Miracle-dz/UniFAR-FTUs huggingface dataset:
Phenotype harmonization and cross‐study collaboration in GWAS consortia: the GENEVA experience

Genome‐wide association study (GWAS) consortia and collaborations formed to detect genetic loci for common phenotypes or investigate gene‐environment (G*E) interactions are increasingly common. While these consortia effectively increase sample size, phenotype heterogeneity across studies represents a major obstacle that limits successful identification of these associations. Investigators are faced with the challenge of how to harmonize previously collected phenotype data obtained using different data collection instruments which cover topics in varying degrees of detail and over diverse time frames. This process has not been described in detail. We describe here some of the strategies and pitfalls associated with combining phenotype data from varying studies. Using the Gene Environment Association Studies (GENEVA) multi‐site GWAS consortium as an example, this paper provides an illustration to guide GWAS consortia through the process of phenotype harmonization and describes key issues that arise when sharing data across disparate studies. GENEVA is unusual in the diversity of disease endpoints and so the issues it faces as its participating studies share data will be informative for many collaborations. Phenotype harmonization requires identifying common phenotypes, determining the feasibility of cross‐study analysis for each, preparing common definitions, and applying appropriate algorithms. Other issues to be considered include genotyping timeframes, coordination of parallel efforts by other collaborative groups, analytic approaches, and imputation of genotype data. GENEVA's harmonization efforts and policy of promoting data sharing and collaboration, not only within GENEVA but also with outside collaborations, can provide important guidance to ongoing and new consortia. Genet. Epidemiol. 35:159‐173, 2011. © 2011 Wiley‐Liss, Inc.
Identifying Inhibitors of Inflammation: A Novel High-Throughput MALDI-TOF Screening Assay for Salt-Inducible Kinases (SIKs)

Matrix-assisted laser desorption/ionization time-of-flight (MALDI TOF) mass spectrometry has become a promising alternative for high-throughput drug discovery as new instruments offer high speed, flexibility and sensitivity, and the ability to measure physiological substrates label free. Here we developed and applied high-throughput MALDI TOF mass spectrometry to identify inhibitors of the salt-inducible kinase (SIK) family, which are interesting drug targets in the field of inflammatory disease as they control production of the anti-inflammatory cytokine interleukin-10 (IL-10) in macrophages. Using peptide substrates in in vitro kinase assays, we can show that hit identification of the MALDI TOF kinase assay correlates with indirect ADP-Hunter kinase assays. Moreover, we can show that both techniques generate comparable IC50 data for a number of hit compounds and known inhibitors of SIK kinases. We further take these inhibitors to a fluorescence-based cellular assay using the SIK activity-dependent translocation of CRTC3 into the nucleus, thereby providing a complete assay pipeline for the identification of SIK kinase inhibitors in vitro and in cells. Our data demonstrate that MALDI TOF mass spectrometry is fully applicable to high-throughput kinase screening, providing label-free data comparable to that of current high-throughput fluorescence assays.
Nonparametric Model Comparison and Uncertainty Evaluation for Signal Strength Indoor Location

Indoor location (IL) using received signal strength (RSS) is receiving much attention, mainly due to its ease of use in deployed IEEE 802.11b (Wi-Fi) wireless networks. Fingerprinting is the most widely used technique. It consists of estimating position by comparison of a set of RSS measurements, made by the mobile device, with a database of RSS measurements whose locations are known. However, the most convenient data structure to be used and the actual performance of the proposed fingerprinting algorithms are still controversial. In addition, the statistical distribution of indoor RSS is not easy to characterize. Therefore, we propose here the use of nonparametric statistical procedures for diagnosis of the fingerprinting model, specifically: 1) A nonparametric statistical test, based on paired bootstrap resampling, for comparison of different fingerprinting models and 2) new accuracy measurements (the uncertainty area and its bias) which take into account the complex nature of the fingerprinting output. The bootstrap comparison test and the accuracy measurements are used for RSS-IL in our Wi-Fi network, showing relevant information relating to the different fingerprinting schemes that can be used.
Myostatin-like proteins regulate synaptic function and neuronal morphology

