Miracle-dz/UniFAR-FTUs huggingface dataset:
Histone variant macroH2A marks embryonic differentiation in vivo and acts as an epigenetic barrier to induced pluripotency

Summary How cell fate becomes restricted during somatic cell differentiation is a long-lasting question in biology. Epigenetic mechanisms not present in pluripotent cells and acquired during embryonic development are expected to stabilize the differentiated state of somatic cells and thereby restrict their ability to convert to another fate. The histone variant macroH2A acts as a component of an epigenetic multilayer that heritably maintains the silent X chromosome and has been shown to restrict tumor development. Here we show that macroH2A marks the differentiated cell state during mouse embryogenesis. MacroH2A.1 was found to be present at low levels upon the establishment of pluripotency in the inner cell mass and epiblast, but it was highly enriched in the trophectoderm and differentiated somatic cells later in mouse development. Chromatin immunoprecipitation revealed that macroH2A.1 is incorporated in the chromatin of regulatory regions of pluripotency genes in somatic cells such as mouse embryonic fibroblasts and adult neural stem cells, but not in embryonic stem cells. Removal of macroH2A.1, macroH2A.2 or both increased the efficiency of induced pluripotency up to 25-fold. The obtained induced pluripotent stem cells reactivated pluripotency genes, silenced retroviral transgenes and contributed to chimeras. In addition, overexpression of macroH2A isoforms prevented efficient reprogramming of epiblast stem cells to naïve pluripotency. In summary, our study identifies for the first time a link between an epigenetic mark and cell fate restriction during somatic cell differentiation, which helps to maintain cell identity and antagonizes induction of a pluripotent stem cell state.
Constraint Reduction using Marginal Polytope Diagrams for MAP LP Relaxations

LP relaxation-based message passing algorithms provide an effective tool for MAP inference over Probabilistic Graphical Models. However, different LP relaxations often have different objective functions and variables of differing dimensions, which presents a barrier to effective comparison and analysis. In addition, the computational complexity of LP relaxation-based methods grows quickly with the number of constraints. Reducing the number of constraints without sacrificing the quality of the solutions is thus desirable. We propose a unified formulation under which existing MAP LP relaxations may be compared and analysed. Furthermore, we propose a new tool called Marginal Polytope Diagrams. Some properties of Marginal Polytope Diagrams are exploited such as node redundancy and edge equivalence. We show that using Marginal Polytope Diagrams allows the number of constraints to be reduced without loosening the LP relaxations. Then, using Marginal Polytope Diagrams and constraint reduction, we develop three novel message passing algorithms, and demonstrate that two of these show a significant improvement in speed over state-of-art algorithms while delivering a competitive, and sometimes higher, quality of solution.
University teachers’ self-reflection on their academic growth

This study followed the academic growth of four university teachers, over a two-year period, with the intention of enhancing inquiry-based learning in practice. Data were generated within the natural settings of classrooms, laboratories and lecture halls, through the analysis of teaching materials, low-participation observation, informal discussions and semi-formal interviews. The research approach was based on a critical social paradigm, assuming principles of action-research methodology privileging a transitional ‘instructional coaching approach’. Outcomes show a marked interest in the design and development of innovative approaches to teaching, learning, feedback and assessment. They demonstrated strong collaborative practices, insightful reflections on their teaching activities, and willingness to share evaluations both within and without of university contexts and successfully contributing thoughts and ideas to a wider audience.
estimating premorbid WAIS-R IQ with demographic variables: Regression equations derived from a UK sample

Abstract A sample of 200 healthy individuals, representative of the adult UK population in terms of age, gender, and occupational classification, completed a full-length WAIS-R. Demographic variables for the participants were recorded (age, gender, years of education, and occupational classification) and used to develop regression equations for the estimation of premorbid WAIS-R IQ. Stepwise multiple regression revealed that occupation was the best predictor of IQ for all three WAIS-R scales (FSIQ, VIQ, and PIQ). Age and years of education significantly increased the variance predicted. Together these three variables accounted for 53%, 53%, and 32% of the variance in FSIQ, VIQ, and PIQ, respectively. The results indicated that the demographic approach to the estimation of premorbid WAIS-R IQ has utility beyond the USA. However, in common with findings for American participants (Barona, Reynolds, & Chastain, 1984) the ability to predict PIQ was markedly inferior to that achieved for FSIQ and VIQ. A frequen.
Effects of Grazing and Precipitation on Herbage Biomass, Herbage Nutritive Value, and Yak Performance in an Alpine Meadow on the Qinghai–Tibetan Plateau

