Miracle-dz/UniFAR-FTUs huggingface dataset:
Recent advances using zebrafish animal models for muscle disease drug discovery

Introduction: Animal models have enabled great progress in the discovery and understanding of pharmacological approaches for treating muscle diseases like Duchenne muscular dystrophy. Areas covered: With this article, the author provides the reader with a description of the zebrafish animal model, which has been employed to identify and study pharmacological approaches to muscle disease. In particular, the author focuses on how both large-scale chemical screens and targeted drug treatment studies have established zebrafish as an important model for muscle disease drug discovery. Expert opinion: There are a number of opportunities arising for the use of zebrafish models for further developing pharmacological approaches to muscle diseases, including studying drug combination therapies and utilizing genome editing to engineer zebrafish muscle disease models. It is the author’s particular belief that the availability of a wide range of zebrafish transgenic strains for labeling immune cell types, combined with live imaging and drug treatment of muscle disease models, should allow for new elegant studies demonstrating how pharmacological approaches might influence inflammation and the immune response in muscle disease.
Automatic discovery of mutual exclusion algorithms

We present a methodology for automatic discovery of synchronization algorithms. We built a tool and used it to automatically discover hundreds of new algorithms for the well-known problem of mutual exclusion. The methodology is rather simple and the fact that it is computationally feasible is surprising. Our brute force approach may require (even for short algorithms) the mechanical verification of hundreds of millions of incorrect algorithms before a correct algorithm is found. Although many new interesting algorithms have been found, we think the main contribution of this work is in demonstrating that the approach suggested for automatic discovery of (correct) synchronization algorithms is feasible.
OPTIMAL SELECTION OF ENZYME LEVELS USING LARGE-SCALE KINETIC MODELS

Abstract A hybrid optimization framework is introduced to identify enzyme sets and levels to meet overproduction requirements using kinetic models of metabolism. A simulated annealing algorithm is employed to navigate through the discrete space of enzyme sets while a sequential quadratic programming method is utilized to identify optimal enzyme levels. The framework is demonstrated on a model of E.coli central metabolism for serine biosynthesis. Computational results show that by optimally manipulating relatively small enzyme sets, a substantial increase in serine production can be achieved. The proposed approach thus provides a versatile tool for the elucidation of controlling enzymes with implications in biotechnology.
Dry needle stimulation of myofascial trigger points evokes segmental anti-nociceptive effects.

OBJECTIVE To test the hypothesis that dry needle stimulation of a myofascial trigger point (sensitive locus) evokes segmental anti-nociceptive effects. DESIGN Double-blind randomized controlled trial. SUBJECTS Forty subjects (21 males, 19 females). METHODS Test subjects received intramuscular dry needle puncture to a right supraspinatus trigger point (C4,5); controls received sham intramuscular dry needle puncture. Pain pressure threshold (PPT) readings were recorded from right infraspinatus (C5,6) and right gluteus medius (L4,5S1) trigger points at 0 (pre-needling baseline), 1, 3, 5, 10 and 15 min post-needling and normalized to baseline values. The supraspinatus and infraspinatus trigger points are neurologically linked at C5; the supraspinatus and gluteus medius are segmentally unrelated. The difference between the infraspinatus and gluteus medius PPT values (PPTseg) represents a direct measure of the segmental anti-nociceptive effects acting at the infraspinatus trigger point. RESULTS Significant increases in PPTseg were observed in test subjects at 3 (p = 0.002) and 5 (p = 0.015) min post-needling, compared with controls. CONCLUSION One intervention of dry needle stimulation to a single trigger point (sensitive locus) evokes short-term segmental anti-nociceptive effects. These results suggest that trigger point (sensitive locus) stimulation may evoke anti-nociceptive effects by modulating segmental mechanisms, which may be an important consideration in the management of myofascial pain.
Revenue Management in Order-Driven Production Systems