Growth factors of the TGFβ superfamily play key roles in regulating neuronal and muscle function. Myostatin (or GDF8) and GDF11 are potent negative regulators of skeletal muscle mass. However, expression of myostatin and its cognate receptors in other tissues, including brain and peripheral nerves, suggests a potential wider biological role. Here, we show that Myoglianin (MYO), the Drosophila homolog of myostatin and GDF11, regulates not only body weight and muscle size, but also inhibits neuromuscular synapse strength and composition in a Smad2-dependent manner. Both myostatin and GDF11 affected synapse formation in isolated rat cortical neuron cultures, suggesting an effect on synaptogenesis beyond neuromuscular junctions. We also show that MYO acts in vivo to inhibit synaptic transmission between neurons in the escape response neural circuit of adult flies. Thus, these anti-myogenic proteins act as important inhibitors of synapse function and neuronal growth. Summary: Myostatin-like proteins can modulate neuromuscular synapse strength as well as synaptogenesis beyond neuromuscular junctions, highlighting a key role for these proteins in synapse function and neuronal growth.
Comparative Effect of Grape Seed Extract (Vitis Vinifera) and Ascorbic Acid in Oxidative Stress Induced by On-pump Coronary Artery Bypass Surgery

Background: This study aimed to test the beneficial effect of grape seed extract (GSE) (Vitis vinifera) and Vitamin C in oxidative stress and reperfusion injury induced by cardiopulmonary bypass (CPB) in coronary artery bypass surgery. Patients and Methods: In this randomized trial, 87 patients undergoing elective and isolated coronary bypass surgery included. The patients were randomly assigned into three groups (n = 29 each): (1) Control group with no treatment, (2) GSE group who received the extract 24 h before operation, 100 mg every 6 h, orally, (3) Vitamin C group who received 25 mg/kg Vitamin C through CPB during surgery. Blood samples were taken from coronary sinus at (T1) just before aortic cross clamp; (T2) just before starting controlled aortic root reperfusion; and (T3) 10 min after root reperfusion. Some clinical parameters and biochemical markers were compared among the groups. Results: There were significant differences in tracheal intubation times, sinus rhythm return, and left ventricular function between treatment groups compared with control (P < 0.05). Total antioxidant capacity was higher (P < 0.05) in both grape seed and Vitamin C groups at T2 and T3 times. In reperfusion period, malondialdehyde level was increased in control group; however, it was significantly lower for the grape seed group (P = 0.04). The differences in the mean levels of superoxide dismutase and glutathione peroxidase among the three groups were not significant (P > 0.05 in all cases). Conclusions: In our patients, GSE and Vitamin C had antioxidative effects and reduced deleterious effects of CPB during coronary artery bypass grafting surgery.
The Role of Parenting and Family Factors in the Developmental Catch-Up for Children Adopted Internationally

ABSTRACT Internationally adopted children are at greater risk for cognitive difficulties. While age at adoption is an established significant predictor of cognitive outcomes, considerable variation persists. The present study focused on whether parenting and family factors explain additional variance in cognitive and linguistic catch-up in this group of children. In total, 46 children were examined at two time points, approximately 12 months apart. Cognitive and linguistic abilities were measured at both time points, with parenting and family factors examined at follow-up, using hierarchical linear regression. Age at adoption and baseline cognitive abilities were the best predictors of cognitive and linguistic catch-up; parenting and family factors generally did not account for a significant increase in explained variance.
Silencing of human papillomavirus (HPV) E6/E7 oncogene expression affects both the contents and the amounts of extracellular microvesicles released from HPV‐positive cancer cells