The Qinghai–Tibetan Plateau is a very large land unit and an important terrestrial ecosystem within the Eurasian continent. Because of the harsh climate associated with the high altitude, alpine meadows on the plateau are susceptible to degradation from overgrazing. For this region, and for other alpine meadow pastures internationally, there is a need to define the sustainable stocking rate, to develop sound policy pertaining to future land use. Here we report biomass and liveweight gain per animal and per ha for pastures grazed by yaks at high, medium, or low stocking rates over 4 growing seasons from 2010 to 2013. Measures of herbage nutritive value are reported. The influence of inter-year variation in precipitation on standing herbage biomass was also evaluated. Higher precipitation increased standing herbage biomass and herbage nutritive value, indicating that vegetation suffered summer water deficit even in this environment. The sustainable stocking rate in this environment was determined to be approximately 1 yak ha-1 (grown from 80 kg to 120 kg liveweight in 90 d). At this stocking rate, yak weight gain per ha was 88% of that achieved at higher stocking rates typically used by farmers, but with little or no evidence of land degradation.
Prevalence of Vestibular Disorder in Older People Who Experience Dizziness

Dizziness and imbalance are clinically poorly defined terms, which affect ~30% of people over 65 years of age. In these people, it is often difficult to define the primary cause of dizziness, as it can stem from cardiovascular, vestibular, psychological, and neuromuscular causes. However, identification of the primary cause is vital in determining the most effective treatment strategy for a patient. Our aim is to accurately identify the prevalence of benign paroxysmal positional vertigo (BPPV), peripheral, and central vestibular hypofunction in people aged over 50 years who had experienced dizziness within the past year. Seventy-six participants aged 51–92 (mean ± SD = 69 ± 9.5 years) were tested using the head thrust dynamic visual acuity (htDVA) test, dizziness handicap inventory (DHI), as well as sinusoidal and unidirectional rotational chair testing, in order to obtain data for htDVA score, DHI score, sinusoidal (whole-body, 0.1–2 Hz with peak velocity at 30°/s) vestibulo-ocular reflex (VOR) gain and phase, transient (whole-body, acceleration at 150°/s2 to a constant velocity rotation of 50°/s) VOR gain and time constant (TC), optokinetic nystagmus (OKN) gain, and TC (whole-body, constant velocity rotation at 50°/s). We found that BPPV, peripheral and central vestibular hypofunction were present in 38 and 1% of participants, respectively, suggesting a likely vestibular cause of dizziness in these people. Of those with a likely vestibular cause, 63% had BPPV; a figure higher than previously reported in dizziness clinics of ~25%. Our results indicate that htDVA, sinusoidal (particularly 0.5–1 Hz), and transient VOR testing were the most effective at detecting people with BPPV or vestibular hypofunction, whereas DHI and OKN were effective at only detecting non-BPPV vestibular hypofunction.
Characterization of Symmetric Complexes of Nerve Growth Factor and the Ectodomain of the Pan-neurotrophin Receptor, p75NTR*

Nerve growth factor (NGF) is the ligand for two unrelated cellular receptors, TrkA and p75NTR, and acts as a mediator in the development and maintenance of the mammalian nervous system. Signaling through TrkA kinase domains promotes neuronal survival, whereas activation of the p75NTR “death domains” induces apoptosis under correct physiological conditions. However, co-expression of these receptors leads to enhanced neuronal survival upon NGF stimulation, possibly through a ternary p75NTR·NGF·TrkA complex. We have expressed human p75NTR ligand binding domain as a secreted glycosylated protein in Trichoplusia ni cells. Following assembly and purification of soluble p75NTR·NGF complexes, mass spectrometry, analytical ultracentrifugation, and solution x-ray scattering measurements are indicative of 2:2 stoichiometry, which implies a symmetric complex. Molecular models of the 2:2 p75NTR·NGF complex based on these data are not consistent with the further assembly of either symmetric (2:2:2) or asymmetric (2:2:1) ternary p75NTR·NGF·TrkA complexes.
Comorbidity and Functional Trajectories From Midlife to Old Age: The Health and Retirement Study

