Miracle-dz/UniFAR-FTUs huggingface dataset:
Exploring the Dual Inhibitory Activity of Novel Anthranilic Acid Derivatives towards α-Glucosidase and Glycogen Phosphorylase Antidiabetic Targets: Design, In Vitro Enzyme Assay, and Docking Studies

A few new anthranilate diamide derivatives, 3a–e, 5a–c and 7a–d, were designed, synthesized, and evaluated for their inhibitory activity against two interesting antidiabetic targets, α-glucosidase and glycogen phosphorylase enzymes. Different instrumental analytical tools were applied in identification and conformation of their structures like; 13C NMR, 1H NMR and elemental analysis. The screening of the novel compounds showed potent inhibitory activity with nanomolar concentration values. The most active compounds (5c) and (7b) showed the highest inhibitory activity against α-glucosidase and glycogen phosphorylase enzymes IC50 = 0.01247 ± 0.01 µM and IC50 = 0.01372 ± 0.03 µM, respectively. In addition, in vivo testing of the highly potent α-glucosidase inhibitor (7b) on rats with DTZ-induced diabetes was done and showed significant reduction of blood glucose levels compared to the reference drug. Furthermore, a molecular docking study was performed to help understand the binding interactions of the most active analogs with these two enzymes. The data obtained from the molecular modeling were correlated with those obtained from the biological screening. These data showed considerable antidiabetic activity for these newly synthesized compounds.
Quiescent state and outburst evolution of SGR 0501+4516

This work was supported by the grants AYA2012-39303, SGR2009-811, and iLINK2011-0303. AP is supported by a Juan de la Cierva Fellowship in IEEC. NR is supported by a Ramon y Cajal fellowship and by an NWO Vidi Award. DV was supported by the grants AYA2010-21097-C03-02, ACOMP/2012/135, AYA 2012-39303 and SGR 2009-811.
Effects of Exercise Training Combined with Increased Physical Activity to Prevent Chronic Pain in Community-Dwelling Older Adults: A Preliminary Randomized Controlled Trial

Objective With the aim of developing a chronic pain prevention program, this randomized controlled trial examined whether exercise training combined with increased physical activity more effectively improves pain and physical activity than exercise training alone in community-dwelling older adults without chronic pain. Methods We randomized 76 older adults without chronic pain into an intervention group (n=38) involving exercise training combined with increased physical activity and a control group (n=38) involving exercise training alone. The exercise training comprised weekly 60-min sessions for 12 weeks. The program to increase physical activity required participants to record their daily step counts using pedometers. Pain intensity, total number of pain sites, and physical activity were assessed before and 12 weeks after the intervention. Results A time-by-group interaction was found for physical activity, with the intervention group showing significant improvement (p < 0.05). The intervention group also showed greater improvement in pain intensity and total number of pain sites at 12 weeks after intervention than the control group (p < 0.05). Conclusions In older adults without chronic pain, exercise training combind with increased physical activity improves key outcome indicators more effectively than exercise training alone. “This trial is registered with UMIN000018503. ”
Klebsiella pneumoniae SnebYK Mediates Resistance Against Heterodera glycines and Promotes Soybean Growth

Soybean is an important economic crop that is often adversely affected by infection in the field with the soybean cyst nematode Heterodera glycines. Biological control is an eco-friendly method used to protect the crop against disease. The bacterium Klebsiella pneumoniae has been reported to protect rice from sheath blight and seedling blight, but its role in the control of nematode is unclear. In this study, the effect of K. pneumoniae SnebYK on the control of H. glycines was assessed. Potting experiment results showed that coating soybean seeds with K. pneumoniae SnebYK not only reduced the infection rate of H. glycines but also decreased the proportion of adult female nematodes. Field experiment results showed that K. pneumoniae SnebYK reduced both the number of H. glycines in soybean roots and the number of adult females. However, K. pneumoniae SnebYK caused low juvenile mortality in an in vitro assay. To further analyze the role of K. pneumoniae SnebYK in the inhibition of H. glycines infection, split root experiments were conducted. The results indicated that K. pneumoniae SnebYK controls H. glycines via induced systemic resistance, which reduces H. glycines penetration. Klebsiella pneumoniae SnebYK treatment also significantly increased the proportion of second-stage juveniles and decreased the proportions of third- and fourth-stage juveniles in the H. glycines population. Moreover, 48 h after inoculation with H. glycines, the expression levels of PR1, PR2, PR5, and PDF1.2 were significantly higher in soybeans pretreated with K. pneumoniae SnebYK than in control soybeans. Interestingly, besides providing protection against nematodes, K. pneumoniae SnebYK fixed nitrogen, produced ammonia, solubilized phosphate, and produced siderophores, leading to well-developed root system and an increase in soybean seedling fresh weight. These results demonstrate for the first time that K. pneumoniae SnebYK not only promotes soybean growth but also inhibits the invasion and development of H. glycines by inducing systemic resistance.
Characterizing the Learning Effect in Response to Biofeedback Aimed at Reducing Tibial Acceleration during Running