The human papillomavirus (HPV) E6/E7 oncogenes play a crucial role in the HPV‐induced carcinogenesis. In this study, the authors investigated whether silencing of endogenous HPV E6/E7 expression may influence the contents or amounts of extracellular microvesicles (eMVs) released from HPV‐positive cancer cells. It was found that eMVs secreted from HeLa cells are enriched for Survivin protein. RNA interference studies revealed that maintenance of both intracellular and microvesicular Survivin amounts was strongly dependent on continuous E6/E7 expression. This indicates that intracellular HPV activities are translated into visible alterations of protein contents in eMVs. Besides Survivin, eMVs from HeLa cells contain additional members of the inhibitor of apoptosis protein (IAP) family (XIAP, c‐IAP1 and Livin). In contrast, no evidence for the presence of the HPV E6 and E7 oncoproteins in eMVs was obtained. Moreover, it was found that silencing of HPV E6/E7 expression led to a significant increase of exosomes—representing eMVs of endocytic origin—released from HeLa cells. This effect was associated with the reinduction of p53, stimulation of the p53 target genes TSAP6 and CHMP4C that can enhance exosome production and induction of senescence. Taken together, these results show that silencing of HPV E6/E7 oncogene expression profoundly affects both the composition and amounts of eMVs secreted by HPV‐positive cancer cells. This indicates that HPVs can induce molecular signatures in eMVs that may affect intercellular communication and could be explored for diagnostic purposes.
Preparation and characterization of PEM-coated alginate microgels for controlled release of protein

In this study, calcium-alginate microgels coated with a polyelectrolyte multilayer (PEM) were fabricated as a controlled-release system. This system was constructed via an electrostatic droplet generation technique followed by a layer-by-layer (LbL) self-assembly technique. The electrostatic droplet generation technique was reported as an easy method of preparing microgels, due to their mild preparation conditions and ability to preserve the biological activity of the encapsulated drugs. With the LbL self-assembly technique, the PEM could be fabricated on the microgels attributed to the electrostatic attraction between positive-charged chitosan (Chi) and negative-charged dextran sulfate (Dex). The properties of the prepared microgels were investigated using dynamic laser scattering (DLS), scanning electron microscopy (SEM), x-ray photoelectron spectroscopy (XPS), Fourier transform infrared (FTIR) spectrum and zeta potential analyzer. In vitro release study indicated that the initial burst release of the bovine serum albumin (BSA) from PEM-coated microgels was less compared to the uncoated microgels (19% versus 31% in 24 h). In addition, the sustained release of BSA from the PEM-coated microgels was recorded up to 1 month without any damage to BSA integrity. Thus, our results demonstrated that the PEM-coated microgels not only prolonged the release time, but also relieved the initial burst problem to some degree and preserved the biological activity of the encapsulated drugs. Moreover, the release rate of BSA could be regulated by controlling the number of deposited layers. In conclusion, this study presented an easy yet effective method for the controlled, sustained release of biological macromolecules.
The Neural Correlates of Mental Rotation Abilities in Cannabis-Abusing Patients with Schizophrenia: An fMRI Study

Growing evidence suggests that cannabis abuse/dependence is paradoxically associated with better cognition in schizophrenia. Accordingly, we performed a functional magnetic resonance imaging (fMRI) study of visuospatial abilities in 14 schizophrenia patients with cannabis abuse (DD), 14 nonabusing schizophrenia patients (SCZ), and 21 healthy controls (HCs). Participants performed a mental rotation task while being scanned. There were no significant differences in the number of mistakes between schizophrenia groups, and both made more mistakes on the mental rotation task than HC. Relative to HC, SCZ had increased activations in the left thalamus, while DD patients had increased activations in the right supramarginal gyrus. In both cases, hyper-activations are likely to reflect compensatory efforts. In addition, SCZ patients had decreased activations in the left superior parietal gyrus compared to both HC and DD patients. This latter result tentatively suggests that the neurophysiologic processes underlying visuospatial abilities are partially preserved in DD, relative to SCZ patients, consistently with the findings showing that cannabis abuse in schizophrenia is associated with better cognitive functioning. Further fMRI studies are required to examine the neural correlates of other cognitive dysfunctions in schizophrenia patients with and without comorbid cannabis use disorder.
Structures of three substituted arenesulfonamides from X-ray powder diffraction data using the differential evolution technique.