This article investigates the effectiveness of a tactical demand-capacity management policy to guide operational decisions in order-driven production systems. The policy is implemented via a heuristic that attempts to maximize revenue by selectively accepting or rejecting customer orders for multiple product classes when demand exceeds capacity constantly over the short term. The performance of the heuristic is evaluated in terms of its ability to generate a higher profit compared to a first-come-first-served (FCFS) policy. The policies are compared over a wide range of conditions characterized by variations in both internal (firm) and external (market) factors. The heuristic, when used with a Whole Lot order-processing approach, produces higher profit compared to FCFS when profit margins of products are substantially different from each other and demand exceeds capacity by a large amount. In other cases it is better to use the heuristic in conjunction with the Split Lot order-processing approach.
Global alignment of multiple protein interaction networks with application to functional orthology detection

Protein–protein interactions (PPIs) and their networks play a central role in all biological processes. Akin to the complete sequencing of genomes and their comparative analysis, complete descriptions of interactomes and their comparative analysis is fundamental to a deeper understanding of biological processes. A first step in such an analysis is to align two or more PPI networks. Here, we introduce an algorithm, IsoRank, for global alignment of multiple PPI networks. The guiding intuition here is that a protein in one PPI network is a good match for a protein in another network if their respective sequences and neighborhood topologies are a good match. We encode this intuition as an eigenvalue problem in a manner analogous to Google's PageRank method. Using IsoRank, we compute a global alignment of the Saccharomyces cerevisiae, Drosophila melanogaster, Caenorhabditis elegans, Mus musculus, and Homo sapiens PPI networks. We demonstrate that incorporating PPI data in ortholog prediction results in improvements over existing sequence-only approaches and over predictions from local alignments of the yeast and fly networks. Previous methods have been effective at identifying conserved, localized network patterns across pairs of networks. This work takes the further step of performing a global alignment of multiple PPI networks. It simultaneously uses sequence similarity and network data and, unlike previous approaches, explicitly models the tradeoff inherent in combining them. We expect IsoRank—with its simultaneous handling of node similarity and network similarity—to be applicable across many scientific domains.
Seeing is understanding: anomaly detection in blockchains with visualized features

Modern IoT solutions are often an intricate system of interdependent components. Traditional monitoring techniques may not be sufficient to ensure the correct operation of those systems. We present an on-line machine learning approach for anomaly detection that is optimized for interpretability. The aim is to make it as intuitive as possible for human operators to derive insights about the system. To this end we combine characteristics of the system into sets of features that can be rendered graphically. Our solution builds on open source components and applies to any time series of numerical data. This work originated within a larger project on connected mobility that uses Blockchain technology to guarantee data integrity. Hence we demonstrate some results at the example of the public Ethereum blockchain. Further work will extend the solution to more general sensor data from the IoT realm.
Enrichment and Purification of Syringin, Eleutheroside E and Isofraxidin from Acanthopanax senticosus by Macroporous Resin

In order to screen a suitable resin for the preparative simultaneous separation and purification of syringin, eleutheroside E and isofraxidin from Acanthopanax senticosus, the adsorption and desorption properties of 17 widely used commercial macroporous resins were evaluated. According to our results, HPD100C, which adsorbs by the molecular tiers model, was the best macroporous resin, offering higher adsorption and desorption capacities and higher adsorption speed for syringin, eleutheroside E and isofraxidin than other resins. Dynamic adsorption and desorption tests were carried out to optimize the process parameters. The optimal conditions were as follows: for adsorption, processing volume: 24 BV, flow rate: 2 BV/h; for desorption, ethanol–water solution: 60:40 (v/v), eluent volume: 4 BV, flow rate: 3 BV/h. Under the above conditions, the contents of syringin, eleutheroside E and isofraxidin increased 174-fold, 20-fold and 5-fold and their recoveries were 80.93%, 93.97% and 93.79%, respectively.
Biological Properties of Iron Oxide Nanoparticles for Cellular and Molecular Magnetic Resonance Imaging