Increased tibial acceleration has been found to be an important risk factor for tibial stress fractures. Interventions aimed at reducing this variable which found a beneficial effect include the use of biofeedback in gait retraining. However, no studies have focused on the time participants take to modify tibial acceleration, therefore we aimed to find the start of a learning plateau in this study. Six participants ran on a treadmill while multisensory feedback was given. A single-subject analysis was used to characterise the learning effects. All participants changed peak tibial acceleration within the first step of running in the feedback condition. Two participants further reduced tibial acceleration to reach a plateau within 120 steps. In four of the six participants a strong effect of the feedback was still present after a week. Further research is needed to optimise the use of biofeedback in reducing the prevalence of tibial stress fractures.
Towards the systematic development of hybrid software development processes

Hybrid approaches for software and system development have become reality. Recent research shows the use of hybrid development approaches mainly grounded in experience and driven by pragmatism. At the same time, a vast number of success factors is known that influences process development and process use alike. However, even though industrial practice shows a need for hybrid development approaches and knowledge regarding the success factors is in place, a systematic approach to develop, deploy and tailor hybrid development approaches is missing. This paper reports on ongoing research that aims at developing a method to support the evidence-driven construction of hybrid development approaches. We provide an overview of the required method components and outline how hybrid development approaches can be deployed at the organizational level and tailored at the project level. We further give an overview of ongoing and completed studies supporting the method's construction and evaluation.
OntoElecting Requirements for Domain Ontologies The Case of Time Domain

This paper reports on the use of the OntoElect methodology for evaluating the fitness of an existing ontology to the requirements of the knowledge stakeholders in a domain. It demonstrates, that a thorough routine for indirect elicitation, ensuring completeness, correctness of interpretation, using in ontology evaluation of these requirements is a must for ontology engineering. This is also valid if the requirements for ontology refinement are elaborated by a very high profile expert working groups. The approach used in the reported research is based on the use of OntoElect – the methodology for ontology refinement. The workflow of OntoElect contains three phases: feature elicitation, requirements conceptualization, and ontology evaluation. It elicits the set of terms extracted from a saturated collection of documents in the domain. It further sublimates these terms to the set of required features using the information about term significance in the form of numeric scores. Furthermore, it applies conceptualization and formalization activities to these features yielding their aggregations as ontological fragments interpreted as formalized requirements. Finally, the mappings are specified between the elements in the requirements and ontology elements. The scores are used in the mappings to indicate the strength of positive or negative votes regarding the evaluated ontology. The sum of the votes gives the overall numeric fitness measure of the ontology to the domain requirements. The paper presents the use of OntoElect in the use case of evaluating the W3C OWL-Time ontology against the requirements extracted from the proceedings of the TIME symposia series.
In Silico Characterization and Structural Modeling of Dermacentor andersoni p36 Immunosuppressive Protein

Ticks cause approximately $17–19 billion economic losses to the livestock industry globally. Development of recombinant antitick vaccine is greatly hindered by insufficient knowledge and understanding of proteins expressed by ticks. Ticks secrete immunosuppressant proteins that modulate the host's immune system during blood feeding; these molecules could be a target for antivector vaccine development. Recombinant p36, a 36 kDa immunosuppressor from the saliva of female Dermacentor andersoni, suppresses T-lymphocytes proliferation in vitro. To identify potential unique structural and dynamic properties responsible for the immunosuppressive function of p36 proteins, this study utilized bioinformatic tool to characterize and model structure of D. andersoni p36 protein. Evaluation of p36 protein family as suitable vaccine antigens predicted a p36 homolog in Rhipicephalus appendiculatus, the tick vector of East Coast fever, with an antigenicity score of 0.7701 that compares well with that of Bm86 (0.7681), the protein antigen that constitute commercial tick vaccine Tickgard™. Ab initio modeling of the D. andersoni p36 protein yielded a 3D structure that predicted conserved antigenic region, which has potential of binding immunomodulating ligands including glycerol and lactose, found located within exposed loop, suggesting a likely role in immunosuppressive function of tick p36 proteins. Laboratory confirmation of these preliminary results is necessary in future studies.
Age- and Gender-Based Differences in Nest-Building Behavior and Learning and Memory Performance Measured Using a Radial Six-Armed Water Maze in C57BL/6 Mice