Background. The number of diseases and physical functioning difficulties tend to increase with age. The aim of this study was to examine the trajectories of physical functioning across age groups and whether the trajectories differ according to disease status in different population subgroups. Methods. Repeat data from a nationally representative population sample, the Health and Retirement Study, was used. Participants were 10,709 men and 13,477 women aged 60–107 years at baseline with biennial surveys from 1992 to 2010. Average length of follow-up was 10.3 years ranging from 0 to 18 years. Disease status and physical functioning was asked about at all study phases and 10 items were summed to obtain a physical functioning score (0–10). Results. Age modified the relationship between number of chronic diseases and physical functioning with older participants having more physical functioning difficulties with increasing number of diseases. An average 70-year-old participant with no diseases had 0.89 (95% CI: 0.85–0.93) physical functioning difficulties, with one disease 1.72 (95% CI: 1.69–1.76) difficulties, with two diseases 2.57 (95% CI: 2.52–2.62) difficulties, and with three or more diseases 3.82 (95% CI: 3.76–3.88) difficulties. Of the individual diseases memory-related diseases, stroke, pulmonary diseases, and arthritis were associated with significantly higher physical functioning difficulties compared with other diseases. Conclusions. Comorbidity is associated with greater burden of physical functioning difficulties. Of the studied diseases, memory-related diseases, stroke, pulmonary diseases, and arthritis alone or in combination limit most physical functioning.
Formation of algorithms module and dynamic interface in web mining and storage process to retrieve metadata

Web system technology is rapidly used by most of the users and there has been a speedy change in the technology to access the information in past fifteen years and at the same time it is highly recommended to cope up with the existing and emerging technologies. Metadata are integral part of information and at the same time it is very important to enhance metadata. It is highly recommended that efficient information retrieval is the most basic need of any kind of user. Efficient set of information is called the significant document which has efficient storage, effective extraction along with the free from different kinds of error. The study of this research paper is to develop an algorithm for storage of metadata to reduce the complexity of storage algorithm for efficient retrieval of web documents in web system so that user can get efficient retrieval of information in distributed environment. This study aims to provide a framework for efficient collection of metadata in distributed environment to improve the web mining for users. Concerning of knowledge issues on web using different kind of methodologies, this study provides the important information.
Do the ends justify the mean? Proline mutations at the ends of the keratin coiled-coil rod segment are more disruptive than internal mutations

Intermediate filament (IF) assembly is remarkable, in that it appears to be self-driven by the primary sequence of IF proteins, a family (40- 220 kd) with diverse sequences, but similar secondary structures. Each IF polypeptide has a central 310 amino acid residue alpha-helical rod domain, involved in coiled-coil dinner formation. Two short (approximately 10 amino acid residue) stretches at the ends of this rod are more highly conserved than the rest, although the molecular basis for this is unknown. In addition, the rod is segmented by three short nonhelical linkers of conserved location, but not sequence. To examine the degree to which different conserved helical and nonhelical rod sequences contribute to dimer, tetramer, and higher ordered interactions, we introduced proline mutations in residues throughout the rod of a type I keratin, and we removed existing proline residues from the linker regions. To further probe the role of the rod ends, we introduced more subtle mutations near the COOH-terminus. We examined the consequences of these mutations on (a) IF network formation in vivo, and (b) 10-nm filament assembly in vitro. Surprisingly, all proline mutations located deep in the coiled-coil rod segment showed rather modest effects on filament network formation and 10-nm filament assembly. In addition, removing the existing proline residues was without apparent effect in vivo, and in vitro, these mutants assembled into 10-nm filaments with a tendency to aggregate, but with otherwise normal appearance. The most striking effects on filament network formation and IF assembly were observed with mutations at the very ends of the rod. These data indicate that sequences throughout the rod are not equal with respect to their role in filament network formation and in 10-nm filament assembly. Specifically, while the internal rod segments seem able to tolerate considerable changes in alpha-helical conformation, the conserved ends seem to be essential for creating a very specific structure, in which even small perturbations can lead to loss of IF stability and disruption of normal cellular interactions. These findings have important implications for the disease Epidermolysis Bullosa Simplex, arising from point mutations in keratins K5 or K14.
The Mechanism of Environmental Endocrine Disruptors (DEHP) Induces Epigenetic Transgenerational Inheritance of Cryptorchidism

