Miracle-dz/UniFAR-FTUs huggingface dataset:
A test of Hardy‐Weinberg equilibrium in structured populations

Testing for Hardy‐Weinberg equilibrium (HWE) is used routinely as an important initial step for genotype data quality checking. Departure from HWE can be caused by many factors, such as genotyping errors, population stratification, and disease association, if we use affected individuals only. In a structured population, even if a marker is in HWE in each subpopulation, data may show departure from HWE if allele frequencies are different in different subpopulations and such a departure can be misinterpreted as a potential problem in genotyping quality, resulting in false exclusion from future analysis. In this article, we propose a new HWE test, a test for HWE in structured populations (HWES) that can assess departure from HWE and take into account of population stratification at the same time. Our proposed test can distinguish departure from HWE caused by population stratification and departure from HWE caused by other factors. We use simulation studies as well as applications to real data sets to evaluate the performance of the proposed test. Results show that, for a wide range of population structures, our proposed test has correct type I error rates while the traditional χ2 test will lead to false‐positive results. In homogenous populations, our proposed test has comparable power with the traditional χ2 test. Genet. Epidemiol. 2011. © 2011 Wiley Periodicals, Inc. 35:671‐678, 2011
Development of Hand Function and Precision Grip Control in Individuals With Cerebral Palsy: A 13-Year Follow-up Study

OBJECTIVE. Although children with cerebral palsy display large developmental differences in hand function from that of typically developing children by the age of 6 to 10 years, little is known about the developmental processes underlying hand function during subsequent development. In this study we investigated the development of manual dexterity in a timed motor task, the timing and amplitude of fingertip-force application during a precision grasping task, and the relationship between changes in these measures. We applied highly quantitative analytical approaches to determine if the fingertip-force application pattern and trial-to-trial variation of fingertip-force application change during development. METHODS. Twelve subjects with cerebral palsy (aged 6–8 years) participated in the first data-collection session conducted between 1989 and 1990. Ten of these subjects (5 with hemiplegia and 5 with diplegia, aged 19–21 years) returned between 2002 and 2003. Manual dexterity was measured by using timed tasks of the Jebsen-Taylor test of hand function. Subjects also lifted an object instrumented with force transducers while we measured the temporal coordination of fingertip coordination and the path ratio between the grip and vertical load-force trajectory (straightness). We used generalized procrustes analysis to determine if there were changes in shape of the force trajectory and intertrial variability. RESULTS. The Jebsen-Taylor test times decreased 45% from the first to the second data session. The overall time to complete the grip-lift task decreased 22%, mainly because of a faster transition from grasp to lift. The grip-force/load-force path ratios decreased from 1.7 to 1.35 (1 = straight line). Generalized procrustes analysis indicated a change in the shape and a decrease in variability in shape of the force-ratio path. CONCLUSIONS. Our results demonstrate that the efficiency in grasping had developed during a 13-year period for this small group of participants with cerebral palsy, which suggests that improvement in hand function occurs over a longer time frame than commonly would be expected.
An Enhanced Differential Evolution Based Energy Management System for Smart Grids

With the emergence of smart grid which has bidirectional communication capability plays a key role in maintaining balance between demand and supply. The major portion of energy consumed by residential sector creates a huge deficit between generation and consumption. Home energy management (HEM) system incorporation scheduling algorithm is an efficient alternate to cover this deficit by appropriate scheduling different appliances in residential sector. By using appliance scheduling scheme, utility get benefit by reducing peak demand and consumer got huge cost saving in its bill. These two objectives are achieved by continuously monitoring fluctuation in price signal, Recently, a stochastic based optimization techniques are used to meet the above objectives. In this work, the performance of HEM is evaluated by using two recent optimization i.e. differential evolution (DE) and enhanced differential evolution (EDE)algorithm. Finally, to validate the performance scheduling techniques in terms of peak to average ratio (PAR), total electricity cost, user comfort and energy consumption simulations are done in matlab. The simulations results prove that enhanced differential evolution algorithm performs efficiently than differential evolution algorithm.
Protein synthesis and secretion in the human epididymis and immunoreactivity with sperm antibodies

