Miracle-dz/UniFAR-FTUs huggingface dataset:
H 3 K 4 demethylase KDM 5 B regulates global dynamics of transcription elongation and alternative splicing in embryonic stem cells

Epigenetic regulation of chromatin plays a critical role in controlling embryonic stem (ES) cell selfrenewal and pluripotency. However, the roles of histone demethylases and activating histone modifications such as trimethylated histone 3 lysine 4 (H3K4me3) in transcriptional events such as RNA polymerase II (RNAPII) elongation and alternative splicing are largely unknown. In this study, we show that KDM5B, which demethylates H3K4me3, plays an integral role in regulating RNAPII occupancy, transcriptional initiation and elongation, and alternative splicing events in ES cells. Depletion of KDM5B leads to altered RNAPII promoter occupancy, and decreased RNAPII initiation and elongation rates at active genes and at genes marked with broad H3K4me3 domains. Moreover, our results demonstrate that spreading of H3K4me3 from promoter to gene body regions, which is mediated by depletion of KDM5B, modulates RNAPII elongation rates and RNA splicing in ES cells. We further show that KDM5B is enriched nearby alternatively spliced exons, and depletion of KDM5B leads to altered levels of H3K4 methylation in alternatively spliced exon regions, which is accompanied by differential expression of these alternatively splice exons. Altogether, our data indicate an epigenetic role for KDM5B in regulating RNAPII elongation and alternative splicing, which may support the diverse mRNA repertoire in ES cells.
Perceived social support and mortality in older people.

OBJECTIVES This study examines the effect of perceived social support on all-cause mortality at a 10-year follow-up as well as the plausible mediating factors in this association. METHODS We measured perceived social support in 206 Finnish men and women aged 80 years old by using the Social Provision Scale, which consists of six dimensions: attachment, social integration, opportunity for nurturance, reassurance of worth, reliable alliance, and guidance. RESULTS By using a theoretical framework that divided perceived social support into assistance-related and non-assistance-related support, we found that the risk of death was almost 2.5 times higher in women in the lowest tertile of non-assistance-related social support (comprising infrequent experiences of reassurance of worth, emotional closeness, sense of belonging and opportunity for nurturance) than in women in the highest tertile. The risk remained strong even when we controlled for the indicators of baseline sociodemographics and psychological and physiological health and functioning. Among men, none of the perceived social support dimensions showed a significant association with mortality. DISCUSSION The results of this study present a challenge for society to find and develop new social innovations and interventions in order to promote a sense of emotional social support in older people, thereby contributing to their health and welfare.
α‐helix stabilization by alanine relative to glycine: Roles of polar and apolar solvent exposures and of backbone entropy

The energetics of α‐helix formation are fairly well understood and the helix content of a given amino acid sequence can be calculated with reasonable accuracy from helix‐coil transition theories that assign to the different residues specific effects on helix stability. In internal helical positions, alanine is regarded as the most stabilizing residue, whereas glycine, after proline, is the more destabilizing. The difference in stabilization afforded by alanine and glycine has been explained by invoking various physical reasons, including the hydrophobic effect and the entropy of folding. Herein, the contribution of these two effects and that of hydrophilic area burial is evaluated by analyzing Ala and Gly mutants implemented in three helices of apoflavodoxin. These data, combined with available data for similar mutations in other proteins (22 Ala/Gly mutations in α‐helices have been considered), allow estimation of the difference in backbone entropy between alanine and glycine and evaluation of its contribution and that of apolar and polar area burial to the helical stabilization typically associated to Gly→Ala substitutions. Alanine consistently stabilizes the helical conformation relative to glycine because it buries more apolar area upon folding and because its backbone entropy is lower. However, the relative contribution of polar area burial (which is shown to be destabilizing) and of backbone entropy critically depends on the approximation used to model the structure of the denatured state. In this respect, the excised‐peptide model of the unfolded state, proposed by Creamer and coworkers (1995), predicts a major contribution of polar area burial, which is in good agreement with recent quantitations of the relative enthalpic contribution of Ala and Gly residues to α‐helix formation. Proteins 2006. © 2006 Wiley‐Liss, Inc.
MKP1 mediates chemosensitizer effects of E1a in response to cisplatin in non-small cell lung carcinoma cells