Discussion on the role of DEHP in the critical period of gonadal development in pregnant rats (F0), studied the evolution of F1-F4 generation of inter-generational inheritance of cryptorchidism and the alteration of DNA methylation levels in testis. Pregnant SD rats were randomly divided into two groups: normal control group and DEHP experimental group. From pregnancy 7d to 19d, experimental group was sustained to gavage DEHP 750mg/kg bw/day, observed the incidence of cryptorchidism in offspring and examined the pregnancy rate of female rats through mating experiments. Continuous recording the rat’s weight and AGD value, after maturation (PND80) recording testis and epididymis’ size and weight, detected the sperm number and quality. Subsequently, we examined the evolution morphological changes of testicular tissue for 4 generation rats by HE staining and Western Blot. Completed the MeDIP-sequencing analysis of 6 samples (F1 generation, F4 generation and Control). DEHP successfully induced cryptorchidism occurrence in offspring during pregnancy. The incidence of cryptorchidism in F1 was 30%, in F2 was 12.5%, and there was no cryptorchidism coming up in F3 and F4. Mating experiment shows conception rate 50% in F1, F2 generation was 75%, the F3 and F4 generation were 100%. HE staining showed that the seminiferous epithelium of F1 generation was atrophy and with a few spermatogenic cell, F2 generation had improved, F3 and F4 generation were tend to be normal. The DNA methyltransferase expression was up-regulated with the increase of generations by Real Time-PCR, immunohistochemistry and Western Blot. MeDIP-seq Data Analysis Results show many differentially methylated DNA sequences between F1 and F4. DEHP damage male reproductive function in rats, affect expression of DNA methyltransferase enzyme, which in turn leads to genomic imprinting methylation pattern changes and passed on to the next generation, so that the offspring of male reproductive system critical role in the development of imprinted genes imbalances, and eventually lead to producing offspring cryptorchidism. This may be an important mechanism of reproductive system damage.
Pilot Decontamination in Noncooperative Massive MIMO Cellular Networks Based on Spatial Filtering

Pilot contamination has been known as one of the most challenging issues in massive multiple-input multiple-output (MIMO) systems. Every user will experience interferences from users in adjacent cells who employ the same pilot sequence. For cell-edge users, pilot contamination is particularly detrimental, because their signals might be overwhelmed by the interference. In this paper, we propose a pilot decontamination method based on a spatial filter, which exploits the spatial sparsity of massive MIMO channels. In massive MIMO systems, the communication protocols are generally divided into four phases: pilot transmission, processing, uplink data transmission, and downlink data transmission. In the first phase, the base station (BS) receives both the desired signal and the pilot contaminated signal. In the second phase, all users in the target cell stay silent for one symbol period, and the BS only receives interference from adjacent cells. The fast Fourier transform can then be employed to analyze the spatial spectrums of the received signals. The spatial sparsity of the massive MIMO channels makes it possible to identify the pilot contamination components by comparing the two spectrums on different spatial signatures (or angles of arrival). A spatial filter can then be constructed to eliminate pilot contamination. Both the theoretical analysis and simulation results demonstrate the effectiveness of the proposed method, whose complexity is comparable to that of the traditional matched filter-based channel estimator.
Reinforcement Matching Using Region Context