The synthesis and secretion of proteins in the different regions of the human epididymis were studied in vitro. Epididymal tissues obtained from patients undergoing castration for prostatic carcinoma or from cadavers were incubated in the presence of [35S]methionine, and the resulting radiolabeled proteins were analysed on SDS‐PAGE. The corpus region was found to be the most active segment in total protein synthesis. Significant qualitative and quantitative changes were observed in the pattern of proteins secreted from the different epididymal regions. To establish those epididymal proteins that interact with maturing sperm, the secreted products were immunoreacted with antibodies raised against a Triton X‐100 extract of ejaculated human sperm heads. The antibodies react mainly with the head region of ejaculated spermatozoa as judged by indirect immunofluorescence. Protein A‐gold labeling of freeze‐fracture images showed gold particle distribution on the sperm plasma membrane. Western blot analysis of the secreted proteins revealed four bands (66, 37, 32, and 29 kDa) in the proximal regions and six additional bands 80, 76, 48, 27, 22, and 17 (kDa) in the distal part of the epididymis. Immunoprecipitation of the secreted proteins with these antibodies revealed six radioactive bands of 170, 80, 76, 60, 48, and 37 kDa, which indicates that certain proteins of epididymal origin bind to the sperm plasma membrane.
Antibody to transforming growth factor-beta ameliorates tubular apoptosis in unilateral ureteral obstruction.

BACKGROUND Unilateral ureteral obstruction (UUO) is characterized by progressive renal atrophy, renal interstitial fibrosis, an increase in renal transforming growth factor-beta (TGF-beta), and renal tubular apoptosis. The present study was undertaken to determine the effect of a monoclonal antibody to TGF-beta (1D11) in UUO. METHODS Mechanical stretch was applied to tubular epithelial cells (NRK-52E) by a computer-assisted system. Three doses of 1D11 (either 0.5, 2, or 4 mg/rat) were administered to rats one day prior to UUO and every two days thereafter, and kidneys were harvested at day 13. Fibrosis was assessed by measuring tissue hydroxyproline and mRNA for collagen and fibronectin. Apoptosis was assessed with the terminal deoxy transferase uridine triphosphate nick end-labeling assay. TGF-beta levels were determined by bioassay. Western blot and immunostaining were used to identify proliferating cell nuclear antigen (PCNA), p53, bcl-2, and inducible nitric oxide synthase (iNOS). RESULTS Stretch significantly induced apoptosis in NRK-52E cells, which was accompanied by an increased release of TGF-beta; 1D11 (10 microg/mL) totally inhibited stretch-induced apoptosis. Control obstructed kidney contained 20-fold higher TGF-beta as compared with its unobstructed kidney; 1D11 neutralized tissue TGF-beta of the obstructed kidney. Control obstructed kidney exhibited significantly more fibrosis and tubular apoptosis than its unobstructed counterpart, which was blunted by 1D11. In contrast, 1D11 significantly increased tubular proliferation. p53 immunostaining was localized to renal tubular nuclei of control obstructed kidney and was diminished by 1D11. In contrast, bcl-2 was up-regulated in the 1D11-treated obstructed kidney. Total NOS activity and iNOS activity of the obstructed kidney were increased by 1D11 treatment. CONCLUSION The present study strongly suggests that an antibody to TGF-beta is a promising agent to prevent renal tubular fibrosis and apoptosis in UUO.
Radio resource management issues for 3G and beyond cellular wireless networks

Radio resource management (RRM) in the next generation wireless network system will have features and requirements that are quite distinct from current systems, mostly designed for non-heterogeneous and non-shared networks. Such features include radio resource sharing which is considered as one of the main future issues of RRM as network evolves towards 4G Radio resource sharing has an impact on system design in general and on radio resource management in particular. This paper presents a general RRM for 3G and beyond mobile wireless network supporting multi-services, referred to as general call admission control (GCAC). The aim of the proposed GCAC algorithm is to guarantee the required quality of service (QoS) and to maintain higher resource utilization. Simulation results indicate that the proposed GCAC provides higher resource utilization under all load conditions leading in turn to increased revenue. In addition, a higher quality of service for traffic is provided especially when we differentiate between the traffic classes.
Type 3 Muscarinic Receptors Contribute to Clearance of Citrobacter rodentium