Background Understanding age-based and gender-based behavioral changes is becoming more important as a greater percentage of people lives longer worldwide. In this study, a C57BL/6 mouse animal model was used to study age-based and gender-based behavioral differences using nest building and radial six-armed water maze (RAWM) testing. Methods In C57BL/6 mice, nest-building behavior was recorded as nesting scores, while spatial learning and memory behaviors were assessed using RAWM platform search errors and latencies. Results In the nest-building test, nest building significantly declined in nineteen 25-month-old mice compared to that of twenty-three 7-month-old mice. Meanwhile, nest building in 25-month-old mice was lower for eight male mice than for eleven female mice, while no significant gender differences were observed in nest building of 7-month-old mice. RAWM performance also declined in aged versus nonaged adult mice, while no significant gender differences were observed in average RAWM performance regardless of age. Conclusions In adult C57BL/6 mice, nest building is a sensitive indicator for detecting both age- and gender-based behavioral declines, while RAWM performance, an assessment of spatial learning and memory behaviors, is not sensitive to gender but significantly declines with aging. Therefore, for a C57BL/6 mouse model of aging, both nest building and RAWM should be useful to further study mechanisms involved in behavioral decline with aging.
Genome-Wide Investigation and Expression Profiling of HD-Zip Transcription Factors in Foxtail Millet (Setaria italica L.)

HD-Zip proteins represent the major transcription factors in higher plants, playing essential roles in plant development and stress responses. Foxtail millet is a crop to investigate the systems biology of millet and biofuel grasses and the HD-Zip gene family has not been studied in foxtail millet. For further investigation of the expression profile of the HD-Zip gene family in foxtail millet, a comprehensive genome-wide expression analysis was conducted in this study. We found 47 protein-encoding genes in foxtail millet using BLAST search tools; the putative proteins were classified into four subfamilies, namely, subfamilies I, II, III, and IV. Gene structure and motif analysis indicate that the genes in one subfamily were conserved. Promotor analysis showed that HD-Zip gene was involved in abiotic stress. Duplication analysis revealed that 8 (~17%) hdz genes were tandemly duplicated and 28 (58%) were segmentally duplicated; purifying duplication plays important roles in gene expansion. Microsynteny analysis revealed the maximum relationship in foxtail millet-sorghum and foxtail millet-rice. Expression profiling upon the abiotic stresses of drought and high salinity and the biotic stress of ABA revealed that some genes regulated responses to drought and salinity stresses via an ABA-dependent process, especially sihdz29 and sihdz45. Our study provides new insight into evolutionary and functional analyses of HD-Zip genes involved in environmental stress responses in foxtail millet.
Guiding Lights in Genome Editing for Inherited Retinal Disorders: Implications for Gene and Cell Therapy

Inherited retinal dystrophies (IRDs) are a leading cause of visual impairment in the developing world. These conditions present an irreversible dysfunction or loss of neural retinal cells, which significantly impacts quality of life. Due to the anatomical accessibility and immunoprivileged status of the eye, ophthalmological research has been at the forefront of innovative and advanced gene- and cell-based therapies, both of which represent great potential as therapeutic treatments for IRD patients. However, due to a genetic and clinical heterogeneity, certain IRDs are not candidates for these approaches. New advances in the field of genome editing using Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and CRISPR-associated protein (Cas) have provided an accurate and efficient way to edit the human genome and represent an appealing alternative for treating IRDs. We provide a brief update on current gene augmentation therapies for retinal dystrophies. Furthermore, we discuss recent advances in the field of genome editing and stem cell technologies, which together enable precise and personalized therapies for patients. Lastly, we highlight current technological limitations and barriers that need to be overcome before this technology can become a viable treatment option for patients.
Pathological molecular mechanism of symptomatic late-onset Fuchs endothelial corneal dystrophy by bioinformatic analysis

Fuchs endothelial corneal dystrophy (FECD) is a degenerative disease characterized by corneal endothelial decompensation. FECD causes corneal stromal and epithelial edema and progressively develops into bullous keratopathy, which can eventually lead to blindness. However, the exact pathogenesis is unknown. In this study, we performed an in-depth bioinformatic analysis of the dataset GSE74123 to determine the differentially expressed genes (DEGs) of symptomatic late-onset FECD compared with a normal control. Gene ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analysis were used to analyze the pathological molecular mechanism of FECD. We found that cell senescence, reactive oxygen species (ROS), the extracellular matrix (ECM), epithelial-mesenchymal transition (EMT) and immune response-related genes play an important role in the pathological development of symptomatic late-onset FECD. In addition, we revealed that down-regulated IL-6, enhanced NF-κB activity and a suite of orchestrated chemokine responses induce fibrocyte differentiation from monocyte to dendritic cell maturation. PI3K plays a key role in the molecular mechanism of symptomatic late-onset FECD. This study enhances our understanding of the molecular mechanism of FECD pathogenesis and will improve the diagnostics and therapy of FECD patients in the future.
Comparative analysis of various regularization techniques in the prediction of heart diseases

