with the number of edges in the input image. <<ETX>>
Development of Impurity Profiling Methods Using Modern Analytical Techniques

ABSTRACT This review gives a brief introduction about the process- and product-related impurities and emphasizes on the development of novel analytical methods for their determination. It describes the application of modern analytical techniques, particularly the ultra-performance liquid chromatography (UPLC), liquid chromatography-mass spectrometry (LC-MS), high-resolution mass spectrometry (HRMS), gas chromatography-mass spectrometry (GC-MS) and high-performance thin layer chromatography (HPTLC). In addition to that, the application of nuclear magnetic resonance (NMR) spectroscopy was also discussed for the characterization of impurities and degradation products. The significance of the quality, efficacy and safety of drug substances/products, including the source of impurities, kinds of impurities, adverse effects by the presence of impurities, quality control of impurities, necessity for the development of impurity profiling methods, identification of impurities and regulatory aspects has been discussed. Other important aspects that have been discussed are forced degradation studies and the development of stability indicating assay methods.
EFFECT OF DIETARY PROBIOTICS SUPPLEMENTATION WITH DIFFERENT NUTRIENT DENSITY ON GROWTH PERFORMANCE, NUTRIENT RETENTION AND DIGESTIVE ENZYME ACTIVITIES IN BROILERS

This study was involving a 2×2 factorial arrangement (2 nutrient density diets with 2 levels of probiotics), to evalua te effect of probiotics on growth performance, nutrient retention and digestive enzyme activities of broilers. Three hundred and twenty one-day-old chickens were randomly divided into four groups with 10 replicate of 8 broilers each for a 42 -d feeding trial.The dietary were formulated: a positive control diet (PC) and a negative control diet (NC) to contain 320 KJ metabolizable energy /kg diet and 0.85 percentage crude protein less than PC, which both were supplemented with0 or 100 mg/kg probiotics. Broilers fed NC diet tended to reduce body weightˇ� BW and average daily gain (ADG) (P=0.063) in starter phase (1 -21 d). Probiotics treatments improved 21-d BW, ADG (P<0.05) and feed/gain ratio (P=0.078) in starter phase. Probiotics improved the retention of CP (P<0.05) during 11-14 d, but reduced the activity of lipase in pancreas of broilers ( P<0.01) at 21 d. It was concluded that low nutrient density tended to reduce BW and ADG of broilers in starter phase, but probiotics improved the starter phase of growth perfo rmance and retention of CP, reduced pancreatic lipase activity of broilers.
Correlates of the Tourniquet Ischemia Pain Ratio

The Tourniquet Ischemia Pain Ratio was developed as a measure of pain. The present study examined the relationship between the ratio and other measures thought to be relevant to a patient's perception of, and reaction to, chtonic pain. The ratio was correlated with the patient's estimate of the pain, the perceived impact of the pain on daily life, the degree of reactive depression, and a measure of hypochondriasis. The ratio relates to both pain and hypochondriacal tendencies.
A Qualitative Study to Develop a Tool to Examine Patients’ Perceptions of NHS Orthodontic Treatment

Objective To identify issues of importance to adolescent patients surrounding the delivery of orthodontic treatment under the National Health Service (NHS), which can form the basis of a tool to examine patients’ perceptions of NHS orthodontic treatment. Design Study using qualitative research methods. Setting Patients were recruited from the orthodontic departments at Derriford Hospital and Bristol Dental Hospital, and from Specialist Orthodontic Practices in Plymouth and Solihull. Subjects A rolling sample of patients from a list of orthodontic patients under treatment at each site was selected. Twenty-six patients took part in five focus group meetings. Three patients took part in semi-structured telephone interviews. Methods Participants were invited to participate in either a focus group meeting or a telephone interview. The transcripts of these meetings were analysed by two researchers working independently. Issues of importance to patients regarding the delivery of orthodontic treatment under the NHS were identified. Results The issues identified included being treated with respect by the clinician and being included in discussions about treatment. Participants tended to rely on their peers for advice about what to expect from treatment. The patients also discussed the benefits to them of undergoing orthodontic treatment. These included an improved appearance and increased self-confidence. Conclusion This qualitative research has identified issues that are important to adolescent orthodontic patients. These issues will be used to form the basis of a patient-centred measure for auditing patients’ perceptions of orthodontic treatment under the NHS.
Inflammation and insulin resistance induced by trans-10, cis-12 conjugated linoleic acid depend on intracellular calcium levels in primary cultures of human adipocytes

We previously demonstrated that trans-10, cis-12 (10,12) conjugated linoleic acid (CLA) induced inflammation and insulin resistance in primary human adipocytes by activating nuclear factor κB (NFκB) and extracellular signal-related kinase (ERK) signaling. In this study, we demonstrated that the initial increase in intracellular calcium ([Ca2+]i) mediated by 10,12 CLA was attenuated by TMB-8, an inhibitor of calcium release from the endoplasmic reticulum (ER), by BAPTA, an intracellular calcium chelator, and by D609, a phospholipase C (PLC) inhibitor. Moreover, BAPTA, TMB-8, and D609 attenuated 10,12 CLA–mediated production of reactive oxygen species (ROS), activation of ERK1/2 and cJun-NH2-terminal kinase (JNK), and induction of inflammatory genes. 10,12 CLA–mediated binding of NFκB to the promoters of interleukin (IL)-8 and cyclooxygenase (COX)-2 and induction of calcium-calmodulin kinase II (CaMKII) β were attenuated by TMB-8. KN-62, a CaMKII inhibitor, also suppressed 10,12 CLA–mediated ROS production and ERK1/2 and JNK activation. Additionally, KN-62 attenuated 10,12 CLA induction of inflammatory and integrated stress response genes, increase in prostaglandin F2α, and suppression of peroxisome proliferator activated receptor γ protein levels and insulin-stimulated glucose uptake. These data suggest that 10,12 CLA increases inflammation and insulin resistance in human adipocytes, in part by increasing [Ca2+]i levels, particularly calcium from the ER.