Miracle-dz/UniFAR-FTUs huggingface dataset:
Absence of Maternal Methylation in Biparental Hydatidiform Moles from Women with NLRP7 Maternal-Effect Mutations Reveals Widespread Placenta-Specific Imprinting

Familial recurrent hydatidiform mole (RHM) is a maternal-effect autosomal recessive disorder usually associated with mutations of the NLRP7 gene. It is characterized by HM with excessive trophoblastic proliferation, which mimics the appearance of androgenetic molar conceptuses despite their diploid biparental constitution. It has been proposed that the phenotypes of both types of mole are associated with aberrant genomic imprinting. However no systematic analyses for imprinting defects have been reported. Here, we present the genome-wide methylation profiles of both spontaneous androgenetic and biparental NLRP7 defective molar tissues. We observe total paternalization of all ubiquitous and placenta-specific differentially methylated regions (DMRs) in four androgenetic moles; namely gain of methylation at paternally methylated loci and absence of methylation at maternally methylated regions. The methylation defects observed in five RHM biopsies from NLRP7 defective patients are restricted to lack-of-methylation at maternal DMRs. Surprisingly RHMs from two sisters with the same missense mutations, as well as consecutive RHMs from one affected female show subtle allelic methylation differences, suggesting inter-RHM variation. These epigenotypes are consistent with NLRP7 being a maternal-effect gene and involved in imprint acquisition in the oocyte. In addition, bioinformatic screening of the resulting methylation datasets identified over sixty loci with methylation profiles consistent with imprinting in the placenta, of which we confirm 22 as novel maternally methylated loci. These observations strongly suggest that the molar phenotypes are due to defective placenta-specific imprinting and over-expression of paternally expressed transcripts, highlighting that maternal-effect mutations of NLRP7 are associated with the most severe form of multi-locus imprinting defects in humans.
English in the Kingdom of Saudi Arabia

This paper examines the history, politics and discourses around the (teaching of) English language in the Kingdom of Saudi Arabia (KSA). In addition to discussing the issues and debates around English language, this paper also looks at whether and how English has been localised to suit the local needs and practices. Based on an analysis of English language textbooks used in KSA, the paper shows that Saudi English mostly follows and ascribes to the grammatical norms of standard Englishes. The paper does identify some deviations in the grammar of English in these textbooks; however, these are within the range of features of varieties of Englishes found in other Inner, Outer and Expanding circle varieties of Englishes. The paper then identifies a number of discursive and multimodal features of Saudi English that are much more locally oriented and reflect local cultural norms and practices. The findings of this paper suggest that English in Saudi Arabia is in the process of being nativised and that this Saudi English reflects recognisably local cultural, religious and social values and beliefs.
A Methodology for Introducing Competitive Anxiety and Pressure in VR Sports Training

Athletes' performances are influenced by internal and external factors, including their psychological state and environmental factors, especially during competition. As a consequence, current training programs include stress management. In this paper, we explore whether highly immersive systems can be used for such training programs. First, we propose methodological guidelines to design sport training scenarios both on considering the elements that a training routine must have, and how external factors might influence the participant. The proposed guidelines are based on Flow and social-evaluative threat theories. Second, to illustrate and validate our methodology, we designed an experimental setup reproducing a ten meter Olympic pistol shooting. We analyzed whether changes in the environment are able to induce changes in user performance, physiological responses and the subjective perception of the task. The simulation included stressors in order to raise a social-evaluative threat, such as aggressive public behavior or unforced errors, increasing the pressure while performing the task. The results showed significant differences in their subjective impressions, trends in the behavioral and physiological data were also observed. Taken together, our results suggest that highly immersive systems could be further used for training in sports.
Safe Sex Education for Adolescent Daughters: vhaVenda Mothers Views

