Miracle-dz/UniFAR-FTUs huggingface dataset:
GWAS of DNA Methylation Variation Within Imprinting Control Regions Suggests Parent-of-Origin Association

Imprinting control regions (ICRs) play a fundamental role in establishing and maintaining the non-random monoallelic expression of certain genes, via common regulatory elements such as non-coding RNAs and differentially methylated regions (DMRs) of DNA. We recently surveyed DNA methylation levels within four ICRs (H19-ICR, IGF2-DMR, KvDMR, and NESPAS-ICR) in whole-blood genomic DNA from 128 monozygotic (MZ) and 128 dizygotic (DZ) human twin pairs. Our analyses revealed high individual variation and intra-domain covariation in methylation levels across CpGs and emphasized the interaction between epigenetic variation and the underlying genetic sequence in a parent-of-origin fashion. Here, we extend our analysis to conduct two genome-wide screenings of single nucleotide polymorphisms (SNPs) underlying either intra-domain covariation or parent-of-origin-dependent association with methylation status at individual CpG sites located within ICRs. Although genome-wide significance was not surpassed due to sample size limitations, the most significantly associated SNPs found through multiple-trait genome-wide association (MQFAM) included the previously described rs10732516, which is located in the vicinity of the H19-ICR. Similarly, we identified an association between rs965808 and methylation status within the NESPAS-ICR. This SNP is positioned within an intronic region of the overlapping genes GNAS and GNAS-AS1, which are imprinted genes regulated by the NESPAS-ICR. Sixteen other SNPs located in regions apart from the analyzed regions displayed suggestive association with intra-domain methylation. Additionally, we identified 13 SNPs displaying parent-of-origin association with individual methylation sites through family-based association testing. In this exploratory study, we show the value and feasibility of using alternative GWAS approaches in the study of the interaction between epigenetic state and genetic sequence within imprinting regulatory domains. Despite the relatively small sample size, we identified a number of SNPs displaying suggestive association either in a domain-wide or in a parent-of-origin fashion. Nevertheless, these associations will require future experimental validation or replication in larger and independent samples.
Leadership Skills of Gifted Students in a Rural Setting: Promising Programs for Leadership Development

As leadership abilities are used as one characteristic to identify giftedness, leadership skills should be an integral component of program services for gifted students. In one rural school district, a leadership training program was implemented to provide gifted education services. Gifted students in grades 10–12 volunteered to participate in a year-long program (i.e., Team Lead). Students were administered the Leadership Skills Inventory (Karnes & Chauvin, 2000) before the program began as a pre-assessment of their leadership skills. The inventory yielded scores in nine categories of leadership (i.e., fundamentals of leadership, written communication, speech communication, character- building, decision-making, group dynamics, problem solving, personal skills, and planning). Next, students participated in a book club, leadership activities, and the ropes training course. When administered the LSI as a post-assessment, the gifted students improved scores at a significant level from the pre-assessment.
[Clinical and cognitive predictors of psychosocial functioning during the euthymic period in bipolar disorder type II].

AIM Review of clinical and cognitive predictors of psychosocial functioning during the euthymic period in patients with bipolar disorder type II (BD II) was aimed in this paper. Psychosocial functioning status, clinical and cognitive predictors of psychosocial functioning and assessment of psychosocial functioning during the euthymic period in patients with BD-II were discussed. METHOD Studies investigated psychosocial functioning and its clinical and cognitive predictors were reviewed. Studies conducted between 1990 and 2013 were scanned. RESULTS It's been seen that there were limited studies investigating psychosocial functioning and predictors of psychosocial functioning. Findings from these limited studies indicated that patients with BD-II experienced psychosocial disability as much as BD-I did. It was reported that subclinical depressive symptoms and cognitive impairment were the prominent predictors of psychosocial functioning during the euthymic periods in patients with BD-II. CONCLUSION There are limited studies conducted in euthymic BD-II patients. There are various findings among the studies. Nevertheless, subclinical depressive symptoms and cognitive impairments are the prominent predictors of psychosocial functioning in euthymic BD-II patients. However, follow-up and cross-sectional studies are needed in this area.
Cell death of spinal cord ED1+ cells in a rat model of multiple sclerosis