The adenoviral gene E1a is known to enhance the antitumor effect of cisplatin, one of the cornerstones of the current cancer chemotherapy. Here we study the molecular basis of E1a mediated sensitivity to cisplatin in an experimental model of Non-small cell lung cancer. Our data show how E1a blocks the induction of autophagy triggered by cisplatin and promotes the apoptotic response in resistant cells. Interestingly, at the molecular level, we present evidences showing how the phosphatase MKP1 is a major determinant of cisplatin sensitivity and its upregulation is strictly required for the induction of chemosensitivity mediated by E1a. Indeed, E1a is almost unable to promote sensitivity in H460, in which the high expression of MKP1 remains unaffected by E1a. However, in resistant cell as H1299, H23 or H661, which display low levels of MKP1, E1a expression promotes a dramatic increase in the amount of MKP1 correlating with cisplatin sensitivity. Furthermore, effective knock down of MKP1 in H1299 E1a expressing cells restores resistance to a similar extent than parental cells. In summary, the present work reinforce the critical role of MKP1 in the cellular response to cisplatin highlighting the importance of this phosphatase in future gene therapy approach based on E1a gene.
Histological examinations of bone and cartilage in the axial skeleton of human triploidy fetuses

The aim of this study was to examine histologically bone and cartilage in vertebral corpora of axial skeletons of eight human triploid fetuses, gestational ages 14–25 weeks, CRL 100–200 mm. The results were compared to earlier studies on vertebral development in trisomies 21, 18, 13, and to normal corpora development. After radiography in frontal and lateral projections, the vertebral column was sectioned into cervical, thoracic and lumbar segments, decalcified, dehydrated, and embedded in paraffin. The blocks were serially sectioned in the vertical plane and stained with Toluidine blue and Alcian blue/van Gieson. The radiographic characteristics of the vertebral corpora observed in frontal and lateral projection varied from small cleft vertebral corpora to fusions between the individual corpora. Histological examination of the vertebral corpora confirmed the abnormal pattern of ossification seen radiographically. As a new finding abnormal metachromasia of the ground substance was observed in the cartilage. Marked borderlines were registered in the cartilage between regions with differences in metachromasia. These borderlines were similar but more extensive than borderlines observed previously in trisomies 21, 18 and 13.
Novel fully-depleted SiGe-on-insulator pMOSFETs with high-mobility SiGe surface channels

Novel strained SiGe-on-insulator (SGOI) pMOSFETs as well as a new fabrication technique of the SGOI substrates are demonstrated. The ultrathin strained SiGe as a channel layer is directly sandwiched by gate oxide and buried oxide layers. The mobility enhancement of 2.3 times higher than the universal mobility has been obtained for the p-MOSFET with a 19 nm-thick Si/sub 0.58/Ge/sub 042/ channel layer, which is formed by high-temperature oxidation of a Si/sub 0.9/Ge/sub 0.1/ layer grown on a Si-on-insulator (SOI) substrates. The concept of fully-depleted SGOI MOSFETs with the simple single-layer structure is promising for scaled SOI p-MOSFETs with high current drive.
The world of competitive Scrabble: Novice and expert differences in visuopatial and verbal abilities.

Competitive Scrabble players spend a mean of 4.5 hr a week memorizing words from the official Scrabble dictionary. When asked if they learn word meanings when studying word lists, only 6.4% replied "always," with the rest split between "sometimes" and "rarely or never. " Number of years of play correlated positively with expertise ratings, suggesting that expertise develops with practice. To determine the effect of hours of practice (M = 1,904), the authors compared experts with high-achieving college students on a battery of cognitive tests. Despite reporting that they usually memorize word lists without learning meanings, experts defined more words correctly. Reaction times on a lexical decision task (controlling for age) correlated with expertise ratings, suggesting that experts develop faster access to word identification. Experts' superiority on visuospatial processing was found for reaction time on 1 of 3 visuospatial tests. In a study of memory for altered Scrabble boards, experts outperformed novices, with differences between high and low expertise on memory for boards with structure-deforming transformations. Expert Scrabble players showed superior performance on selected verbal and visuospatial tasks that correspond to abilities that are implicated in competitive play.
A kinetic study of the crystallization process of noncrystalline indomethacin under isothermal conditions.

The crystallization process of noncrystalline indomethacin (IMC) obtained by the grinding and by the fusion method was analyzed by a kinetic method. The noncrystalline samples of IMC were the α form ground for 10 h at 4°C (GNCγ), the γ form ground for 10h at 4°C (GNCγ) and the fused solid (NC). Ten kinetic models were employed, and crystallinity was determined by X-ray diffractometry. Data obtained were used to determine the thermodynamic parameters and crystallization mechanism.Under isothermal conditions GNCγ crystallized in both the α and γ forms simultaneously. The GNCγ and NC crystallized in the γ form, and the results of the Hancock-Sharp method suggested that both crystallizations occurred by a two-dimensional phase boundary reaction; the activation energies (E) were estimated to be 24.1 and 27.2 kcal/mol. The crystallization rate of GNCγ was about 60 times faster than that of NC, and therefore NC was a very stable noncrystalline solid. These results suggest that there are several kinds of noncrystalline solids.
Short duration neoadjuvant chemotherapy followed by radiotherapy for advanced carcinoma of the cervix: results and prognostic variables.

