Miracle-dz/UniFAR-FTUs huggingface dataset:
Depletion of Phosphatidylinositol 4,5-Bisphosphate by Activation of Phospholipase C-coupled Receptors Causes Slow Inhibition but Not Desensitization of G Protein-gated Inward Rectifier K+ Current in Atrial Myocytes*

G protein-gated inwardly rectifier K+ current in atrial myocytes (IK(ACh)) upon stimulation with acetylcholine (ACh) shows a fast desensitizing component (t 1/2 ∼ 5 s). After washout of ACh, IK(ACh) recovers from fast desensitization within < 30 s. A recent hypothesis suggests that fast desensitization is caused by depletion of phosphatidylinositol 4,5-bisphosphate (PtIns(4,5)P2), resulting from costimulation of phospholipase C (PLC)-coupled M3 receptors (M3AChR). The effects of stimulating two established PLC-coupled receptors, α-adrenergic and endothelin (ETA), on IK(ACh) were studied in rat atrial myocytes. Stimulation of these receptors caused activation of IK(ACh) and inhibition of the M2AChR-activated current. In myocytes loaded with GTPγS (guanosine 5′-3-O-(thio)triphosphate), causing stable activation of IK(ACh), inhibition via α-agonists and ET-1 was studied in isolation. Stimulation of either type of receptor under this condition, via Gq/11, caused a slow inhibition (t 1/2∼50 s) by about 70%. No comparable effect on GTPγS-activated IK(ACh) was induced by ACh, suggesting that PLC-coupled M3AChRs are not functionally expressed in rat myocytes, which was supported by the finding that M3AChR transcripts were not detected by reverse transcriptase-polymerase chain reaction in identified atrial myocytes. Supplementing the pipette solution with PtIns(4,5)P2 significantly reduced inhibition of IK(ACh) but had no effect on fast desensitization. From these data it is concluded that stimulation of PLC-coupled receptors causes slow inhibition of IK(ACh) by depletion of PtIns(4,5)P2, whereas fast desensitization of IK(ACh) is not related to PtIns(4,5)P2depletion. As muscarinic stimulation by ACh does not exert inhibition of IK(ACh) comparable to stimulation of α1- and ETA receptors, expression of functional PLC-coupled muscarinic receptors in rat atrial myocytes is unlikely.
Numerical micromechanical investigation of interfacial strength parameters in a carbon fibre composite material

A finite element micromechanical model of a high strength composite material is subjected to a range of loading conditions to demonstrate its ability to predict failure. An investigation into the relative magnitude and distribution of the normal and shear stresses within the interface region of a single fibre embedded in a matrix region is compared to that of a multi-fibre representative volume element, where the fibre placement is statistically equivalent to that of a real material. A study is subsequently undertaken in which the relative magnitudes of the shear and normal strengths of the fibre–matrix interface are varied under transverse tension and shear. The results are interpreted with relation to the yield strength of the matrix. The predicted performance of the composite is shown to compare well with published experimental data, under transverse tension and in-plane shear. It is concluded that a single set of interface strength parameters can be used to represent the behaviour of the composite material. The results also show that interfacial shear strengths are expected to be equal, and higher than the interfacial normal strength.
Dual topology of the large envelope protein of duck hepatitis B virus: determinants preventing pre-S translocation and glycosylation

The biosynthesis and topology of the large envelope protein (L protein) of hepadnaviruses was investigated using the duck hepatitis B virus (DHBV) model, which also allows the study of hepadnavirus morphogenesis in experimentally infected hepatocytes. Results from proteolysis of virus particles and from the analysis of topology and posttranslational modification of L chains synthesized in vivo or in a cell-free system both support the presence of a mixed population of L-protein molecules with their N-terminal pre-S domain located either inside or outside the virus particle. During L biosynthesis and DHBV morphogenesis, pre-S, together with the neighboring transmembrane domain (TM-I), initially remained cytoplasmically disposed and was translocated only posttranslationally. Delayed pre-S translocation into a post-endoplasmic reticulum compartment is also indicated by the absence of glycosylation at a modification-competent pre-S glycosylation site. Major features of L-protein biosynthesis and of the resulting dual topology appear to be conserved between avian and mammalian hepadnaviruses, supporting the model that pre-S domains function in part either as an internal matrix for capsid envelopment or externally as a ligand for cellular receptor binding. However, differences in the mechanisms controlling pre-S translocation were revealed by the results of mutational analyses identifying and characterizing cis-acting determinants in pre-S that delay its cotranslational translocation. Our data from DHBV demonstrate the negative influence of a cluster of positively charged amino acid residues next to TM-I, a motif that is conserved among the avian but absent from mammalian hepadnaviruses. Additional control elements, which are apparently shared between both virus groups and which may serve in chaperone binding, were mapped by deletion analysis in the central part of pre-S.
Spatio-Temporal Correlations of Natural Images during Fixational Eye Movements