The study explored vhaVenda mothers' perceptions of imparting safe sex education to their adolescent daughters. Data was collected through six focus group discussions with each group consisting of six to eight mothers. The results indicated that mothers want their children to be knowledgeable about sexuality to avoid consequences associated with negative sexual behaviour. The mothers were of the vew that children ought to receive sexuality education from parents. Nonethless, relatively few parents appear to be eager to discuss sexuality in great depth.
Novel heterozygous C243Y A20/TNFAIP3 gene mutation is responsible for chronic inflammation in autosomal-dominant Behçet's disease

Objective Although Behçet's disease (BD) is a chronic inflammatory disorder of uncertain aetiology, the existence of familial BD with autosomal-dominant traits suggests that a responsibility gene (or genes) exists. We investigated a Japanese family with a history of BD to search for pathogenic mutations underlying the biological mechanisms of BD. Methods 6 patients over 4 generations who had suffered from frequent oral ulcers, genital ulcers and erythaema nodosum-like lesions in the skin were assessed. Whole-exome sequencing was performed on genomic DNA, and cytokine production was determined from stimulated mononuclear cells. Inflammatory cytokine secretion and Nod2-mediated NF-κB activation were analysed using the transfected cells. Results By whole-exome sequencing, we identified a common heterozygous missense mutation in A20/TNFAIP3, a gene known to regulate NF-κB signalling, for which all affected family members carried a heterozygous C243Y mutation in the ovarian tumour domain. Mononuclear cells obtained from the proband and his mother produced large amounts of interleukin 1β, IL-6 and tumour necrosis factor α (TNF-a) on stimulation as compared with those from normal controls. Although inflammatory cytokine secretion was suppressed by wild-type transfected cells, it was suppressed to a much lesser extent by mutated C243Y A20/TNFAIP3-transfected cells. In addition, impaired suppression of Nod2-mediated NF-κB activation by C243Y A20/TNFAIP3 was observed. Conclusions A C243Y mutation in A20/TNFAIP3 was likely responsible for increased production of human inflammatory cytokines by reduced suppression of NF-κB activation, and may have accounted for the autosomal-dominant Mendelian mode of BD transmission in this family.
Comparative Molecular Field Analysis Using Selectivity Fields Reveals Residues in the Third Transmembrane Helix of the Serotonin Transporter Associated with Substrate and Antagonist Recognition

The human serotonin transporter (hSERT) regulates the spatial and temporal actions of serotonin (5-HT) neurotransmission by removing 5-HT from the synapse. Previous studies have identified residues in the third transmembrane helix (TMH) that may be important for substrate translocation or antagonist recognition. We identified hSERT residues in TMH III that are divergent from Drosophila SERT and used species-scanning mutagenesis to generate reciprocal mutants. Transport inhibition assays suggest that the potency of substituted amphetamines was decreased for the hSERT mutants A169D, I172M, and S174M. In addition, there was a loss of potency for several antidepressants and 3-phenyltropane analogs for the I172M mutant. These results suggest that residues in TMH III may contribute to antagonist recognition. We carried out comparative molecular field analyses using selectivity fields to directly visualize the mutation-induced effects of antagonist potency for antidepressants, 3-phenyltropane analogs, and amphetamines. The hSERT I172M selectivity field analysis for the 3-phenyltropane analogs revealed that electrostatic interactions resulted in decreased potency. The amphetamine and antidepressant selectivity field analyses reveal the observed decreases in potencies for the hSERT I172M mutant are due to a change in tertiary structure of the hSERT protein and are not due to disruption of a direct binding site. Finally, the hSERT mutant A169D displayed altered kinetics for sodium binding, indicating that this residue may lie near the putative sodium binding site. A SERT homology model developed from the Aquifex aeolicus leucine transporter structure provides a structural context for further interpreting the results of the TMH III mutations.
A framework for quantitative security analysis of machine learning