Infiltration of macrophages into the central nervous system and activation of microglia are hallmarks of multiple sclerosis and its animal model—experimental autoimmune encephalomyelitis (EAE). Cell death in EAE has been demonstrated as an essential mechanism in the local regulation of the inflammatory reaction, but also as one of the major factors contributing to the destruction of the nervous tissue. The focus of this study was on detection of cell death among ED1+ cells (macrophages/activated microglia) in the spinal cord of Dark Agouti rats at the peak of EAE. Cell death was assessed using the TUNEL assay and immunostaining for cleaved caspase 3, as markers for cell death in general and “classical” apoptosis, respectively. Major infiltrates of immune cells were detected both in white matter and gray matter of spinal cords in rats at the disease peak. ED1, TUNEL, and caspase 3 positive cells were detected within, but also outside the infiltrates. There were more dying ED1+ cells in white matter than in gray matter, both in the general population and in infiltrated regions. The observed discrepancy in the proportion of dying ED1+ cells in spinal cord gray and white matter indicated that in EAE rat macrophages/microglia within gray matter are less prone to cell death induction. This is of special interest in the context of the increasingly appreciated contribution of spinal cord gray matter inflammation to multiple sclerosis pathogenesis. Our findings suggest that activated macrophages/microglia of gray matter are less susceptible to cell death induction. Alternatively, it can be assumed that intrinsic cell death-inductive mechanisms of nervous tissue differ in white and gray matter. Thus, further research on the gray matter macrophages/microglia cell death during EAE is warranted. They should be aimed at identification of the reasons for the observed differences and finding suitable ways to stimulate gray matter activated macrophages/microglia death.
IFITM Proteins Restrict Antibody-Dependent Enhancement of Dengue Virus Infection

Interferon-inducible transmembrane (IFITM) proteins restrict the entry processes of several pathogenic viruses, including the flaviviruses West Nile virus and dengue virus (DENV). DENV infects cells directly or via antibody-dependent enhancement (ADE) in Fc-receptor-bearing cells, a process thought to contribute to severe disease in a secondary infection. Here we investigated whether ADE-mediated DENV infection bypasses IFITM-mediated restriction or whether IFITM proteins can be protective in a secondary infection. We observed that IFITM proteins restricted ADE-mediated and direct infection with comparable efficiencies in a myelogenous leukemia cell line. Our data suggest that IFITM proteins can contribute to control of secondary DENV infections.
Rationality, Irrationality, and Wilf Equivalence in Generalized Factor Order

Let $P$ be a partially ordered set and consider the free monoid $P^{\ast}$ of all words over $P$. If $w,w' \in P^{\ast}$ then $w'$ is a factor of $w$ if there are words $u,v$ with $w=uw'v$. Define generalized factor order on $P^{\ast}$ by letting $u \leq w$ if there is a factor $w'$ of $w$ having the same length as $u$ such that $u \leq w'$, where the comparison of $u$ and $w'$ is done componentwise using the partial order in $P$. One obtains ordinary factor order by insisting that $u=w'$ or, equivalently, by taking $P$ to be an antichain. Given $u \in P^{\ast}$, we prove that the language $\mathcal{F}(u)=\{w : w \geq u\}$ is accepted by a finite state automaton. If $P$ is finite then it follows that the generating function $F(u)=\sum_{w \geq u} w$ is rational. This is an analogue of a theorem of Bjorner and Sagan for generalized subword order. We also consider $P=\mathbb{P}$, the positive integers with the usual total order, so that $\mathbb{P}^{\ast}$ is the set of compositions. In this case one obtains a weight generating function $F(u;t,x)$ by substituting $tx^n$ each time $n \in \mathbb{P}$ appears in $F(u)$. We show that this generating function is also rational by using the transfer-matrix method. Words $u,v$ are said to be Wilf equivalent if $F(u;t,x)=F(v;t,x)$ and we can prove various Wilf equivalences combinatorially. Bjorner found a recursive formula for the Mobius function of ordinary factor order on $P^{\ast}$. It follows that one always has $\mu (u,w)=0, \pm 1$. Using the Pumping Lemma we show that the generating function $M(u)= \sum_{w \geq u} | \mu (u,w) | w$ can be irrational.
High Concentrations of Methyl Fluoride Affect the Bacterial Community in a Thermophilic Methanogenic Sludge