The spatio-temporal correlation of natural images during fixational eye instability is studied. The statistics of eye movements and static natural images are first analyzed separately and then combined to obtain an analytical formula for the correlation function. Previous work on this subject is presented and important shortcomings are pointed out. A more rigorous and general formula is derived and tested numerically.
Short intronic repeat sequences facilitate circular RNA production

Recent deep sequencing studies have revealed thousands of circular noncoding RNAs generated from protein-coding genes. The mechanism by which the spliceosome selects only certain exons to circularize is largely unknown. Liang and Wilusz used extensive mutagenesis of expression plasmids to show that miniature introns containing the splice sites along with short (∼30- to 40-nt) inverted repeats are sufficient to allow the intervening exons to circularize in cells. The intronic repeats and exonic sequences must collaborate with one another, and a functional 3′ end processing signal is required, suggesting that circularization may occur post-transcriptionally.
Intravitreal Triamcinolone Acetonide as Treatment of Ischemic Ophthalmopathy

Purpose To describe the clinical course of a patient receiving repeated intravitreal injections of triamcinolone acetonide (25 mg) as treatment of ischemic ophthalmopathy. Methods A 70-year-old patient with Waldenström disease presented with progressive iris neovascularization, vitreous hemorrhage, and ocular hypotony due to ischemic ophthalmopathy. Visual acuity was 0.05. Within 2.5 years, he received three intravitreal injections of 25 mg of triamcinolone acetonide. Additionally, penetrating keratoplasty and synechiolysis were performed during the follow-up. Results After each intravitreal injection, visual acuity and intraocular pressure increased, iris neovascularization regressed, and vitreous haze cleared up. Conclusions Intravitreal triamcinolone acetonide may induce regression of iris neovascularization, increase intraocular pressure, and improve visual acuity in eyes presenting with ocular hypotony, vitreous hemorrhage, and progressive intraocular neovascularization due to ischemic ophthalmopathy.
Allopolyploidy-Induced Rapid Genome Evolution in the Wheat (Aegilops–Triticum) Group

To better understand genetic events that accompany allopolyploid formation, we studied the rate and time of elimination of eight DNA sequences in F1 hybrids and newly formed allopolyploids of Aegilops and Triticum. In total, 35 interspecific and intergeneric F1 hybrids and 22 derived allopolyploids were analyzed and compared with their direct parental plants. The studied sequences exist in all the diploid species of the Triticeae but occur in only one genome, either in one homologous pair (chromosome-specific sequences [CSSs]) or in several pairs of the same genome (genome-specific sequences [GSSs]), in the polyploid wheats. It was found that rapid elimination of CSSs and GSSs is a general phenomenon in newly synthesized allopolyploids. Elimination of GSSs was already initiated in F1 plants and was completed in the second or third allopolyploid generation, whereas elimination of CSSs started in the first allopolyploid generation and was completed in the second or third generation. Sequence elimination started earlier in allopolyploids whose genome constitution was analogous to natural polyploids compared with allopolyploids that do not occur in nature. Elimination is a nonrandom and reproducible event whose direction was determined by the genomic combination of the hybrid or the allopolyploid. It was not affected by the genotype of the parental plants, by their cytoplasm, or by the ploidy level, and it did not result from intergenomic recombination. Allopolyploidy-induced sequence elimination occurred in a sizable fraction of the genome and in sequences that were apparently noncoding. This finding suggests a role in augmenting the differentiation of homoeologous chromosomes at the polyploid level, thereby providing the physical basis for the diploid-like meiotic behavior of newly formed allopolyploids. In our view, this rapid genome adjustment may have contributed to the successful establishment of newly formed allopolyploids as new species.
Ultrastructure of oval cells in children with chronic hepatitis B, with special emphasis on the stage of liver fibrosis: the first pediatric study.