We propose a framework for quantitative security analysis of machine learning methods. The key parts of this framework are the formal specification of a deployed learning model and attacker's constraints, the computation of an optimal attack, and the derivation of an upper bound on adversarial impact. We exemplarily apply the framework for the analysis of one specific learning scenario, online centroid anomaly detection, and experimentally verify the tightness of obtained theoretical bounds.
INVESTIGATING TEACHERS' PERCEIVED USE OF TEACHING AND LEARNING MATERIALS IN TEACHING CONTENT IN INCL

This study investigated teachers? perceived use of teaching and learning materials in inclusive classrooms. Based on the framework of Technological Pedagogical Content Knowledge (TPACK), the purpose is to determine teachers? perceived use of teaching and learning materials in the teaching of mathematics, social studies, science and literacy skills in inclusive basic schools. One hundred and forty-five participants were randomly surveyed from 35 inclusive pilot schools in Ghana. A (TPACK) instrument consisting of 47 items with Cronbach? s reliability coefficient; ranged from . 75- . 92 for the seven TPACK subscales were used for data collection. The Pearson correlation and t-test were used to analyze the data. The results revealed that there was a significant correlation between perceived use of TLM and TPACK variables. Significant differences were noted between male and female teachers? perceived use of TLM in mathematics and social studies. However, no difference was found in the use of TLM between the special educators and general educators. It was recommended that teacher education institutions should provide additional planning time for pre-service teachers to experiment with variety of teaching and learning materials in teaching mathematics, social studies, science, and literacy skills.
Opportunistic Relays in 802.11 Networks

We propose a new lightweight mechanism called Forwarding By Retransmission, that allows 802.11 stations to opportunistically relay overheard frames toward a destination. When a destination does not receive a frame, any other receiver that has better radio conditions than the source of the frame could participate in the retransmission process along with the source. This reduces the number of retransmissions made by stations with poor connectivity. We show by NS-2 simulations that our mechanism allows to fairly share the bandwidth among stations, even for those with poor radio quality and high packet error rates. Our solution comes with only a few modifications to the frame structure and a change in the acknowledgement semantic.
Perspectives on task ownership in mobile operating system development (invited talk)

There can be little contention about Stroustrup's epigrammatic remark: our civilization runs on software. However a caveat is increasingly due, much of the software that runs our civilization, runs on mobile devices today. Mobile operating systems have come to play a preeminent role in the ubiquity and utility of such devices. The development ecosystem of Android - one of the most popular mobile operating systems - presents an interesting context for studying whether and how collaboration dynamics in mobile development differ from conventional software development. In this paper, we examine factors that influence task ownership in Android development. Our results can inform project governance decisions at the individual and organizational levels.
Bayesian Exponential Family PCA

Principal Components Analysis (PCA) has become established as one of the key tools for dimensionality reduction when dealing with real valued data. Approaches such as exponential family PCA and non-negative matrix factorisation have successfully extended PCA to non-Gaussian data types, but these techniques fail to take advantage of Bayesian inference and can suffer from problems of over-fitting and poor generalisation. This paper presents a fully probabilistic approach to PCA, which is generalised to the exponential family, based on Hybrid Monte Carlo sampling. We describe the model which is based on a factorisation of the observed data matrix, and show performance of the model on both synthetic and real data.
Temperature Aware Task Scheduling in MPSoCs

In deep submicron circuits, elevation in temperatures has brought new challenges in reliability, timing, performance, cooling costs and leakage power. Conventional thermal management techniques sacrifice performance to control the thermal behavior by slowing down or turning off the processors when a critical temperature threshold is exceeded. Moreover, studies have shown that in addition to high temperatures, temporal and spatial variations in temperature impact system reliability. In this work, we explore the benefits of thermally aware task scheduling for multiprocessor systems-on-a-chip (MPSoC). We design and evaluate OS-level dynamic scheduling policies with negligible performance overhead. We show that, using simple to implement policies that make decisions based on temperature measurements, better temporal and spatial thermal profiles can be achieved in comparison to state-of-art schedulers. We also enhance reactive strategies such as dynamic thread migration with our scheduling policies. This way, hot spots and temperature variations are decreased, and the performance cost is significantly reduced
An Online Learning Method for Improving Over-Subscription Planning

