Miracle-dz/UniFAR-FTUs huggingface dataset:
The anchor site of telomerase from Euplotes aediculatus revealed by photo-cross-linking to single- and double-stranded DNA primers

Telomerase is a ribonucleoprotein enzyme that adds telomeric sequence repeats to the ends of linear chromosomes. In vitro, telomerase has been observed to add repeats to a DNA oligonucleotide primer in a processive manner, leading to the postulation of a DNA anchor site separate from the catalytic site of the enzyme. We have substituted photoreactive 5-iododeoxypyrimidines into the DNA oligonucleotide primer d(T4G4T4G4T4G2) and, upon irradiation, obtained cross-links with the anchor site of telomerase from Euplotes aediculatus nuclear extract. No cross-linking occurred with a primer having the same 5' end and a nontelomeric 3' end. These cross-links were shown to be between the DNA primer and (i) a protein moiety of approximately 130 kDa and (ii) U51-U52 of the telomerase RNA. The cross-linked primer could be extended by telomerase in the presence of [alpha-32P]dGTP, thus indicating that the 3' end was bound in the enzyme active site. The locations of the cross-links within the single-stranded primers were 20 to 22 nucleotides upstream of the 3' end, providing a measure of the length of DNA required to span the telomerase active and anchor sites. When the single-stranded primers are aligned with the G-rich strand of a Euplotes telomere, the cross-linked nucleotides correspond to the duplex region. Consistent with this finding, a cross-link to telomerase was obtained by substitution of 5-iododeoxycytidine into the CA strand of the duplex region of telomere analogs. We conclude that the anchor site in the approximately 130-kDa protein can bind duplex as well as single-stranded DNA, which may be critical for its function at chromosome ends. Quantitation of the processivity with single-stranded DNA primers and double-stranded primers with 3' tails showed that only 60% of the primer remains bound after each repeat addition.
Frailty and Social Vulnerability in Mexican Deprived and Rural Settings

Objective: To estimate the prevalence of frailty in a sample of rural elderly living in socially vulnerable circumstances as well as to determine its correlates. Method: Cross-sectional study of 558 rural elderly participating in a prospective study conducted in Mexico. Frailty was defined using the Fried criteria. Ordinal logistic regression model was used to identify the correlates of frailty levels. Results: Prevalence of frailty was 8.6%. Disability in basic activities of daily living and illiteracy increase the probability of being pre-frail and/or frail (odds ratio [OR] = 2.72, p < .01; OR = 1.45, p = .05, respectively), while living in households with higher socioeconomic status reduces this probability (OR = 0.85, p < .01). Discussion: A high prevalence of frailty was found among these young elderly, who did not yet fully show adverse health events. Also the social vulnerability of rural elderly is associated with frailty status. These findings highlight the health needs of socially and economically vulnerable elderly population.
Protective Effect of Brazilian Propolis Against Hepatic Oxidative Damage in Rats with Water‐immersion Restraint Stress

In the present study we examined the protective effect of Brazilian propolis against hepatic oxidative damage in rats with water‐immersion restraint stress (WIRS) in comparison with that of vitamin E (VE). Fasted rats orally received Brazilian green propolis ethanol extract (BPEE; 10, 50 or 100 mg/kg), VE (250 mg/kg) or vehicle at 30 min before the onset of WIRS. Exposure of vehicle‐treated rats to 6 h of WIRS caused liver cell damage, judging from the levels of serum alanine aminotransferase and aspartate aminotransferease, increased hepatic lipid peroxide, NOx contents and myeloperoxidase activity, and decreased hepatic non‐protein SH, ascorbic acid contents and superoxide dismutase activity. Preadministration of BPEE (50 or 100 mg/kg) or VE to the stressed rats protected against the hepatic damage and attenuated the increased hepatic lipid peroxide and NOx contents and myeloperoxidase activity and the decreased hepatic non‐protein SH and ascorbic acid contents and superoxide dismutase activity. These protective effects of BPEE (50 mg/kg) were greater than those of BPEE (100 mg/kg) and were almost equal to those of VE. These results indicate that BPEE protects against hepatic oxidative damage in rats exposed to WIRS possibly through its antioxidant and antiinflammatory properties such as VE. Copyright © 2012 John Wiley & Sons, Ltd.
A Deep Choice Model