AIM To investigate the ultrastructure of oval cells in children with chronic hepatitis B, with special emphasis on their location in areas of collagen fibroplasia. METHODS Morphological investigations were conducted on biopsy material obtained from 40 children, aged 3-16 years with chronic hepatitis B. The stage of fibrosis was assessed histologically using the arbitrary semiquantitative numerical scoring system proposed by Ishak et al. The material for ultrastructural investigation was fixed in glutaraldehyde and paraformaldehyde and processed for transmission-electron microscopic analysis. RESULTS Ultrastructural examination of biopsy specimens obtained from children with chronic hepatitis B showed the presence of two types of oval cells, the hepatic progenitor cells and intermediate hepatic-like cells. These cells were present in the parenchyma and were seen most commonly in areas of intense periportal fibrosis (at least stage 2 according to Ishak et al) and in the vicinity of the limiting plate of the lobule. The activated nonparenchymal hepatic cells, i.e. transformed hepatic stellate cells and Kupffer cells were seen in close proximity to the intermediate hepatic-like cells. CONCLUSION We found a distinct relationship between the prevalence of oval cells (hepatic progenitor cells and intermediate hepatocyte-like cells) and fibrosis stage in pediatric patients with chronic hepatitis B.
An Analysis of Annotation of Verb-Noun Idiomatic Combinations in a Parallel Dependency Corpus

While working on valency lexicons for Czech and English, it was necessary to define treatment of multiword entities (MWEs) with the verb as the central lexical unit. Morphological, syntactic and semantic properties of such MWEs had to be formally specified in order to create lexicon entries and use them in treebank annotation. Such a formal specification has also been used for automated quality control of the annotation vs. the lexicon entries. We present a corpus-based study, concentrating on multilayer specification of verbal MWEs, their properties in Czech and English, and a comparison between the two languages using the parallel Czech-English Dependency Treebank (PCEDT). This comparison revealed interesting differences in the use of verbal MWEs in translation (discovering that such MWEs are actually rarely translated as MWEs, at least between Czech and English) as well as some inconsistencies in their annotation. Adding MWE-based checks should thus result in better quality control of future treebank/lexicon
Ipsilateral Versus Contralateral Ovary Selection of Dominant Follicle in Succeeding Cycle

There is still confusion as to whether ovulation in a succeeding cycle is a random event or is more likely to occur at the ipsilateral or contralateral ovary. Both histologic and sonographic data support alternating ovulation. Some ultrasound studies have suggested that ipsilateral ovulation is more likely in succeeding cycles, and another found rightsided ovulation to be more common. Because many of the studies are based upon small numbers, we initiated a large study to determine the more likely side of ovulation. Furthermore, the present investigation attempted to confirm biochemically the true existence of the dominant follicle by demonstrating appropriate serum estradiol levels. Evaluation of natural cycles (286 pairs) demonstrated 52.4% ipsilateral ovulation and 47.6% contralateral ovulation. Rightsided ovulation occurred in 54.5% of cycles. Our data suggest that the side of ovulation in successive cycles is not influenced by the side of ovulation in the preceding cycle.
Clarification requests in everyday interaction involving children with cochlear implants

Abstract The aim of the present study is to explore the form and function of clarification request sequences in interaction involving children with cochlear implants. Clarification request sequences are investigated in everyday interaction, and it is demonstrated that children with CI use both general/open and specific requests for clarification. It is also shown that there is relatively lower frequency of requests for clarification in interactions involving children with CI with high intelligibility scores. The results may be useful in clinical assessment and intervention demonstrating the importance of assessing interactional ability in everyday interaction.
What new information pediatric autopsies can provide: a retrospective evaluation of 100 consecutive autopsies using family-centered criteria.