To precisely control the application of methyl fluoride (CH3F) for analysis of methanogenic pathways, the influence of 0–10% CH3F on bacterial and archaeal communities in a thermophilic methanogenic sludge was investigated. The results suggested that CH3F acts specifically on acetoclastic methanogenesis. The inhibitory effect stabilized at an initial concentration of 3–5%, with around 90% of the total methanogenic activity being suppressed, and a characteristic of hydrogenotrophic pathway in isotope fractionation was demonstrated under this condition. However, extended exposure (12 days) to high concentrations of CH3F (>3%) altered the bacterial community structure significantly, resulting in increased diversity and decreased evenness, which can be related to acetate oxidation and CH3F degradation. Bacterial clone library analysis showed that syntrophic acetate oxidizing bacteria Thermacetogenium phaeum were highly enriched under the suppression of 10% CH3F. However, the methanogenic community did not change obviously. Thus, excessive usage of CH3F over the long term can change the composition of the bacterial community. Therefore, data from studies involving the use of CH3F as an acetoclast inhibitor should be interpreted with care. Conversely, CH3F has been suggested as a factor to stimulate the enrichment of syntrophic acetate oxidizing bacteria.
Pharmacokinetic Study of Adjuvant Gemcitabine Therapy for Biliary Tract Cancer following Major Hepatectomy (KHBO1101)

Background Biliary tract cancer (BTC) patients who have undergone surgical resection with major hepatectomy cannot tolerate the standard gemcitabine regimen (1,000 mg/m2 on days 1, 8, and 15 every 4 weeks) due to severe toxicities such as myelosuppression. Our dose-finding study of adjuvant gemcitabine therapy for biliary tract cancer following major hepatectomy determined that the recommended dose is 1,000 mg/m2 on days 1 and 15 every 4 weeks. Here, we evaluate the pharmacokinetics and pharmacodynamics of gemcitabine in these subjects. Methods We evaluated BTC patients scheduled to undergo surgical resection with major hepatectomy followed by gemcitabine therapy. A pharmacokinetic evaluation of gemcitabine and its main metabolite, 2′,2′-difluorodeoxyuridine (dFdU), was conducted at the initial administration of gemcitabine, which was given by intravenous infusion over 30 min at a dose of 800–1,000 mg/m2. Physical examination and adverse events were monitored for 12 weeks. Results Thirteen patients were enrolled from August 2011 to January 2013, with 12 ultimately completing the pharmacokinetic study. Eight patients had hilar cholangiocarcinoma, three had intrahepatic cholangiocarcinoma, and one had superficial spreading type cholangiocarcinoma. The median interval from surgery to first administration of gemcitabine was 65.5 days (range, 43–83 days). We observed the following toxicities: neutropenia (n = 11, 91.7%), leukopenia (n = 10, 83.3%), thrombocytopenia (n = 6, 50.0%), and infection (n = 5, 41.7%). Grade 3 or 4 neutropenia was observed in 25% (n = 3) of patients. There were differences in clearance of gemcitabine and dFdU between our subjects and the subjects who had not undergone hepatectomy. Conclusion Major hepatectomy did not affect the pharmacokinetics of gemcitabine or dFdU. Trial Registration UMIN-CTR in (JPRN) UMIN000005109
Brain Volume in Autism