Despite the recent resurgence of interest in learning methods for planning, most such efforts are still focused exclusively on classical planning problems. In this work, we investigate the effectiveness of learning approaches for improving over-subscription planning, a problem that has received significant recent interest. Viewing over-subscription planning as a domain-independent optimization problem, we adapt the STAGE (Boyan and Moore 2000) approach to learn and improve the plan search. The key challenge in our study is how to automate the feature generation process. In our case, we developed and experimented with a relational feature set, based on Taxonomic syntax as well as a propositional feature set, based on ground-facts. The feature generation process and training data generation process are all automatic, making it a completely domain-independent optimization process that takes advantage of online learning. In empirical studies, our proposed approach improved upon the baseline planner for over-subscription planning on many of the benchmark problems.
Learning Flexible Graph-Based Semi-Supervised Embedding

This paper introduces a graph-based semi-supervised embedding method as well as its kernelized version for generic classification and recognition tasks. The aim is to combine the merits of flexible manifold embedding and nonlinear graph-based embedding for semi-supervised learning. The proposed linear method will be flexible since it estimates a nonlinear manifold that is the closest one to a linear embedding. The proposed kernelized method will also be flexible since it estimates a kernel-based embedding that is the closest to a nonlinear manifold. In both proposed methods, the nonlinear manifold and the mapping (linear transform for the linear method and the kernel multipliers for the kernelized method) are simultaneously estimated, which overcomes the shortcomings of a cascaded estimation. The dimension of the final embedding obtained by the two proposed methods is not limited to the number of classes. They can be used by any kind of classifiers once the data are embedded into the new subspaces. Unlike nonlinear dimensionality reduction approaches, which suffer from out-of-sample problem, our proposed methods have an obvious advantage that the learnt subspace has a direct out-of-sample extension to novel samples, and are thus easily generalized to the entire high-dimensional input space. We provide extensive experiments on seven public databases in order to study the performance of the proposed methods. These experiments demonstrate much improvement over the state-of-the-art algorithms that are based on label propagation or graph-based semi-supervised embedding.
Frequency and spectrum of central nervous system involvement in 193 children with haemophagocytic lymphohistiocytosis

Haemophagocytic lymphohistiocytosis (HLH) may cause meningoencephalitis and significant neurological sequelae. We examined the relationship between neurological symptoms and cerebrospinal fluid (CSF) at diagnosis, and long‐term outcome, in all children enroled in the HLH‐94‐study prior to July 1, 2003, for whom information on CSF at diagnosis was available (n = 193). Patients were divided into four groups: (i) normal CSF (cells/protein) and no neurological symptoms (n = 71); (ii) normal CSF but neurological symptoms (n = 21); (iii) abnormal CSF but no symptoms (n = 50); and (iv) abnormal CSF with neurological symptoms (n = 51). At diagnosis, neurological symptoms were reported in 72/193 (37%) (seizures = 23); abnormal CSF in 101/193 (52%), and either or both in 122/193 (63%). Altogether 16/107 (15%) survivors had neurological sequelae at follow‐up (median 5·3 years). Multivariate hazard ratios (HR) for mortality were 0·98 [95% confidence interval (CI) = 0·42–2·31], 1·52 (0·82–2·82) and 2·05 (1·13–3·72) for groups 2–4, compared with group 1. Moreover, sequelae were more frequent in group 4 (7/21, 33%) compared to groups 1–3 (9/86, 10%) (P = 0·015). Patients with abnormal CSF at diagnosis had significantly increased mortality [HR = 1·78 (95% CI = 1·08–2·92), P = 0·023]. Thus, a substantial proportion of HLH survivors suffer neurological sequelae, and children with abnormal CSF have increased risk of mortality and neurological sequelae. Prompt treatment of HLH at onset or relapse may reduce these complications.
The Role of CDP-Diacylglycerol Synthetase and Phosphatidylinositol Synthase Activity Levels in the Regulation of Cellular Phosphatidylinositol Content*