OBJECTIVE To determine the proportions of pediatric autopsies yielding various types of new information (eg, genetic diagnosis, additional explanation) that might be valued by families. DESIGN Retrospective case series analysis. SETTING Large urban children's hospital. PARTICIPANTS One hundred consecutive autopsies, 2003-2004. INTERVENTION Using both traditional criteria and a novel classification scheme developed with expert clinicians and nonmedical parent faculty, 3 reviewers independently assessed each case for new information found at autopsy. Classifications were based on unanimous consensus. MAIN OUTCOME MEASURE Proportions of autopsies yielding new information. RESULTS Decedents' ages ranged from 1 to 24 years. Using traditional criteria, major unexpected findings related to death occurred in 28% of the autopsies. Applying our novel criteria to the same 100 autopsies, we found new information that had the potential to further clarify the cause(s) of a child's death (53% of cases); inform the future reproductive choices of either the parents (10%) or siblings (8%); affect siblings' future health care (6%); or contribute to patient care quality control (36%) or publishable knowledge (7%). CONCLUSIONS Pediatric autopsies can yield different types of information that may be important to families. While the proportion of autopsies providing specific types of new information will vary between hospitals (depending on case mix, autopsy policies, and clinician/pathologist expertise) and across time (depending on available diagnostic modalities), hospital-specific data classified in this manner may be useful to physicians counseling families about autopsy.
Insomnia and risk of cardiovascular disease: a meta-analysis

Objective: Increasing evidence suggests an association between insomnia and cardiovascular disease. We performed a systematic review with meta-analysis of all the available prospective studies that investigated the association between insomnia and risk of developing and/or dying from cardiovascular disease. Design: Systematic review and meta-analysis of prospective cohort studies. Methods: We conducted an electronic literature search through MedLine, Embase, Google Scholar, Web of Science, The Cochrane Library and bibliographies of retrieved articles up to December 2011. Studies were included if they were prospective, had assessment of insomnia or sleep complaints at baseline, evaluated subjects free of cardiovascular disease at baseline and measured the association between insomnia and risk of developing and/or dying from cardiovascular disease. Results: After the review process 13 prospective studies were included in the final analysis. These studies included 122,501 subjects followed for a time ranging from three to 20 years. A total of 6332 cardiovascular events occurred during the follow-up. Insomnia was assessed through questionnaire and defined as either difficulty of initiating or maintaining sleep or presence of restless, disturbed nights. The cumulative analysis for all the studies under a random-effects model showed that insomnia determined an increased risk (+45%) of developing or dying from cardiovascular disease during the follow-up (relative risk 1.45, 95% confidence interval 1.29–1.62; p < 0.00001), with no evidence of heterogeneity across the studies (I2: 19%; p = 0.14). Conclusion: Insomnia is associated with an increased risk of developing and/or dying from cardiovascular disease.
Benefit and projected cost‐effectiveness of anastrozole versus tamoxifen as initial adjuvant therapy for patients with early‐stage estrogen receptor–positive breast cancer

Women who have estrogen receptor (ER)‐positive disease with postmenopausal onset and who receive tamoxifen as standard adjuvant treatment constitute the largest subgroup of patients with breast cancer. Recent data from the ATAC (‘Arimidex, Tamoxifen Alone or in Combination’) randomized trial indicate that anastrozole significantly reduces breast cancer recurrence rates but does not provide any advantage in terms of survival at 4 years posttreatment. Furthermore, anastrozole and tamoxifen were found to have different toxicity profiles. The goals of the current study were to estimate the disease‐free survival (DFS) rates and potential survival benefits associated with anastrozole use and to determine whether the incremental cost‐effectiveness (ICE) was low enough to warrant an immediate switch to the use of this agent, as the long‐term conclusions of the ATAC trial will not be available for several years.
Lack of effects of dietary folate intake on risk of breast cancer: an updated meta-analysis of prospective studies.

