Miracle-dz/UniFAR-FTUs huggingface dataset:
Catecholestrogens induce oxidative stress and malignant transformation in human endometrial glandular cells: Protective effect of catechol‐O‐methyltransferase

Prolonged exposure to unopposed estrogens is a major risk factor for the development of endometrial cancer. Oxidative metabolism of estradiol (E2) into the catecholestrogens (CEs), 4‐hydroxyestradiol (4‐OHE2) and 2‐hydroxyestradiol (2‐OHE2), may play an important role in estrogen carcinogenicity. CEs can be oxidized to the corresponding ortho‐quinone derivatives with concomitant formation of the reactive oxygen species (ROS). Catechol‐O‐methyltransferase (COMT) is the major enzyme involved in the detoxification of CEs in extrahepatic tissues. We investigated the potential of E2, 2‐OHE2 and 4‐OHE2 to induce microsatellite instability (MSI) and neoplastic transformation of immortalized human endometrial glandular (EM) cells. We also investigated the functional significance of COMT gene expression on modulating the effects of E2 and CEs in EM cells. Our data indicated that E2 and 4‐OHE2 induce MSI, ROS and neoplastic transformation in EM cells. The capacity of E2 and its catechol metabolites to induce MSI, ROS and neoplastic transformation in EM cells is ranked as follows: 4‐OHE2 > E2 > 2‐OHE2. Knockdown of COMT expression in EM cells resulted in increased estrogenic milieu and increased estrogen‐induced cell proliferation. More importantly, knockdown of COMT increased the propensity of E2 or CEs to induce ROS, MSI and neoplastic transformation of EM cells. In contrast, overexpression of COMT in EM cells significantly reduced the cellular estrogenic milieu and protected against E2‐ or CEs‐induced, ROS, MSI and neoplastic transformation. The capacity of E2 or CEs to induce neoplastic transformation of human endometrial glandular cells in vitro may suggest that E2‐induced endometrial cancer is mediated by its metabolism into CEs. Our study clearly indicates that COMT gene expression plays a critical role in modulating the hormonal and carcinogenic effects of E2 and CEs and, consequently, modifies the risk for E2‐induced endometrial cancer. To the best of our knowledge, this is the first study to (i) demonstrate the potential capacity of estrogen and its catechol metabolites to induce neoplastic transformation of immortalized human endometrial glandular cells; and (ii) illustrate the important role of COMT gene expression in protecting against E2‐induced endometrial cancer. © 2008 Wiley‐Liss, Inc.
Defining, Designing, and Evaluating Peripheral Displays: An Analysis Using Activity Theory

ABSTRACT Peripheral displays are an important class of applications that improve our ability to balance multiple activities. However, peripheral display innovation and development has suffered because much of the past work has been technology driven: There exists little theoretical understanding of how they operate in relation to people's everyday lives. In response to this, we present a framework for understanding, designing, and evaluating peripheral displays based on Activity Theory. We argue that peripheral displays are information displays that become unobtrusive to users. As this quality depends on the context of use, we present a framework for describing peripheral displays based on the number and types of activities they support. Furthermore, we argue that different types of displays require different approaches to evaluation. From our own work and a review of related literature we derive a set of general evaluation criteria for peripheral displays (appeal, learnability, awareness, effects of breakdowns, and distraction). We then describe approaches for evaluating these criteria for different types of peripheral displays and present a case study to illustrate the value of our Activity Theory evaluation framework in practice.
#mytweet via Instagram: Exploring user behaviour across multiple social networks

We study how users of multiple online social networks (OSNs) employ and share information by studying a common user pool that use six OSNs - Flickr, Google+, Instagram, Tumblr, TWitter, and YouTube. We analyze the temporal and topical signature of users' sharing behaviour, showing how they exhibit distinct behaviorial patterns on different networks. We also examine cross-sharing (i.e., the act of user broadcasting their activity to multiple OSNs near-simultaneously), a previously-unstudied behaviour and demonstrate how certain OSNs play the roles of originating source and destination sinks.
Personal Space in Virtual Reality

Improving the sense of ‘presence’ is a common goal of 3D display technology for film, television and virtual reality. However, there are instances in which 3D presentation may elicit unanticipated negative responses. For example, it is well established that violations of interpersonal space cause discomfort in real-world situations. Here we ask if people respond similarly when viewing life-sized stereoscopic images. Observers rated their level of comfort in response to animate and inanimate objects in live and virtual (stereoscopic projection) viewing conditions. Electrodermal activity was also recorded to monitor their physiological response to these stimuli. Subjects exhibited significant negative reactions to violations of interpersonal space in stereoscopic 3D displays, which were equivalent to those experienced in the natural environment. These data have important implications for the creation of 3D media and the use of virtual reality systems.
Deferasirox in Indian children with thalassemia major: 3 years experience