In the recent past it has been statistically proven that heart diseases are the largest contributing factor to the increase in mortality rate. Diagnosis of heart disease depends on a number of factors such as heart-rate, cholesterol levels, blood pressure, age and many other physiological factors. In most of the cases the diagnosis is done based on the experience and intuition of the doctor. This requires the doctor to be highly skilled and experienced in order to diagnose properly. It would be very helpful if we developed methods that could extract useful information from tonnes of clinical data. This paper reviews the L1/2 Logistic Regularization, Lasso, Elastic Net and Group Lasso regularization techniques, in order to select a subset of important features having the highest informative value in the prediction of heart diseases. Different regularization techniques select different subsets of features. This paper compares these techniques and finds out which is the most suitable method in the prediction of heart diseases.
Complete Genome Sequences of Two Salmonella Viruses, VSe11 and VSe102 (Family Myoviridae, Subfamily Ounavirinae), with a Very High Degree of Similarity

ABSTRACT Two lytic double-stranded DNA bacteriophages, VSe11 and VSe102, infecting broad-spectrum Salmonella enterica were isolated from the sewage of two different poultry farms. The phage genomes comprise 86,360 bp and 86,365 bp, respectively, with a G+C content of 39.0%, and both contain 129 putative coding sequences.
IoT application testing features based on the modelling network

In the article the features of testing devices and IoT applications are investigated. To make the problem clearer, the basic aspects of IoT applications architecture are considered. A set of requirements to the testing is presented, which must be considered when planning and organizing the testing process for IoT applications. The difficulties that arise during the testing phase of IoT applications and systems are described, same as mane differences from the classic application testing. As an approbation of the proposed test specifications, a full-scale experiment was conducted to test a fragment of the communication network in order to select an application protocol for a typical IoT, according to the results the conclusions are made.
The association between different molecular weights of hyaluronic acid and CHAD, HIF-1α, COL2A1 expression in chondrocyte cultures

The aim of the present study was to investigate the effects of three different formulations of hyaluronic acid (HA): Low molecular weight (MW) Sinovial One®, medium MW Viscoplus® and high MW Durolane®, on chondrocyte proliferation and collagen type II (COL2A1), hypoxia-inducible factor 1α (HIF-1α) and chondroadherin (CHAD) expression in primary chondrocyte cultures. Standard primary chondrocyte cultures were established from osteochondral tissues surgically obtained from 6 patients with gonarthrosis. Cell morphology was evaluated using an inverted light microscope; cell proliferation was determined with a MTT assay and confirmed with acridine orange/propidium iodide staining. Levels of CHAD, COL2A1 and HIF-1α expression were assessed using specific TaqMan gene expression assays. The results demonstrated the positive effect of HA treatment on cell proliferation, which was independent from the MW. COL2A1 expression increased in the medium and high MW HA treated groups. It was observed that HIF-1α expression increased in the high MW treated group alone. CHAD expression increased only in the medium MW HA treated group. Evaluation of gene expression revealed that levels of expression increased as the duration of HA application increased, in the medium and high MW HA treated groups. In terms of increased viability and proliferation, a longer duration of HA application was more effective. Taken together, it may be concluded that the administration of medium and high MW HA may be a successful way of treating diseases affecting chondrocytes in a clinical setting.
Ability, Learning and the Career Path of Cardiac Specialists

Prior research suggests physicians respond to incentives in quality programs, yet little is known about incentives that arise in physician labor markets absent intervention. This paper investigates the role of market learning by referring doctors in promoting specialist quality. I motivate the empirical work with a model of specialist careers under learning. I then compare careers of higher and lower quality specialists, using the universe of Medicare claims from cardiac specialists from 1996-2005 and a new empirical quality measure that is robust to patient sorting. I nd lower quality
SIGGRAPH : U : Attribute-preserving gamut mapping of measured

Reproducing the appearance of real-world materials using current printing technology is problematic. The reduced number of inks available define the printer’s limited gamut, creating distortions in the printed appearance that are hard to control. Gamut mapping refers to the process of bringing an outof-gamut material appearance into the printer’s gamut, while minimizing such distortions as much as possible. We present a novel two-step gamut mapping algorithm that allows users to specify which perceptual attribute of the original material they want to preserve (such as brightness, or roughness). In the first step, we work in the low-dimensional intuitive appearance space recently proposed by Serrano et al. [2016], and adjust achromatic reflectance via an objective function that strives to preserve certain attributes. From such intermediate representation, we then perform an image-based optimization including color information, to bring the BRDF into gamut. We show, both objectively and through a user study, how our method yields superior results compared to the state of the art, with the additional advantage that the user can specify which visual attributes need to be preserved.