BACKGROUND Epidemiological findings are controversial relating to the relationship between dietary folate intake and the risk of breast cancer. We therefore conducted a meta-analysis of prospective cohort studies to clarify this association. MATERIALS AND METHODS PUPMED, EMBASE, and MEDLINE databases were searched for all relevant literature published in English from January 1, 1966 to August 2013. Summary relative risk (RR) and 95% confidence intervals (CIs) were calculated using a fixed or random effects model. RESULTS Dietary folate intake was not significantly associated with the risk of breast cancer. The combined PR with 95% CI for the highest vs. lowest category dietary intake of folate [fifteen studies; 1,836,566 participants and 24,083 patients with breast cancer] was 0.98 (0.90-1.05). Among subgroup analysis by menstrual status, hormonal status and the consumption of alcohol, methionine and vitamin B12, no significant association was observed for the dietary intake of folate and the risk of breast cancer. Dose-response analysis showed that a 220 μg/day increment in dietary folate intake was not associated with the risk of breast cancer. CONCLUSIONS Our findings indicate that dietary folate intake has no significant effect on the risk of breast cancer.
Restricted completion of sparse partial Latin squares

Abstract An n × n partial Latin square P is called α-dense if each row and column has at most αn non-empty cells and each symbol occurs at most αn times in P. An n × n array A where each cell contains a subset of {1,…, n} is a (βn, βn, βn)-array if each symbol occurs at most βn times in each row and column and each cell contains a set of size at most βn. Combining the notions of completing partial Latin squares and avoiding arrays, we prove that there are constants α, β > 0 such that, for every positive integer n, if P is an α-dense n × n partial Latin square, A is an n × n (βn, βn, βn)-array, and no cell of P contains a symbol that appears in the corresponding cell of A, then there is a completion of P that avoids A; that is, there is a Latin square L that agrees with P on every non-empty cell of P, and, for each i, j satisfying 1 ≤ i, j ≤ n, the symbol in position (i, j) in L does not appear in the corresponding cell of A.
Ambient Air Pollution and Cardiovascular Emergency Department Visits

Background: Despite evidence supporting an association between ambient air pollutants and cardiovascular disease (CVD), the roles of the physicochemical components of particulate matter (PM) and copollutants are not fully understood. This time-series study examined the relation between ambient air pollution and cardiovascular conditions using ambient air quality data and emergency department visit data in Atlanta, Georgia, from January 1, 1993, to August 31, 2000. Methods: Outcome data on 4,407,535 emergency department visits were compiled from 31 hospitals in Atlanta. The air quality data included measurements of criteria pollutants for the entire study period, as well as detailed measurements of mass concentrations for the fine and coarse fractions of PM and several physical and chemical characteristics of PM for the final 25 months of the study. Emergency department visits for CVD and for cardiovascular subgroups were assessed in relation to daily measures of air pollutants using Poisson generalized linear models controlling for long-term temporal trends and meteorologic conditions with cubic splines. Results: Using an a priori 3-day moving average in single-pollutant models, CVD visits were associated with NO2, CO, PM2.5, organic carbon, elemental carbon, and oxygenated hydrocarbons. Secondary analyses suggested that these associations tended to be strongest with same-day pollution levels. Conclusions: These findings provide evidence for an association between CVD visits and several correlated pollutants, including gases, PM2.5, and PM2.5 components.
Functional Overlap between eIF4G Isoforms in Saccharomyces cerevisiae

Initiation factor eIF4G is a key regulator of eukaryotic protein synthesis, recognizing proteins bound at both ends of an mRNA to help recruit messages to the small (40S) ribosomal subunit. Notably, the genomes of a wide variety of eukaryotes encode multiple distinct variants of eIF4G. We found that deletion of eIF4G1, but not eIF4G2, impairs growth and global translation initiation rates in budding yeast under standard laboratory conditions. Not all mRNAs are equally sensitive to loss of eIF4G1; genes that encode messages with longer poly(A) tails are preferentially affected. However, eIF4G1-deletion strains contain significantly lower levels of total eIF4G, relative to eIF4G2-delete or wild type strains. Homogenic strains, which encode two copies of either eIF4G1 or eIF4G2 under native promoter control, express a single isoform at levels similar to the total amount of eIF4G in a wild type cell and have a similar capacity to support normal translation initiation rates. Polysome microarray analysis of these strains and the wild type parent showed that translationally active mRNAs are similar. These results suggest that total eIF4G levels, but not isoform-specific functions, determine mRNA-specific translational efficiency.