The regulation of phosphatidylinositol synthesis was examined by cloning and expressing in COS-7 cells the human cDNAs encoding the two enzymes in the biosynthetic pathway. Human CDP-diacylglycerol synthetase (cds1) and phosphatidylinositol synthase (pis1) clones were identified in the human expressed sequence-tagged (EST) data base, and full-length cDNAs were obtained by library screening. The cds1 cDNA did not possess a recognizable mitochondrial import signal, and the activity of the expressed Cds1 protein was stimulated by nucleoside triphosphates in vitro, indicating that cds1 did not encode the mitochondrial-specific isozyme. There were two mRNA species (3.9 and 5.6 kilobases) detected on Northern blots hybridized with thecds1 probe that were expressed at distinctly different levels in various human tissues. Consistent with the presence of the two mRNAs, a cDNA predicted to encode a second human CDP-diacylglycerol synthetase (cds2) was also uncovered in the EST data base. In contrast to the two cds mRNAs, a single, 2.1-kilobase pis1 mRNA was uniformly expressed in all human tissues examined. Expression of the pis1 gene led to the overproduction of both phosphatidylinositol synthase and phosphatidylinositol:inositol exchange reactions, indicating that the Pis1 polypeptide catalyzed both of these activities. Phosphatase treatment of cell extracts abolished the CMP-independent phosphatidylinositol:inositol exchange reaction, and exchange activity was completely restored by the addition of CMP. Overexpression ofcds1 or pis1 alone or in combination did not enhance the rate of phosphatidylinositol biosynthesis. Also, overexpression did not result in a significant proportional increase in the cellular levels of CDP-diacylglycerol or phosphatidylinositol. These data illustrate that the levels of Cds1 and Pis1 protein expression are not critical determinants of cellular PtdIns content and argue against a determining role for the activity of either of these enzymes in the regulation of PtdIns biosynthesis.
Diversity of Flowering Responses in Wild Arabidopsis thaliana Strains

Although multiple environmental cues regulate the transition to flowering in Arabidopsis thaliana, previous studies have suggested that wild A. thaliana accessions fall primarily into two classes, distinguished by their requirement for vernalization (extended winter-like temperatures), which enables rapid flowering under long days. Much of the difference in vernalization response is apparently due to variation at two epistatically acting loci, FRI and FLC. We present the response of over 150 wild accessions to three different environmental variables. In long days, FLC is among those genes whose expression is most highly correlated with flowering. In short days, FRI and FLC are less important, although their contribution is still significant. In addition, there is considerable variation not only in vernalization response, but also in the response to differences in day length or ambient growth temperature. The identification of accessions that flower relatively early or late in specific environments suggests that many of the flowering-time pathways identified by mutagenesis, such as those that respond to day length, contribute to flowering-time variation in the wild. In contrast to differences in vernalization requirement, which are mainly mediated by FRI and FLC, it seems that variation in these other pathways is due to allelic effects at several different loci.
Real-time 3D echocardiographic quantification of left ventricular volumes: Multicenter study for validation with magnetic resonance imaging

Left ventricular (LV) volumes obtained from RT3DE datasets are underestimated compared to cardiac magnetic resonance (CMR). We sought to study the accuracy and reproducibility of this technique in a multicenter setting, the inter-institutional differences in these variables in relationship with investigatorspsila experience, and the potential sources of underestimation. 92 patients underwent CMR and RT3DE imaging at 4 different institutions. End-systolic and end-diastolic LV volumes correlated highly with CMR values (EDV: r=0.91; ESV: r=0.93), but were 29 and 26% lower. This finding was consistent across participating institutions, with the magnitude of bias being related to experience. Exclusion of trabeculae and mitral valve plane from the CMR reference essentially eliminated the inter-modality bias. In conclusion, LV volumes are underestimated in most patients because RT3DE imaging cannot differentiate between the myocardium and trabeculae.