Human choice is complex in two ways. First, human choice often shows complex dependency on available alternatives. Second, human choice is often made after examining complex items such as images. The recently proposed choice model based on the restricted Boltzmann machine (RBM choice model) has been proved to represent three typical phenomena of human choice, which addresses the first complexity. We extend the RBM choice model to a deep choice model (DCM) to deal with the features of items, which are ignored in the RBM choice model. We then use deep learning to extract latent features from images and plug those latent features as input to the DCM. Our experiments show that the DCM adequately learns the choice that involves both of the two complexities in human choice.
Transcranial color-coded duplex sonography in the evaluation of collateral flow through the circle of Willis.

PURPOSE To determine the sensitivity, specificity, and positive and negative predictive values of transcranial color-coded duplex sonographic (TCCD) evaluation of cross flow through the anterior (ACoA) and posterior (PCoA) communicating arteries in patients with occlusive cerebrovascular disease. METHODS We studied prospectively 132 patients (37 women, 95 men; mean age, 60 years) with stenoses of more than 69% reduction in vessel diameter (n = 93) and occlusions (n = 52) of the internal carotid artery, and three occlusions of the basilar artery. The sonographer was aware of extracranial sonographic findings but was blinded to the results of cerebral angiography. RESULTS Nine patients (7%) with thick bones preventing transtemporal insonation and three patients (3%) with occlusions of the middle (n = 3) and anterior (n = 1) cerebral arteries were excluded. Sensitivity of TCCD for detection of collateral flow through the ACoA in patients with occlusive carotid artery disease was 98%, specificity was 100%, positive predictive value was 100%, and negative predictive value was 98%. The corresponding values for the PCoA were 84%, 94%, 94%, and 84%, respectively. All three functional PCoAs were identified in patients with occluded basilar arteries. CONCLUSION TCCD is a valuable method for noninvasive evaluation of cross flow through the ACoA in patients with adequate sonographic windows. However, TCCD evaluation of cross flow through the PCoA is less reliable, because hemodynamic criteria may cause falsely positive and falsely negative results.
smARTbox A Portable Setup for Intelligent Interactive Applications

This paper presents a semi-immersive, multimodal fish tank simulation realized using the smARTbox, an out-of-the-box platform for intelligent interactive applications. The smARTbox provides portability, stereoscopic visualization, marker-less user tracking and direct interscopic touch input. Off-the-shelf hardware is combined with a state-of-the-art simulation platform to assemble a powerful system environment, which facilitates direct (touch) and indirect (movement) interaction
High-b-value diffusion-weighted MR imaging for pretreatment prediction and early monitoring of tumor response to therapy in mice.

PURPOSE To evaluate the use of diffusion-weighted magnetic resonance (MR) imaging with standard and high b values for pretreatment prediction and early detection of tumor response to various antineoplastic therapies in an animal model. MATERIALS AND METHODS Mice bearing C26 colon carcinoma tumors were treated with doxorubicin (n = 25) and with aminolevulinic acid-based photodynamic therapy (n = 23). Fourteen mice served as controls. Conventional T2-weighted fast spin-echo and diffusion-weighted MR images were acquired once before therapy and at 6, 24, and 48 hours after treatment. Pretreatment and early (1-2 days) posttreatment water diffusion parameters were calculated and compared with later changes in tumor volumes measured on conventional MR images by using the Pearson correlation test. RESULTS In chemotherapy-treated tumors, a significant correlation (P <.002, r = 0.6) was observed between diffusion parameters that reflected tumor viability, measured prior to treatment, and changes in tumor volumes after therapy. This correlation implies that tumors with high pretreatment viability will respond better to chemotherapy than more necrotic tumors. In tumors treated with photodynamic therapy, no such correlation was found. Changes observed in water diffusion 1-2 days after treatment significantly correlated with later tumor growth rate for both therapies (P <.002, r = 0.54 for photodynamic therapy; P <.0003, r = 0.61 for chemotherapy). CONCLUSION High-b-value diffusion-weighted MR imaging has potential use for the early detection of response to therapy and for predicting treatment outcome prior to initiation of chemotherapy.
Firm Growth and Technical Efficiency in Ethiopia: The Role of Firm Size and Finance