Superparamagnetic iron-oxide particles (SPIO) are used in different ways as contrast agents for magnetic resonance imaging (MRI): Particles with high nonspecific uptake are required for unspecific labeling of phagocytic cells whereas those that target specific molecules need to have very low unspecific cellular uptake. We compared iron-oxide particles with different core materials (magnetite, maghemite), different coatings (none, dextran, carboxydextran, polystyrene) and different hydrodynamic diameters (20–850 nm) for internalization kinetics, release of internalized particles, toxicity, localization of particles and ability to generate contrast in MRI. Particle uptake was investigated with U118 glioma cells und human umbilical vein endothelial cells (HUVEC), which exhibit different phagocytic properties. In both cell types, the contrast agents Resovist, B102, non-coated Fe3O4 particles and microspheres were better internalized than dextran-coated Nanomag particles. SPIO uptake into the cells increased with particle/iron concentrations. Maximum intracellular accumulation of iron particles was observed between 24 h to 36 h of exposure. Most particles were retained in the cells for at least two weeks, were deeply internalized, and only few remained adsorbed at the cell surface. Internalized particles clustered in the cytosol of the cells. Furthermore, all particles showed a low toxicity. By MRI, monolayers consisting of 5000 Resovist-labeled cells could easily be visualized. Thus, for unspecific cell labeling, Resovist and microspheres show the highest potential, whereas Nanomag particles are promising contrast agents for target-specific labeling.
An Experimental Study of the Effects of Class Size

The study investigated the effects of four class sizes (16, 23, 30, and 37) on teachers’ expectations; the attitudes and opinions of participants (students and teachers); student achievement in reading, mathematics, composition, and art; student self-concept; and a variety of classroom process variables (e.g., teacher-pupil interaction, pupil participation, method of instruction). Teachers and students were randomly assigned to a class size in Grades 4 and 5. A total of 62 classes in three school districts in Metropolitan Toronto participated in the two-year study. Findings indicated that teachers had definite expectations of class size effects that subsequently were reported to be confirmed by their experience in the study. However, most other results failed to support teachers’ opinions. Few of the observed classroom process variables were affected by class size. Although students’ mathematics-concept scores were higher in size 16 than 30 or 37, there were no class size effects for the other achievement measures (reading, vocabulary, mathematics-problem solving, art, and composition) or for students’ attitudes and self-concepts.
2.8 Å resolution reconstruction of the Thermoplasma acidophilum 20S proteasome using cryo-electron microscopy

Recent developments in detector hardware and image-processing software have revolutionized single particle cryo-electron microscopy (cryoEM) and led to a wave of near-atomic resolution (typically ∼3.3 Å) reconstructions. Reaching resolutions higher than 3 Å is a prerequisite for structure-based drug design and for cryoEM to become widely interesting to pharmaceutical industries. We report here the structure of the 700 kDa Thermoplasma acidophilum 20S proteasome (T20S), determined at 2.8 Å resolution by single-particle cryoEM. The quality of the reconstruction enables identifying the rotameric conformation adopted by some amino-acid side chains (rotamers) and resolving ordered water molecules, in agreement with the expectations for crystal structures at similar resolutions. The results described in this manuscript demonstrate that single particle cryoEM is capable of competing with X-ray crystallography for determination of protein structures of suitable quality for rational drug design. DOI: http://dx.doi. org/10.7554/eLife.06380. 001
Multi-agent control algorithms for chemical cloud detection and mapping using unmanned air vehicles