PURPOSE The value of neoadjuvant chemotherapy in squamous cell carcinomas of the cervix has not been proven. It has been suggested that the potential benefit of this therapy on local and occult metastatic disease could be offset by delaying effective radiation therapy and selection of more aggressive tumor clones. This report examines the potential impact of short duration neoadjuvant chemotherapy on the response and outcome of advanced carcinoma of the cervix. MATERIALS AND METHODS Between 1993 and 1997, 37 patients with advanced squamous cell carcinoma of the cervix (FIGO Stages IIB to IV) were enrolled in a prospective nonrandomized study using short duration neoadjuvant chemotherapy. Median age was 57 years (range: 34-70). Twenty-one patients (57%) had Stage IIB disease, one (3%) had Stage IIIA, 11 (30%) Stage IIIB, and four (11%) had Stage IV disease. The average tumor diameter at presentation assessed by physical examination and by CT scan measurements was 5.3 + 1.9 cm and 5.3 + 1.4 cm, respectively. Patients received three cycles of chemotherapy consisting of cisplatin 50 mg/m2 and vincristine 1 mg/m2 for 1 dose and bleomycin 25 mg/m2 daily for three days. Cycles were repeated every ten days. All patients started definitive radiotherapy within a week from the end of chemotherapy. Radiation therapy consisted of whole pelvis radiotherapy followed by 1-3 sessions of low dose rate brachytherapy. RESULTS Response to neoadjuvant chemotherapy was as follows: seven patients (19%) had minor or no response, one patient had progressive disease, and 28 (76%) had more than 50% tumor reduction; 14 of them (38%) had no clinical evidence of residual tumor. Chemotherapy was discontinued in one patient after the second cycle because of significant changes in pulmonary function tests (PFT), and one patient developed a grade 4 urinary complication after radiotherapy. Median follow-up time for the whole group was 24 months (range: 1-67). Five-year actuarial rates of local control and disease-free survival were 47 and 42%, respectively. At three years, 20 patients (54%) were alive or had died without evidence of disease, and 17 (46%) had succumbed to their disease, with a median time to recurrence of 25 months. Stage and response to neoadjuvant chemotherapy had significant impact on survival, while age. tumor size, and menopausal status did not influence survival. CONCLUSIONS Our data indicate that short duration chemotherapy followed by definitive radiotherapy is well tolerated and feasible. However, despite a high rate of objective response (76%), and improved survival for responders, there was no obvious long-term survival benefit for the entire group.
Does the Early Bird Catch the Worm ? Firstborns and Their Financial Decisions

This paper examines whether birth order can explain variation in financial household decisions. I document that firstborns are more likely to save, to participate in the stock market, and to hold higher conditional equity shares. Consistent with higher financial sophistication, firstborns gather more information when making financial decisions. But when they are optimistic, firstborns seem to act more on their bias in their portfolio choices. Firstborns also tend to engage more in stock picking. Only part of the firstborn effect is captured by standard variables in household finance that also depend on birth order, such as education and income. The results are robust to controlling for parents’ age at birth, family fixed effects, and are not found for only children or last borns.
Amacrine-to-amacrine cell inhibition: Spatiotemporal properties of GABA and glycine pathways

Abstract We measured the spatial and temporal properties of GABAergic and glycinergic inhibition to amacrine cells in the whole-mount rabbit retina. The amacrine cells were parsed into two morphological classes: narrow-field cells with processes spreading less than 200 μm and wide-field cells with processes extending more than 300 μm. The inhibition was also parsed into two types: sustained glycine and transient GABA. Narrow-field amacrine cells receive 1) very transient GABAergic inhibition with a fast onset latency of 140 ± 16 ms decaying to 30% of the peak level within 208 ± 27 ms elicited broadly over a lateral distance of up to 1500 μm and 2) sustained glycinergic inhibition with a medium onset latency of 286 ± 23 ms that was elicited over a spatial area often broader than the processes of the narrow-field amacrine cells. Wide-field amacrine cells received sustained glycinergic inhibition but no broad transient GABAergic inhibition. Surprisingly, neither of these amacrine cell classes received sustained local GABAergic inhibition, commonly found in an earlier study of ganglion cells.
The healthfulness and prominence of sugar in child-targeted breakfast cereals in Canada.