The performance of manufacturing firms can play a crucial rule in spurring economic growth and international competency. However, it has received little attention in developing countries particularly in Sub-Saharan Africa (SSA). Using firm level data from 2000 to 2008 survey, this paper empirically investigates the key determinants of growth and technical efficiency of Ethiopian manufacturing establishments focusing on the impact of size and finance. The empirical result using dynamic panel data estimation suggest that small and young firms grow more rapidly. Leverage ratio and cash flow are also main determinants of firm growth. However, they have heterogeneous effect. While, the availability of internal finance significantly affect the growth of smaller firms, leverage (borrowing) represent a binding constraint for growth of large firms. Firmi¯s asset, labour quality, ownership and legal status are also binding constraints for growth of firm in Ethiopia. Moreover, a stochastic frontier analysis of the production function shows that there is significant difference in efficiency scores across firms. The result shows that efficiency score increases with firm size and cash flow but decrease with borrowing.
Measuring Fair Value When Markets Malfunction: Evidence from the Financial Crisis

In this paper we focus on fair value measurements in the Financial Crisis and its (continuing) aftermath. We consider different ways of measuring fair value; and we use the experience of economies under stress, and where markets deviate significantly from textbook models of symmetric information and perfect competition, to trace some perverse economic consequences of fair value measurement choices prescribed by accounting standard setters. We draw on anecdotal and case evidence from the banking crisis and its aftermath for the wider economy. The discussion focuses particularly on banks’ balance sheets and then on pension liabilities across all sectors.
Low Level of Optimism Predicts Initiation of Psychotherapy for Depression: Results from the Finnish Public Sector Study

Background: The patient’s personality may be one of the many factors that contribute to the decision to initiate a certain treatment for depression. The aim of this study was to examine whether dispositional optimism and pessimism play a role in the initiation of psychotherapy as the treatment for new-onset depression in previously nondepressed public sector employees. Methods: This prospective observational cohort study included 38,717 (mean age: 45 years; 76% female) public sector employees who responded to a survey in 1997, 2000–2001 and/or 2004 and had no history of depression at cohort entry. Dispositional optimism and pessimism were assessed via the revised Life Orientation Test and linked to individual records of indicators of depression onset in comprehensive national health registers, and of long-term psychotherapy for depression in particular. Results: During a mean follow-up of 4.0 years, 1,616 (4%) incident cases of depression were observed. Of them, 79 started long-term, state-subsidized psychotherapy for depression. A 1-unit increase in mean optimism score was associated with a 38% lower likelihood of initiating psychotherapy as a treatment for depression and a 32% lower likelihood of depressive disorder in general during follow-up. Pessimism score was not associated with initiation of psychotherapy for depression, but a 1-unit increase in pessimism score was associated with a 28% increase in the likelihood of depressive disorder. These findings were robust to adjustments for demographics, health risk behaviors and somatic diseases at baseline. Conclusion: This study suggests that although both low optimism and high pessimism increase the risk for depression, only low optimism influences the initiation of psychotherapy as a treatment modality for depression. This could imply that depressed patients with low optimism should receive more attention in the beginning of the depressive episode than patients with high optimism.
Lack of Evidence for Association between Endothelial Nitric Oxide Synthase Gene Polymorphisms and Coronary Artery Disease in the Australian Caucasian Population