Background:The role of muscarinic receptors in mucosal homeostasis, response to enteric pathogens, and modulation of immune cell function is undefined. Methods:The contribution of type 3 muscarinic receptors (M3R) to mucosal homeostasis within the colon and host defense against Citrobacter rodentium was determined in uninfected and C. rodentium–infected WT and M3R-deficient (Chrm3−/−) mice. In addition, WT and Chrm3−/− bone marrow-derived macrophages were studied to determine the ability of M3R to modulate macrophage phenotype and function. Results:In Chrm3−/− mice, clearance of C. rodentium was delayed despite an amplified TH1/TH17 response. Delayed clearance of C. rodentium from Chrm3−/− mice was associated with prolonged adherence of bacteria to colonic mucosa, decreased goblet cell number, and decreased mucin 2 gene expression. Treatment of bone marrow-derived macrophages with bethanechol, a muscarinic-selective agonist, induced a classically activated macrophage phenotype, which was dependent on M3R expression. Chrm3−/− bone marrow-derived macrophages retained their ability to attain a classically activated macrophage phenotype when treated with the TH1 cytokine IFN-&ggr;. Conclusions:In Chrm3−/− mice, mucin production is attenuated and is associated with prolonged adherence of C. rodentium to colonic mucosa. The immune response, as characterized by production of TH1/TH17 cytokines, in C. rodentium–infected Chrm3−/− mice is intact. In addition, M3R activity promotes the development of classically activated macrophages. Our data establish a role for M3R in host defense against C. rodentium through effects on goblet cell mucus production and in the modulation of macrophage phenotype and function.
Complex relationship between BOLD signal and synchronization/desynchronization of human brain MEG oscillations

Functional magnetic resonance imaging (fMRI) depends on the coupling of cerebral blood flow, energy demand, and neural activity. The precise nature of this interaction, however, is poorly understood. A positive correlation between BOLD‐response and cortically generated local field potentials, which reflect the weighted average of synchronized dentrosomatic components of pyramidal synaptic signals, has been demonstrated. Likewise, positive BOLD‐responses have been reported in conjunction with scalp‐recorded synchronized electromagnetic activity by a number of groups. However, it is not yet clear how the opposite electromagnetic pattern, i.e. cortical desynchronization, is related to the BOLD signal. To address this question, we conducted a combined event‐related fMRI and 275 sensor whole‐head MEG study during identical visual two‐choice reaction time task conditions in 10 human subjects. We found complex sequences of MEG‐synchronization and desynchronization across a wide frequency range in the visual and motor area in close correspondence with “locales” of positive BOLD‐responses. These results indicate that a correspondence of positive BOLD‐responses is not exclusively found for cortical synchronization but also for desynchronization, suggesting that the relationship between BOLD signals and electromagnetic activity might be more complex than previously thought. Hum Brain Mapp 2006. © 2006 Wiley‐Liss, Inc.
Gene Networks and Chromatin and Transcriptional Regulation of the Phaseolin Promoter in Arabidopsis[C][W]