INTRODUCTION The objective of this study was to compare the nutritional content and healthfulness of child-targeted and "not child-targeted" breakfast cereals and to assess the predominance of added sugar in these products. METHODS We collected data on the nutritional content of 262 unique breakfast cereals found in the five largest grocery store chains in Ottawa (Ontario) and Gatineau (Quebec). We noted the first five ingredients and the number of added sugars present in each cereal from the ingredients list. The various cereal brands were then classified as either "healthier" or "less healthy" using the UK Nutrient Profile Model. We assessed each cereal to determine if it was child-targeted or not, based on set criteria. Statistical comparisons were made between child and not child-targeted cereals. RESULTS 19.8% of all breakfast cereals were child-targeted, and these were significantly lower in total and saturated fat. Child-targeted cereals were significantly higher in sodium and sugar and lower in fibre and protein, and were three times more likely to be classified as "less healthy" compared to not child-targeted cereals. No child-targeted cereals were sugar-free, and sugar was the second most common ingredient in 75% of cereals. Six breakfast cereal companies had child-targeted product lines that consisted entirely of "less healthy" cereals. CONCLUSION There is a need for regulations that restrict food marketing to children and youth under the age of 17 on packaging to reduce their appeal to this age group. Children's breakfast cereals also need to be reformulated through government-set targets, or through regulation should compliance be deemed unacceptable.
Expectation modulates the response to subthalamic nucleus stimulation in Parkinsonian patients

Expectations about future events are known to trigger neural mechanisms that affect both perception and action. Here we report that different and opposite expectations of bad and good motor performance modulate the therapeutic effects of subthalamic nucleus stimulation in Parkinsonian patients who had undergone chronic implantation of electrodes for deep brain stimulation. By analyzing the effects of subthalamic stimulation on the velocity of movement of the right hand, we found hand movement to be faster when the patients expected a good motor performance. The expectation of good performance was induced through a placebo-like procedure, thus indicating that placebo-induced expectations have influence on the treatment outcome. All these effects occurred within minutes, suggesting that expectations induce neural changes very quickly.
User Modeling Approach for Dyslexic Students in Virtual Learning Environments

Dyslexia or reading disability is one of the most common learning disabilities. It is defined as a disorder manifested by difficulty in learning to read despite conventional instruction, adequate intelligence, and sociocultural opportunity. In this paper the authors focus on the potential benefits of the use of Information and Communication Technology ICT for students with dyslexia to promote the learning process, by considering the relationship between their learning style preferences and their cognitive traits in virtual learning environments. At this propose the authors investigated the relationship between dyslexic's learning style and cognitive trait within the hypothesis that dyslexic learners may have possible preferences in virtual learning environment, which may be used to improve the dyslexic user modelling. The aim of this paper is to provide an adaptive learning environment for users with dyslexia based on their learning styles preferences and their cognitive traits.
Quantification and source apportionment of the methane emission flux from the city of Indianapolis

We report the CH4 emission flux from the city of Indianapolis, IN, the site of the Indianapolis Flux Experiment (INFLUX) project for developing, assessing, and improving top-down and bottom-up approaches for quantifying urban greenhouse gas emissions. Using an aircraft-based mass balance approach, we find that the average CH4 emission rate from five flight experiments in 2011 is 135 ± 58 (1σ) moles s–1 (7800 ± 3300 kg hr–1). The effective per capita CH4 emission rate for Indianapolis is 77 kg CH4 person–1 yr–1, a figure that is less than the national anthropogenic CH4 emission (∼91 kg CH4 person–1 yr–1) but considerably larger than the global figure (∼48 kg CH4 person–1 yr–1). We consistently observed elevated CH4 concentrations at specific coordinates along our flight transects downwind of the city. Inflight investigations as well as back trajectories using measured wind directions showed that the elevated concentrations originated from the southwest side of the city where a landfill and a natural gas transmission regulating station (TRS) are located. Street level mobile measurements downwind of the landfill and the TRS supported the results of aircraft-based data, and were used to quantify the relative contributions from the two sources. We find that the CH4 emission from the TRS was negligible relative to the landfill, which was responsible for 33 ± 10% of the citywide emission flux. A regression of propane versus methane from aircraft flask samples suggests that the remaining citywide CH4 emissions (∼67%) derive from the natural gas distribution system. We discuss the combination of surface mobile observations and aircraft city-wide flux measurements to determine the total flux and apportionment to important sources.
Review of Children’s Identity Construction via Narratives

Understanding oneself is a fundamental human concern that starts early and continues throughout life. Identity construction is also a life-long process, but early childhood is the critical period for laying the foundation. Children’s identity construction proceeds through diverse perspectives which do not necessarily follow developmental steps. These perspectives include how children view themselves in relation to others through narratives, and how they embody themselves in the peer interactions of peer group and school. Self-identity is changed and transformed through interactions with environment and diverse experiences. The various ways children construct their identities reveal their efforts to “become. ” Understanding who we are in early childhood opens the door to acknowledging ourselves as significant human beings.