Background Genetic polymorphism in the gene for endothelial nitric oxide synthase (eNOS) has been identified as a potential risk factor for the development of premature coronary artery disease (CAD). We determined whether the eNOS 4ab, G894T, and T-786C polymorphisms are associated with premature coronary artery disease. Design A case-control study. Methods PCR-based assays were used to compare the frequency of eNOS gene polymorphisms in 573 Caucasian subjects aged under 50 years presenting with symptomatic CAD and documented by coronary angiography, with or without myocardial infarction, to that of 624 similarly aged community controls without a history of symptomatic CAD. Results We found no difference in the frequency of 4ab genotypes between cases and controls: In the CAD subjects, the 4aa, 4ab, and 4bb genotype frequencies were 1.9%, 24.3% and 73.8% respectively, compared to 2.2%, 25.5% and 72.3% respectively for the controls. There was also no significant difference between cases and controls in the frequency of any allele (4a/4b, 894G/894T, −786C/-786T), or genotype for any of the polymorphisms. Similarly, logistic regression analysis showed no evidence for an association of the polymorphisms with premature CAD or myocardial infarction or any indication of an interaction between the polymorphisms and other CAD risk factors, including smoking. Conclusions In a large case-control study, and in contrast to some earlier positive findings by others, we have found no evidence for an association between several eNOS gene polymorphisms and premature CAD in an Australian Caucasian population.
Epidemiology of psychotropic medication use: Comparison of sales, prescriptions and survey data in Iceland

Public health issues, medical and socio-demographics, related to use of psychotropic medications and to increasing sale of antidepressants and hypnotics need to be explored. The aim of this study was to investigate the use of antidepressants, tranquillizers and sedatives nationally and its connection with health and demographic factors, by comparing: 1) sales data and 2) prescription data for outpatients with 3) self-reported use of a random sample of the population aged 18–75 years. In 2001, the sales of psychopharmaca was 168.8 daily defined doses (DDD)/1000/day, thereof 46.6% were antidepressants mainly for outpatients; one-third of hypnotics and tranquillizers were used for inpatients; 134.2 DDD/1000/day were filled by outpatients. Almost 20% of the respondents in the survey had used one or more of these drugs for some time during the preceding 12 months. Treatment adherence for antidepressants was 56%, lower for women than men. The probability of psychotropic drug use for mental complaints is 52% when controlled for other covariates. Any observed gender difference in the community survey is related to differences in the covariates, e.g. women are more likely to seek a doctor than men. The age effect on self-reported use in the community survey is related to hypnotics. The use of psychotropic medicaments is primarily driven by mental health complaints, but not by gender or age, except the use of hypnotics, which increases with age. The difference between self-reported use and prescriptions filled may reflect compliance problems in psychiatric treatment.
Clinical parameters in 74 consecutive patients shunt operated for normal pressure hydrocephalus

ABSTRACT Seventy four consecutive patients diagnosed as normal pressure hydrocephalus (NPH) and operated with a ventriculo‐peritoneal shunt were followed prospectively for an average of 2.1 years. The mean age was 64 years. The effect of the operation was estimated by calculating 6 indices expression social functioning, neurological signs, gait ability, continence, psychometric performance and psychiatric condition. Ninety‐six % had mental symptoms, 95% gait disturbances and 75% incontinence. Improvement was observed in 78% after shunt surgery, while 22% deteriorated. Psychiatric improvement was seen in 80% and 76% improved in gait ability. Improvement was highest in the group caused by subarachnoid hemorrhage (98%) while 73% with idiopathic NPH improved. Old age was not correlated to poorer response, while long‐standing pre‐operative symptoms yielded worse results. No single symptom or sign could predict a positive outcome of the operation. Eleven % of the patients could leave long‐term care institutions and there was a 36% reduction of aid in daily living. Complications to shunt surgery were observed in 50% of the patients and shunt related mortality was 1%. Shunt malfunction was the most frequent complication (31%) followed by infection (19%). Epilepsy developed in 9% after surgery. All shunt complication except one appeared within the first year after surgery.
The Role of Putative Phosphorylation Sites in the Targeting and Shuttling of the Aquaporin-2 Water Channel*