Increased brain size has been observed in individuals with autism with a wide range of cognitive functioning. The purpose of this investigation was to obtain measurements of the brain volume in a sample of nonmentally retarded autistic individuals. Magnetic resonance imaging scans from 16 nonmentally retarded individuals with autism and 19 male volunteer comparison subjects were obtained and the following structures were measured: third, fourth, and lateral ventricles and intracranial and cerebral volumes. Mean cerebral and third ventricle volumes in the autistic subjects were significantly greater than in the controls when adjusted for intracranial volume. No other significant results were found. Our finding of increased brain volume in autism is consistent with previous reports in the literature. Additional longitudinal neuroimaging and, more importantly, neuropathologic studies are warranted to provide a better understanding of the complexities underlying increased brain size in autism. (J Child Neurol 2001;16:421-424).
Ventriculoperitoneal shunt block: what are the best predictive clinical indicators?

Aims: To evaluate the predictive value of symptoms, signs, and radiographic findings accompanying presumed ventriculoperitoneal (VP) shunt malfunction, by comparing presentation with operative findings and subsequent clinical course. Methods: Prospective study of all 53 patient referrals to a paediatric neurosurgical centre between April and November 1999 with a diagnosis of presumed shunt malfunction. Referral pattern, presenting symptoms and signs, results of computed tomography (CT) scanning, operative findings, and clinical outcome were recorded. Two patient groups were defined, one with proven shunt block, the other with presumed normal shunt function. Symptomatology, CT scan findings, and the subsequent clinical course for each group were then compared. Results: Common presenting features were headache, drowsiness, and vomiting. CT scans were performed in all patients. Thirty seven had operatively proven shunt malfunction, of whom 34 had shunt block and three shunt infection; 84% with shunt block had increased ventricle size when compared with previous imaging. For the two patient groups (with and without shunt block), odds ratios with 95% confidence intervals on their presenting symptoms were headache 1.5 (0.27 to 10.9), vomiting 0.9 (0.25 to 3.65), drowsiness 10 (0.69 to 10.7), and fever 0.19 (0.03 to 6.95). Every patient with ventricular enlargement greater than their known baseline had a proven blocked shunt. Conclusions: Drowsiness is by far the best clinical predictor of VP shunt block. Headache and vomiting were less predictive of acute shunt block in this study. Wherever possible CT scan findings should be interpreted in the context of previous imaging. We would caution that not all cases of proven shunt blockage present with an increase in ventricle size.
Objective evaluation of binocular function using the pattern reversal visual evoked response. II. Effect of mean luminosity

Abstract The effect of mean luminosity change on pattern reversal visual evoked response (VER), especially monocular VER, binocular VER and binocular summation, was studied. The mean luminosity level was changed with the use of neutral density filters. When mean luminosity level was decreased binocularly, binocular and monocular VER amplitudes decreased and binocular summation increased, reaching its peak at a luminosity of ‐0.3 log foot‐lambert. When mean luminosity was changed monocularly and the interocular luminosity difference was larger than 0.6 log unit, the binocular VER became almost equal to or smaller than the monocular VER. In dim luminosity, the binocular system functioned better than the monocular system. Even a slight luminositv difference between the two eyes could disturb the binocular system.
Use of Donkey Milk in Children with Cow’s Milk Protein Allergy