Modification of tissue-specific inhibitory chromatin is critical for the regulation of plant developmental processes. Using a combination of functional genomics, gene network analysis, and genetic experiments, this study identified RLT2 and AIL5 proteins as essential regulators of seed-specific transcription, providing insight into the regulation of seed development. The complete lack of seed storage protein expression in vegetative tissues and robust expression during embryogenesis makes seed development an ideal system to study tissue-specific expression of genes. The promoter for the Phaseolin (phas) gene, which encodes the major seed storage protein in bean (Phaseolus vulgaris), is activated in two sequential steps: Phaseolus vulgaris ABI3-like factor (Pv-ALF)–dependent potentiation and abscisic acid–mediated activation. In this study, a heterologous in vivo Pv-ALF/phas-GUS (for β-glucuronidase) expression system in transgenic Arabidopsis thaliana leaves was used in conjunction with the powerful RNA-Seq approach to capture transcriptional landscapes of phas promoter expression. Remarkably, expression of over 1300 genes from 11 functional categories coincided with changes in the transcriptional status of the phas promoter. Gene network analysis of induced genes and artificial microRNA–mediated loss-of-function genetic assays identified transcriptional regulators RINGLET 2 (RLT2) and AINTEGUMENTA-LIKE 5 (AIL5) as being essential for phas transcription. Pv-ALF binding to the RLT2 and AIL5 promoter regions was confirmed by electrophoretic mobility shift assay. RLT2 and AIL5 knockdown lines displayed reduced expression of several endogenous seed genes, suggesting that these factors are involved in activation of endogenous Arabidopsis seed storage gene expression. Overall, the identification of these key factors involved in phas activation provides important insight into the two-step transcriptional regulation of seed-specific gene expression.
Laterality and School Achievement: Interactions between Familial Handedness and Assessed Laterality

179 8- to 12-yr. -old children received hand-preference, eye-preference, dichotic (digits and nonverbal sounds) tests, and the Wide Range Achievement Test. These data and those from previous studies suggest that brain organization for receptive language laterality can be predicted by familial handedness in conjunction with assessed hand-eye preference. A model of optimum functional ear laterality patterns within a given brain organization is advanced. For example, the “typical” pattern of a right-ear (left-hemisphere) advantage for verbal stimuli was associated with high achievement scores only for right-handed individuals with a family history of dextrality.
Therapeutic targeting of transcription in acute promyelocytic leukemia by use of an inhibitor of histone deacetylase.

BACKGROUND Acetylation of DNA-associated histones is linked to activation of gene transcription, whereas histone deacetylation is associated with transcriptional repression. Recent studies have shown that inhibitors of histone deacetylases can relieve transcriptional repression caused by the products of certain oncogenes. We tested whether these findings could be applied clinically to a patient with highly resistant acute promyelocytic leukemia. METHODS A patient who had experienced multiple relapses was treated with all-trans-retinoic acid alone and in combination with sodium phenylbutyrate, an inhibitor of histone deacetylases. Immunohistochemistry and western blot analysis were used to assay for histone hyperacetylation in mononuclear cells from the patient's blood and bone marrow. Marrow mononuclear cells and reverse transcription-polymerase chain reaction (RT-PCR) analysis of messenger RNA encoded by the PML/RAR-alpha oncogene were used to assess minimal residual disease. RESULTS The patient proved clinically resistant to treatment with all-trans-retinoic acid alone. However, 23 days after sodium phenylbutyrate was added to the treatment regimen, visible leukemic cells had been eliminated from her bone marrow, and she achieved a complete clinical and cytogenetic remission shortly thereafter. With a second treatment course, analysis for minimal residual disease by RT-PCR proved negative. Immunofluorescence and western blot analysis showed that phenylbutyrate caused a time-dependent increase in histone acetylation in blood and bone marrow mononuclear cells. CONCLUSIONS Clinical treatment with an inhibitor of histone deacetylase induces histone hyperacetylation in target cells and may restore sensitivity to the anti-leukemic effects of all-trans-retinoic acid in acute promyelocytic leukemia. Similar therapy may prove useful in other neoplastic diseases that are associated with oncogenic repression of gene transcription due to recruitment of histone deacetylases.
Modeling Training Effects Using a Human Performance Taxonomy