The structures of three substituted arenesulfonamides have been solved from laboratory X-ray powder diffraction data, using a new direct-space structure solution method based on a differential evolution algorithm, and refined by the Rietveld method. In 2-toluenesulfonamide, C(7)H(9)NO(2)S (I) (tetragonal I4(1)/a, Z = 16), the molecules are linked by N-H.O=S hydrogen bonds into a three-dimensional framework. In 3-nitrobenzenesulfonamide, C(6)H(6)N(2)O(4)S (II) (monoclinic P2(1), Z = 2), N-H.O=S hydrogen bonds produce molecular ladders, which are linked into sheets by C-H.O=S hydrogen bonds: the nitro group does not participate in the hydrogen bonding. Molecules of 4-nitrobenzenesulfonamide, C(6)H(6)N(2)O(4)S (III) (monoclinic P2(1)/n, Z = 4), are linked into sheets by four types of hydrogen bond, N-H.O=S, N-H.O(nitro), C-H.O=S and C-H.O(nitro), and the sheets are weakly linked by aromatic pi.pi stacking interactions.
Limits to the role of palindromy in deletion formation

We tested the effect of palindromy on deletion formation. This involved a study of reversion of insertion mutations in the pBR322 amp gene at a site where deletions end either in 9-bp direct repeats or in adjoining 4-bp direct repeats. Inserts of palindromic DNAs ranging from 10 to more than 26 bp and related nonpalindromic DNAs were compared. The frequency of deletions (selected as Ampr revertants) was stimulated by palindromy only at lengths greater than 26 bp. The 4-bp direct repeats, one component of which is located in the palindromic insert, were used preferentially as deletion endpoints with palindromes of at least 18 bp but not of 16 or 10 bp. We interpret these results with a model of slippage during DNA replication. Because deletion frequency and deletion endpoint location depend differently on palindrome length, we propose that different factors commit a molecule to undergo deletion and determine exactly where deletion endpoints will be.
Nonlinear Formation-Keeping and Mooring Control of Multiple Autonomous Underwater Vehicles

This paper deals with the nonlinear formation-keeping and mooring control of multiple autonomous underwater vehicles (AUVs) in chained form. The AUV formation under consideration is constrained by the desired separations and orientations of follower AUVs with respect to a time-varying leader AUV. First, a time-varying, smooth feedback control law for the formation-keeping of multiple nonholonomic AUVs is presented by taking advantage of the Lyapunov direct method. Its asymptotical convergence to a desired formation trajectory prescribed by a leader-follower pair is guaranteed. Second, a time-varying, smooth feedback control law with asymptotic stability is designed to collaboratively moor the follower AUV to its desired docking position and orientation with respect to the leader by using the integrator backstepping method. Third, the realization problems of physical AUV system and singularity avoidance are investigated for applying the aforementioned control laws to a real formation system of AUVs. Finally, simulation results are provided to illustrate the effectiveness of the proposed control laws
Response of Different Genotypes of Faba Bean Plant to Drought Stress

Drought stress is one of the major abiotic stresses that are a threat to crop production worldwide. Drought stress impairs the plants growth and yield. Therefore, the aim of the present experiment was to select the tolerant genotype/s on the basis of moprpho-physiological and biochemical characteristics of 10 Vicia faba genotypes (Zafar 1, Zafar 2, Shebam, Makamora, Espan, Giza Blanka, Giza 3, C4, C5 and G853) under drought stress. We studied the effect of different levels of drought stress i.e., (i) normal irrigation (ii) mild stress (iii) moderate stress, and (iv) severe stress on plant height (PH) plant−1, fresh weight (FW) and dry weight (DW) plant−1, area leaf−1, leaf relative water content (RWC), proline (Pro) content, total chlorophyll (Total Chl) content, electrolyte leakage (EL), malondialdehyde (MDA), hydrogen peroxide (H2O2) content, and activities of catalase (CAT), peroxidase (POD) and superoxide dismutase (SOD) of genotypes of faba bean. Drought stress reduced all growth parameters and Total Chl content of all genotypes. However, the deteriorating effect of drought stress on the growth performance of genotypes “C5” and “Zafar 1” were relatively low due to its better antioxidant enzymes activities (CAT, POD and SOD), and accumulation of Pro and Total Chl, and leaf RWC. In the study, genotype “C5” and “Zafar 1” were found to be relatively tolerant to drought stress and genotypes “G853” and “C4” were sensitive to drought stress.
Gonadotrophin‐Releasing Hormone (GnRH) Release in Marmosets I: In Vivo Measurement in Ovary‐Intact and Ovariectomised Females