In renal collecting ducts, a vasopressin-induced cAMP increase results in the phosphorylation of aquaporin-2 (AQP2) water channels at Ser-256 and its redistribution from intracellular vesicles to the apical membrane. Hormones that activate protein kinase C (PKC) proteins counteract this process. To determine the role of the putative kinase sites in the trafficking and hormonal regulation of human AQP2, three putative casein kinase II (Ser-148, Ser-229, Thr-244), one PKC (Ser-231), and one protein kinase A (Ser-256) site were altered to mimic a constitutively non-phosphorylated/phosphorylated state and were expressed in Madin-Darby canine kidney cells. Except for Ser-256 mutants, seven correctly folded AQP2 kinase mutants trafficked as wild-type AQP2 to the apical membrane via forskolin-sensitive intracellular vesicles. With or without forskolin, AQP2-Ser-256A was localized in intracellular vesicles, whereas AQP2-S256D was localized in the apical membrane. Phorbol 12-myristate 13-acetate-induced PKC activation following forskolin treatment resulted in vesicular distribution of all AQP2 kinase mutants, while all were still phosphorylated at Ser-256. Our data indicate that in collecting duct cells, AQP2 trafficking to vasopressin-sensitive vesicles is phosphorylation-independent, that phosphorylation of Ser-256 is necessary and sufficient for expression of AQP2 in the apical membrane, and that PMA-induced PKC-mediated endocytosis of AQP2 is independent of the AQP2 phosphorylation state.
Structural characterization of two interchangeable conformations of a 2-aminofluorene-modified DNA oligomer by NMR and energy minimization.

One- and two-dimensional NMR spectroscopy and energy minimization calculations were used to investigate the conformation of a 2-aminofluorene- (AF-) modified model human c-H-ras1 protooncogene codon 61 deoxyoligonucleotide duplex, d(C1-A2-C3-C4-A5- [AF-G6]-G7-A8-A9-C10). -d(G11-T12-T13-C14-C15-T16 -G17-G18-T19-G20), in which the AF adduct is located at the third base of codon 61 with cytosine as the complementary nucleotide. Two interchangeable conformations of the AF-modified duplex, referred to as the external-AF conformation and the inserted-AF conformation, were determined from the NMR data. An analysis of the coalescence of resonances led to the estimation that the chemical exchange lifetime is greater than 3 ms but less than 20 ms at 30 degrees C, pH 7. In the external-AF conformation, Watson-Crick base-pair formation is observed for all 10 complementary nucleotides, including the AF-G6.C15 base pair. In the inserted-AF conformation, 9 of the 10 complementary bases form Watson-Crick base pairs; the AF-G6 imino proton exhibits no evidence of hydrogen bond formation with its complementary cytosine. Several NOEs between aminofluorene protons and DNA protons show that the AF moiety in the inserted-AF conformation stacks between the adjacent A5.T16 and G7.C14 base pairs. Solvated energy minimization calculations using distance restraints obtained from NOESY data at 2 degrees C with a 100-ms mixing time were performed to obtain representative structures of the external-AF and inserted-AF conformations. The external-AF conformer has the AF moiety protruding out of the major groove of a relatively unperturbed DNA duplex, leaving intact Watson-Crick base pairing for the AF-G6.C15 bases. Thus, the external-AF conformer may represent a visualization of a conformation that allows faithful replication. The inserted-AF conformer has the AF moiety stacked within the DNA helix, breaking the Watson-Crick base pairing of the modified guanine and its complementary cytosine and displacing the guanine and cytosine into the grooves. We label the inserted-AF conformer as a premutagenic conformation to reflect the displacement of the modified guanine. Interconversion between the structurally distinct external-AF and inserted-AF conformers takes place on a time scale of the same order as DNA replication. We have labeled this interconversion as a mutagenic switch to highlight a possible conformational equilibrium that may be important in replication.