Traditional control approaches fall well short of the necessary flexibility and efficiency needed to meet the commercial and military demands placed upon UAV swarms. Effective coordination of these swarms requires development of control strategies based on emergent behavior. We have developed a rule-based, decentralized control algorithm that relies on constrained randomized behavior and respects UAV restrictions on sensors, computation, and flight envelope. To demonstrate and evaluate the effectiveness of our approach, we have created a simulation of an air vehicle swarm searching for and mapping a chemical cloud within a patrolled region. We then consider several different detection and mapping strategies based on emergent behavior. We then establish an inverse linear relation between the size of the swarm and the time to detect the cloud, regardless of the size of the cloud. Further, we also show the size of the swarm has a linear relation with the successful detection of the cloud.
Tomlinson Harashima Precoding Design for Non-Regenerative MIMO Relay Networks

In this paper we consider the design of minimum mean square error (MMSE) transceivers for non-regenerative multiple input multiple output (MIMO) relay systems. Our design utilises Tomlinson Harashima precoding (THP) at the source along with linear processors in each stage of the network. Assuming full channel state information (CSI) is available at each node in the network the various processors are jointly optimised to minimise the system arithmetic mean square error (MSE) whilst abiding by average power constraints at both the source and relay terminals in the network. Simulations show that the proposed schemes outperform existing methods in terms of bit error ratio (BER).
Fibre diffraction of hair can provide a screening test for Alzheimer's disease: a human and animal model study.

BACKGROUND Studies of molecular changes in hair as possible biomarkers for specific cancers revealed an additional molecular change in the diffraction patterns of some persons aged over 75. This change was found to correlate with the presence of Alzheimer's disease (AD). To confirm this correlation and its relation to the presence of a human APP mutation, known to definitely cause AD, hairs were examined from AD patients, pregnant women known to have an increase in plasma beta amyloid and transgenic mice carrying a mutated human APP gene. Patients were clinically examined by an experienced physician who recorded the patient's history and completed physical and neurological examinations. Hair samples were held taut and centred in the beam. The diffraction patterns were collected on Fuji-Bas Imaging plates and analysed using standard programs. MATERIAL/METHODS A fan-shaped set of spot-like reflections was observed in the equatorial diffraction patterns from the hair of all AD patients and all third trimester pregnant women. Combined fibre diffraction of hair and histopathologic examination of brains from transgenic mice carrying a mutated human APP gene confirmed that these changes are related to the mutated human APP genes and the formation of beta amyloid plaques. RESULTS Here we show results that fibre diffraction analysis would provide a non-invasive, accurate bio-marker for Alzheimer's disease. Our results are consistent with the hypothesis that this marker is related to the presence of mutated human APP genes and indicate that the structural change precedes the significant development of plaques. CONCLUSIONS Here we show results that fibre diffraction analysis would provide a non-invasive, accurate bio-marker for Alzheimer's disease. Our results are consistent with the hypothesis that this marker is related to the presence of mutated human APP genes and indicate that the structural change precedes the significant development of plaques.
Outcomes of Extra-articular, Intra-epiphyseal Drilling for Osteochondritis Dissecans of the Knee

Background When conservative management fails to heal femoral condyle osteochondritis dissecans (OCD) lesions in a child, then drilling of the subchondral plate below the lesion to stimulate healing may be beneficial. This study reviews the outcomes of extra-articular, intraepiphyseal drilling of OCD lesions of the knee with intact articular cartilage. Methods Over an 8-year period, all children, who failed at least 6 months of nonoperative management, underwent arthroscopic knee surgery and extra-articular, intra-epiphyseal drilling for their symptomatic, nondisplaced femoral condyle OCD lesions. The clinical and radiographic outcomes were evaluated by using demographics, preoperative size of the lesion, intraoperative concomitant pathology, complications, postoperative range of motion, return to activities, radiographic progression of healing, and subsequent operative procedures. Results In all 59 children, the mean time to return to activities was 2.8 months (1.3 to 13.1 mo) and the mean percentage of radiographic healing was 98.2% (79% to 100%) at final follow-up. Forty-four (75%) of the OCD lesions were successfully treated to 100% radiographic healing with an average time for healing of 11.9 months (1.3 to 47.3 mo). The large lesions took significantly longer to heal than the small lesions, 15.3 months versus 8.8 months (P=0.032), and the percentage of radiographic healing at final follow-up approached significance with large (>3.2 cm2) lesions attaining a mean of 96.9% (standard deviation 6.4%) versus small lesions (<3.2 cm2) with a mean of 99.4% (standard deviation 2.1%, P=0.083). No operative complications were observed. Conclusions Extra-articular, intraepiphyseal drilling of OCD lesions produced excellent results over the historical controls using intra-articular drilling for those patients who failed initial conservative management. This technique allows for more drill holes to be placed perpendicular to the OCD lesions, especially the posterior lesions that may have limited intra-articular access. Furthermore, this technique avoids intraoperative damage to the overlying intact articular cartilage and promotes osseous healing by fenestration of the sclerotic rim surrounding the OCD lesion. Level of Incidence Prognostic study, Level IV (retrospective study).
Spontaneous Hemorrhagic Stroke in a Mouse Model of Cerebral Amyloid Angiopathy