Local feature-based matching is robust to both clutter and occlusion. However, a primary shortcoming of local features is a deficiency of global information that can cause ambiguities in matching. Local features combined with global relationships convey much more information, but global spatial information is often not robust to occlusion and/or non-rigid transformations. This paper proposes a new framework for including global context information into local feature matching, while still maintaining robustness to occlusion, clutter, and nonrigid transformations. To generate global context information, we extend previous fixed-scale, circular-bin methods by using affine-invariant log-polar elliptical bins. Further, we employ a reinforcement matching scheme that provides greater robustness to occlusion and clutter than previous methods that non-discriminately compare accumulated bins values over the entire context. We also present a more robust method of calculating a feature’s dominant orientation. We compare reinforcement matching to nearest neighbor matching without region context and to robust matching methods (RANSAC and PROSAC).
Hyaluronic Acid Levels Predict Risk of Hepatic Encephalopathy and Liver-Related Death in HIV/Viral Hepatitis Coinfected Patients

Background Whereas it is well established that various soluble biomarkers can predict level of liver fibrosis, their ability to predict liver-related clinical outcomes is less clearly established, in particular among HIV/viral hepatitis co-infected persons. We investigated plasma hyaluronic acid’s (HA) ability to predict risk of liver-related events (LRE; hepatic coma or liver-related death) in the EuroSIDA study. Methods Patients included were positive for anti-HCV and/or HBsAg with at least one available plasma sample. The earliest collected plasma sample was tested for HA (normal range 0–75 ng/mL) and levels were associated with risk of LRE. Change in HA per year of follow-up was estimated after measuring HA levels in latest sample before the LRE for those experiencing this outcome (cases) and in a random selection of one sixth of the remaining patients (controls). Results During a median of 8.2 years of follow-up, 84/1252 (6.7%) patients developed a LRE. Baseline median (IQR) HA in those without and with a LRE was 31.8 (17.2–62.6) and 221.6 ng/mL (74.9–611.3), respectively (p<0.0001). After adjustment, HA levels predicted risk of contracting a LRE; incidence rate ratios for HA levels 75–250 or ≥250 vs. <75 ng/mL were 5.22 (95% CI 2.86–9.26, p<0.0007) and 28.22 (95% CI 14.95–46.00, p<0.0001), respectively. Median HA levels increased substantially prior to developing a LRE (107.6 ng/mL, IQR 0.8 to 251.1), but remained stable for controls (1.0 ng/mL, IQR –5.1 to 8.2), (p<0.0001 comparing cases and controls), and greater increases predicted risk of a LRE in adjusted models (p<0.001). Conclusions An elevated level of plasma HA, particularly if the level further increases over time, substantially increases the risk of contracting LRE over the next five years. HA is an inexpensive, standardized and non-invasive supplement to other methods aimed at identifying HIV/viral hepatitis co-infected patients at risk of hepatic complications.
PTSD symptoms, response to intrusive memories and coping in ambulance service workers.

OBJECTIVES To examine the relationship of coping strategies and responses to intrusive memories with post-traumatic stress disorder (PTSD) and other psychiatric symptoms in ambulance service workers. METHOD Fifty-six ambulance service workers describe the most distressing aspects of their work and completed questionnaires designed to measure their coping strategies in dealing with distressing incidents. They also described their intrusive memories of particularly distressing incidents and completed a questionnaire designed to measure their interpretation of these intrusions and their responses to them. In addition, they completed the Post-traumatic Stress Symptom Scale (PSS; Foa, Riggs, Dancu & Rothbaum, 1993) and the General Health Questionnaire (GHQ; Goldberg & Hiller, 1979). RESULTS Of the participants, 21% met DSM-III-R criteria for PTSD, and 22% met GHQ screening criteria for psychiatric symptoms. Wishful thinking and mental disengagement when confronted with critical incidents at work, negative interpretations of intrusive memories, and maladaptive responses to these memories (rumination, suppression and dissociation) correlated with PTSD severity. CONCLUSION The results are consistent with the hypothesis that coping strategies and responses to intrusive memories that prevent emotional processing of the distressing event maintain PTSD. They also support Ehlers & Steil's (1995) hypotheses about the role of negative interpretations of post-traumatic intrusions in PTSD. A substantial subgroup of emergency service personnel may need support in processing distressing incidents at work and may benefit from information that normalizes post-traumatic symptoms such as intrusions.