Human breast milk is the best nutritional support that insures the right development and influences the immune status of the newborn infant. However, when it is not possible to breast feed, it may be necessary to use commercial infant formulas that mimic, where possible, the levels and types of nutrients present in human milk. Despite this, some formula-fed infant develops allergy and/or atopic disease compared to breast-fed infants. Cow’s milk allergy can be divided into immunoglobulin IgE mediated food allergy and non-IgE-mediated food allergy. Most infants with cow’s milk protein allergy (CMPA) develop symptoms before 1 month of age, often within 1 week after introduction of cow’s milk-based formula. Donkey milk may be considered a good substitute for cow’s milk in feeding children with CMPA since its composition is very similar to human milk. Donkey milk total protein content is low (1.5–1.8 g/100 g), very close to human milk. A thorough analysis of the donkey milk protein profile has been performed in this study; the interest was focused on the milk proteins considered safe for the prevention and treatment of various disorders in humans. The content of lactoferrin, lactoperoxidase and lysozyme, peptides with antimicrobial activity, able to stimulate the development of the neonatal intestine, was determined. Donkey milk is characterized by a low casein content, with values very close to human milk; the total whey protein content in donkey milk ranges between 0.49 and 0.80 g/100 g, very close to human milk (0.68–0.83 g/100 g). Among whey proteins, α-lactalbumin average concentration in donkey milk is 1.8 mg/mL. The results of this study confirmed the possibility of using donkey milk in feeding children with CMPA.
Collective Self-Verification Among Members of a Naturally Occurring Group: Possible Antecedents and Long-Term Consequences

Extending prior work on collective self-verification (e.g., Chen, Chen, & Shaw, 2004), the present study examined possible antecedents and long-term correlates of collective self-verification among members of a naturally occurring group. Group members were randomly paired and collective self-verification was assessed in terms of the degree of correspondence between ratings of the self as a group member and partners' ratings of the self as a member. Greater correspondence in self- and partner ratings was found for attributes that group members idiographically deemed highly central to defining the group relative to their idiographic, low-centrality attributes. Moreover, this attribute centrality effect was particularly apparent among highly identified group members. Finally, self–partner correspondence was positively associated with participants' perceptions of themselves as prototypical group members and their dedication to the group, both assessed months later.
The YATE fail-safe interface: the user's point of view

This paper deals with some aspects of the use of self-checking integrated circuits in an application that manages the major risks involved in a transport system. It aims to provide an objective account of the advantages and disadvantages of this type of technology. Attention has been focused on the demands made by such integrated circuits on their environment, in particular the CPUs which control them. Nevertheless, much work still needs to be done to bring the design and testing of integrated circuits more in line with the needs of rail safely applications.
Lazy database replication with snapshot isolation

Snapshot isolation is a popular transactional isolation level in database systems. Several replication techniques based on snapshot isolation have recently been proposed. These proposals, however, do not fully leverage the local concurrency controls that provide snapshot isolation. Furthermore, guaranteeing snapshot isolation in lazy replicated systems may result in transaction inversions, which happen when transactions see stale data. Strong snapshot isolation, which is provided in centralized database servers, avoids transaction inversions but is expensive to provide in a lazy replicated system. In this paper, we show how snapshot isolation can be maintained in lazy replicated systems while taking full advantage of the local concurrency controls. We propose strong session snapshot isolation, a correctness criterion that prevents transaction inversions. We show how strong session snapshot isolation can be implemented efficiently in a lazy replicated database system. Through performance studies, we quantify the cost of implementing our techniques in lazy replicated systems.
A Congestion-aware Medium Access Control Protocol for Multi-rate Ad-hoc Networks

This paper investigates the problem of how to improve TCP performance in multi-rate ad-hoc networks with congested links. To improve network performance, different rate adaptation algorithms, such as automatic rate fallback (ARF) and receiver-based autorate (RBAR), have been proposed to adapt the data rate according to the current channel quality. Opportunistic auto rate (OAR) protocol is an optimisation for any existing rate adaptation algorithm which leads to a significant performance gain by providing temporal fairness. We analyze the reasons for the high performance gain obtained using OAR, and show that the OAR protocol does not work well for TCP communications in ad-hoc networks where nodes use different data rates to communicate with each other (heterogeneous). Based on these analysis, we propose a congestion reactive opportunistic auto rate (CROAR) protocol, which is a new rate adaption enhancement tailored to improve TCP performance in heterogeneous multi-hop ad-hoc networks. Extensive simulations show that CROAR, compared to OAR and RBAR, produces significant throughput and end-to-end transmission latency improvements while only marginally relaxing temporal fairness