Abstract Objective: To evaluate the efficacy and safety of the oral iron chelator deferasirox in treating transfusional hemosiderosis in a cohort of Indian children with thalassemia major with high iron load. Materials and Methods: The first 50 children (age 2-18 yrs) with thalassemia major to commence deferasirox at our center were enrolled and followed up for a period of 36 months between April 2008 and March 2011. The dose of deferasirox was determined by their baseline serum ferritin and was adjusted to a maximum of 40 mg/kg/day depending on response. Ferritin levels, SGOT, SGPT, serum creatinine and urine albumin were regularly monitored. Results: Of the 50 patients, 76% documented a significant decline in serum ferritin ( P<0.05). Seven (14%) patients had a stable ferritin whilst 5 patients (10%) documented an increase over the study period. The mean serum ferritin at baseline, 12, 24 and 36 months was 4354, 3260, 3290 and 3042, respectively ( P<0.05). The median serum ferritin at the same time points was 3555, 2810, 2079 and 2271, respectively ( P<0.05). No severe toxicity was seen. Conclusions: Deferasirox, when given in doses ≥30 mg/kg, was found to be an effective and safe drug in reducing transfusional hemosiderosis. Thirty five (70%) needed dose escalation upto 40 mg/kg/day. Fifteen (30%), however did not achieve a negative iron balance despite maximally permissible doses.
Importance of Glycolysis for the Energetics of Anoxia‐Tolerant and Anoxia‐Intolerant Teleost Hepatocytes

The importance of glycolysis, as an ATP‐producing and substrate‐providing pathway, was studied in anoxia‐tolerant (goldfish) and anoxia‐intolerant (trout) hepatocytes. Inhibition of glycolysis with iodoacetic acid (IAA) left aerobic ATP production largely unaffected in hepatocytes from both species but caused a significant decrease of ATP contents in the goldfish cells. Ouabain‐sensitive oxygen consumption (osV̇o2), an estimate of mitochondrial ATP production coupled to ATP consumption by the Na+ pump, was significantly reduced in IAA‐treated goldfish hepatocytes, whereas it was unaltered in trout hepatocytes. Partial reduction of mitochondrial respiration, achieved by titration with cyanide (CN), strongly stimulated glycolytic flux but did not affect ATP contents of hepatocytes from both species. Under these conditions, osV̇o2 became undetectable. Rb+‐uptake rates, providing a direct estimate of Na+‐pump activity, were in good agreement with estimates derived from osV̇o2 in IAA‐treated cells, showing a decrease in goldfish and no change in trout. However, they indicated persistent Na+‐pump activity despite the lack of osV̇o2 in CN‐treated cells. Overall, these data indicate that in goldfish hepatocytes Na+‐pump activity is more dependent on glycolytic ATP production as compared to trout hepatocytes. Protein synthesis of goldfish hepatocytes was inhibited in IAA‐ and CN‐treated cells, possibly reflecting the hierarchical organization of energy metabolism. In trout hepatocytes, protein synthesis could be sustained at control levels, given that energetic substrate provision was not limited.
Mesotherapy versus Systemic Therapy in the Treatment of Acute Low Back Pain: A Randomized Trial

Pharmacological therapy of back pain with analgesics and anti-inflammatory drugs is frequently associated with adverse effects, particularly in the elderly. Aim of this study was to compare mesotherapic versus conventional systemic administration of nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids in patients with acute low back pain. Eighty-four patients were randomized to receive anti-inflammatory therapy according to the following protocols: (a) mesotherapy group received the 1st and 4th day 2% lidocaine (1 mL) + ketoprofen 160 mg (1 mL) + methylprednisolone 40 mg (1 mL), then on 7th, 10th, and 13th day, 2% lidocaine (1 mL) + ketoprofen 160 mg (1 mL) + methylprednisolone 20 mg (1 mL) (b) conventional therapy group received ketoprofen 80 mg × 2/die and esomeprazole 20 mg/die orally for 12 days, methylprednisolone 40 mg/die intramuscularly for 4 days, followed by methylprednisolone 20 mg/die for 3 days, and thereafter, methylprednisolone 20 mg/die at alternate days. Pain intensity and functional disability were assessed at baseline (T0), at the end of treatment (T1), and 6 months thereafter (T2) by using visual analogic scale (VAS) and Roland-Morris disability questionnaire (RMDQ). In both groups, VAS and RMDQ values were significantly reduced at the end of drug treatment and after 6 months, in comparison with baseline. No significant differences were found between the two groups. This suggests that mesotherapy may be a valid alternative to conventional therapy in the treatment of acute low back pain with corticosteroids and NSAIDs.
Effect of Antecedent Hypertension and Follow-Up Blood Pressure on Outcomes After High-Risk Myocardial Infarction