A high risk factor for spontaneous and often fatal lobar hemorrhage is cerebral amyloid angiopathy (CAA). We now report that CAA in an amyloid precursor protein transgenic mouse model (APP23 mice) leads to a loss of vascular smooth muscle cells, aneurysmal vasodilatation, and in rare cases, vessel obliteration and severe vasculitis. This weakening of the vessel wall is followed by rupture and bleedings that range from multiple, recurrent microhemorrhages to large hematomas. Our results demonstrate that, in APP transgenic mice, the extracellular deposition of neuron-derived β-amyloid in the vessel wall is the cause of vessel wall disruption, which eventually leads to parenchymal hemorrhage. This first mouse model of CAA-associated hemorrhagic stroke will now allow development of diagnostic and therapeutic strategies.
The Institutional Environment for Economic Growth

This article forges an explicit link between an objective measure of political constraints and variation in cross-national growth rates. It derives a new measure of political constraints from a simple spatial model of political interaction that incorporates information on the number of independent branches of government with veto power and the distribution of preferences across and within those branches. The derived variable is found to have a statistically and economically significant impact on growth rates using simple ordinary least squares, three-stage least squares and generalized method of moments estimation techniques. Copyright 2000 Blackwell Publishers Ltd.
“Nil per oral after midnight”: Is it necessary for clear fluids?

Fasting before general anaesthesia aims to reduce the volume and acidity of stomach contents, thus reducing the risk of regurgitation and aspiration. Recent guidelines have recommended a shift in fasting policies from the standard ‘nil per oral from midnight’ to a more relaxed policy of clear fluid intake a few hours before surgery. The effect of preoperative oral administration of 150 ml of water 2 h prior to surgery was studied prospectively in 100 ASA I and II patients, for elective surgery. Patients were randomly assigned to two groups. Group I (n = 50) was fasting overnight while Group II (n = 50) was given 150 ml of water 2 h prior to surgery. A nasogastric tube was inserted after intubation and gastric aspirate was collected for volume and pH. The gastric fluid volume was found to be lesser in Group II (5.5 ± 3.70 ml) than Group I (17.1 ± 8.2 ml) which was statistically significant. The mean pH values for both groups were similar. Hence, we conclude that patients not at risk for aspiration can be allowed to ingest 150 ml water 2 h prior to surgery.
Simulation-equation-based methodology for design of CMOS amplifiers using Geometric Programming

Geometric programming (GP) has been employed in automatic design of analog integrated circuits. Its major advantage is the ability to find the globally optimum solution to a problem. It however, suffers from dependency on the accuracy of the initial equations and the parameters used in these equations. This, in circuit design, causes discrepancies between GP predictions and simulation results-especially in sub-micron devices-thus resulting in a non-globally optimum circuit design. In this paper, two major sources of this discrepancy are introduced and resolved by an iterative simulation-equation-based design methodology based on GP for operational amplifiers. In order to show the effectiveness of the methodology, it has been applied to two op-amp architectures.