In vivo hypothalamic gonadotrophin‐releasing hormone (GnRH) release was characterised for the first time in a New World primate. A nonterminal and repeatable push‐pull perfusion (PPP) technique reliably measured GnRH in conscious common marmoset monkeys. Nineteen adult females (n = 8 ovary‐intact in the mid‐follicular phase; n = 11 ovariectomised) were fitted with long‐term cranial pedestals, and a push‐pull cannula was temporarily placed in unique locations within the pituitary stalk‐median eminence (S‐ME) 2 days prior to each PPP session. Marmosets underwent 1–3 PPPs (32 PPPs in total) lasting up to 12 h. Plasma cortisol levels were not elevated in these habituated marmosets during PPP, and PPP did not disrupt ovulatory cyclicity or subsequent fertility in ovary‐intact females. GnRH displayed an organised pattern of release, with pulses occurring every 50.0 ± 2.6 min and lasting 25.4 ± 1.3 min. GnRH pulse frequency was consistent within individual marmosets across multiple PPPs. GnRH mean concentration, baseline concentration and pulse amplitude varied predictably with anatomical location of the cannula tip within the S‐ME. GnRH release increased characteristically in response to a norepinephrine infusion and decreased abruptly during the evening transition to lights off. Ovary‐intact (mid‐follicular phase) and ovariectomised marmosets did not differ significantly on any parameter of GnRH release. Overall, these results indicate that PPP can be used to reliably assess in vivo GnRH release in marmosets and will be a useful tool for future studies of reproductive neuroendocrinology in this small primate.
Pipeline-Based Parallel Framework for Mass File Processing

Currently, there exists billions of files on the Internet, such as pictures, web pages, audio and video files, etc., and the number is still growing rapidly. These huge amount of files need to be processed by some applications as quickly as possible with parallel processing. With the increasing of cores in processors, parallel programming becomes more complex. The behavior that multiple parallel processes/threads access files simultaneously may interfere with each other and cause extra performance loss. Consequently, this paper proposes a pipeline-based parallel framework for mass file processing, in which file processing is divided into multiple stages to compose a pipeline. Files flow through these stages one by one, and the interferences in file-accessing are avoided. Moreover, the parallel programming can be simplified by means of parallel frameworks and programming interfaces. Experiments with one real-world application and some micro-benchmarks show that the framework can efficiently improve system performance.
IUGR Alters Postnatal Rat Skeletal Muscle Peroxisome Proliferator-Activated Receptor-γ Coactivator-1 Gene Expression in a Fiber Specific Manner

Uteroplacental insufficiency and subsequent intrauterine growth retardation (IUGR) increase the risk of insulin resistance in humans and rats. Aberrant skeletal muscle lipid metabolism contributes to the pathogenesis of insulin resistance. Peroxisome proliferator-activated receptor-γ co-activator-1 (PGC-1) is a transcriptional co-activator that affects gene expression of key lipid metabolizing enzymes such as carnitine palmitoyl-transferase I (mCPTI). Because gene expression of lipid metabolizing enzymes is altered in IUGR postnatal skeletal muscle, and we hypothesized that PGC-1 expression would be similarly affected. To prove this hypothesis, bilateral uterine artery ligation and sham surgery were used to produce IUGR and control rats respectively. Western Blotting demonstrated that PGC-1 hind limb skeletal muscle protein levels were increased in perinatal and postnatal IUGR rats. Conventional RT-PCR demonstrated that PGC-1 mRNA levels were similarly increased in perinatal hind limb skeletal muscle and juvenile extensor digitorum longus (EDL), but were decreased in juvenile soleus. Because a gender specific trend was noted in PGC-1 mRNA levels, real time RT-PCR was used for further differentiation. Real time RT-PCR revealed that changes in postnatal skeletal muscle PGC-1 expression were more marked in male IUGR rats versus female IUGR rats. Down stream targets of PGC-1 followed a similar pattern of expression. We conclude that PGC-1 expression is altered in rat IUGR skeletal muscle and speculate that it contributes to the pathogenesis of insulin resistance in the IUGR rat.