Objective: The aim of this study was to characterize skill acquisition during training and skill retention as a function of training strategy, retention period, and task type in the form of a numerical model and then apply that model to make predictions of performance on an unknown task. Background: Complex systems require efficient and effective training programs for the humans who operate them in discontinuous fashion. Although there are several constructs for learning theory, models that enable analysts to predict training outcomes are needed during the design of training programs. Method: This study involved 60 participants who were trained on five tasks relevant to RQ-1 Predator unmanned aircraft system sensor operators by one of three strategies that represented a continuum of instructor interactivity. After training, performance data for all five tasks were collected. Participants completed the same tasks 30 or 60 days later to determine skill retention and the rate at which task proficiency was reacquired. Results: Models built from tasks that isolate human performance channels adequately predicted performance on a task that combined those channels. Conclusion: Models that predict performance on tasks that isolate human performance channels can be used to make predictions on tasks that draw on multiple channels. This model provided a distribution of performance data that was statistically similar to actual performance data. Application: System designers trained with human performance data on a set of tasks can apply those tasks’ characteristics to future tasks to make reasonably accurate performance predictions, thereby allowing the designers to make early decisions regarding training strategy to teach those tasks.
A review of numerical and experimental compensation techniques for skull-induced phase aberrations in transcranial focused ultrasound

Abstract The development of phased array transducers and their integration with magnetic resonance (MR) guidance and thermal monitoring has established transcranial MR-guided focused ultrasound (tcMRgFUS) as an attractive non-invasive modality for neurosurgical interventions. The presence of the skull, however, compromises the efficiency of transcranial FUS (tcFUS) therapy, as its heterogeneous nature and acoustic characteristics induce significant phase aberrations and energy attenuation, especially at the higher acoustic frequencies employed in tcFUS thermal therapy. These aberrations may distort and shift the acoustic focus as well as induce heating at the patient’s scalp and skull bone. Phased array transducers feature hundreds of elements that can be driven individually, each with its own phase and amplitude. This feature allows for compensation of skull-induced aberrations by calculation and application of appropriate phase and amplitude corrections. In this paper, we illustrate the importance of precise refocusing and provide a comprehensive review of the wide variety of numerical and experimental techniques that have been used to estimate these corrections.
Activation of the TRPV4 Ion Channel Is Enhanced by Phosphorylation

The TRPV4 (transient receptor potential vanilloid 4) ion channel, a member of the vanilloid subfamily of the transient receptor potential channels, is activated by membrane stretch, by non-noxious warm temperatures, and by a range of chemical activators. In the present study we examined the role of phosphorylation in modulating the activation of TRPV4. We expressed TRPV4 in HEK293 cells and activated the channel by cell swelling in a hypotonic solution. TRPV4 channel activation and serine phosphorylation were enhanced by exposure to the protein kinase C (PKC) activator phorbol 12-myristate 13-acetate or by application of bradykinin, which activates PKC via a G-protein-coupled mechanism. The enhancement was inhibited by the PKC inhibitors staurosporine, bisindolylmaleimide I, and rottlerin or by mutation of the serine/threonine residues Ser162, Thr175, and Ser189. The adenylate cyclase activator forskolin also enhanced activation of TRPV4, and the enhancement was antagonized by the selective cyclic AMP-dependent protein kinase (PKA) inhibitor H89 or by mutation of serine residue Ser824. Sensitization of TRPV4 by both PKC and PKA depended on the scaffolding protein AKAP79, because channel activation and phosphorylation were enhanced by co-transfection of AKAP79 and were antagonized by removal of AKAP79 using small interfering RNA. We conclude that the serine/threonine kinases PKC and PKA enhance activation of the TRPV4 ion channel by phosphorylation at specific sites and that phosphorylation depends on assembly of PKC and PKA by AKAP79 into a signaling complex with TRPV4.
Value of information methods for assessing a new diagnostic test

Value‐of‐information methods are applied to assess the evidence in support of a new diagnostic test and, where the evidence is insufficient for decision making, to determine the optimal sample size for future studies. Net benefit formulations are derived under various diagnostic and treatment scenarios. The expressions for the expected opportunity loss of adopting strategies that include the new test are given. Expressions for the expected value of information from future studies are derived. One‐sample and two‐sample designs, with or without known prevalence, are considered. An example is given. Copyright © 2014 John Wiley & Sons, Ltd.