The influence of blood pressure on outcomes after high-risk myocardial infarction is not well characterized. We studied the relationship between blood pressure and the risk of cardiovascular events in 14 703 patients with heart failure, left ventricular systolic dysfunction, or both after acute myocardial infarction in the Valsartan in Myocardial Infarction Trial. We assessed the relationship between antecedent hypertension and outcomes and the association between elevated (systolic: >140 mm Hg) or low blood pressure (systolic: <100 mm Hg) in 2 of 3 follow-up visits during the first 6 months and subsequent cardiovascular events over a median 24.7 months of follow-up. Antecedent hypertension independently increased the risk of heart failure (hazard ratio [HR]: 1.19; 95% CI: 1.08 to 1.32), stroke (HR: 1.27; 95% CI: 1.02 to 1.58), cardiovascular death (HR: 1.11; 95% CI: 1.01 to 1.22), and the composite of death, myocardial infarction, heart failure, stroke, or cardiac arrest (HR: 1.13; 95% CI: 1.06 to 1.21). While low blood pressure in the postmyocardial infarction period was associated with increased risk of adverse events, patients with elevated blood pressure (n=1226) were at significantly higher risk of stroke (adjusted HR: 1.64; 95% CI: 1.17 to 2.29) and combined cardiovascular events (adjusted HR: 1.14; 95% CI: 1.00 to 1.31). Six months after a high-risk myocardial infarction, elevated systolic blood pressure, a potentially modifiable risk factor, is associated with an increased risk of subsequent stroke and cardiovascular events. Whether aggressive antihypertensive treatment can reduce this risk remains unknown.
Similar Psychological Distance Reduces Temporal Discounting

People often prefer inferior options in the present even when options in the future are more lucrative. Five studies investigated whether decision making could be improved by manipulating construal level and psychological distance. In Studies 1a, 1b, and 2, temporal discounting was reduced when future rewards (trips to Paris) were construed at a relatively concrete level, thus inducing a similar level of construal to present rewards. By contrast, Studies 3 and 4 reduced temporal discounting by making present financial rewards more psychologically distant via a social proximity manipulation, and thus linked to a similar high level of construal as future rewards. These results suggest that people prefer the more lucrative option when comparing two intertemporal choices that are construed on a similar level instead of on a different level. Thus, changes in construal level and mental representations can be used to promote more desirable choices in economic decision making.
Treatment of severe esophageal Crohn's disease with thalidomide

by using enzyme immunoassay and recombinant immunoblot assay showed seroconversion of anti-HCV on a blood sample taken on August 14, compared with a previously negative sample taken on August 3. Quantitative reverse transcriptase polymerase chain reaction indicated an HCV RNA of 104,280 genome copies/ml. Serological markers for hepatitis A (IgM hepatitis A virus antibody) and hepatitis B (IgM hepatitis B core antibody, IgG hepatitis B core antibody, hepatitis B surface antigen antibody, and hepatitis B surface antigen) were negative. In mid-June 1998, the patient received, in his dormitory, a tattoo (approx. 53 3 in) on his right flank. The tattoo device, assembled by inmates, consisted of a small batterydriven electric motor connected to a sharpened guitar string that acted as the tattoo needle. Reportedly, the tattooist poured ball pen ink into a toothpaste cup and drew the ink into a fountain pen–sized barrel attached to the device. The ink flowed along the surface of the guitar string, which punctured the skin as it was driven by the motor. The patient could not tell if the needle had been cleaned or used on other persons. After the tattoo was done, he washed the needle with hot water and returned it to the tattooist. Reportedly, more than one tattooist was active in the prison. The patient denied ever injecting drugs. During the 6-month period before his illness, the patient reported no history of blood transfusion, oral or anal sex, body piercing, sharing shavers or toothbrushes, invasive medical procedures, or contact with persons having hepatitis. He had received other tattoos on his chest and back in 1996. No signs of injecting drug use such as needle marks and skin tracks or signs of body piercing were found during examination. We conclude that there is strong evidence of acute HCV transmission via tattooing in this patient because the exposure period is unambiguously defined through seroconversion, which is absent in previous similar case reports (3, 4). Tattooing in prison may present a substantial risk for transmission of HCV and other bloodborne pathogens caused by the use of improper equipment, sharing tattoo devices, lack of sterilization facilities, and the high prevalence of HCV infection among inmates. However, we do not imply a similar risk with commercial tattooing in the general community, where the prevalence of HCV infection is lower and hygiene conditions are expectedly better.
Dose-dependent in vitro effect of recombinant human DNase on rheological and transport properties of cystic fibrosis respiratory mucus.

Recombinant human deoxyribonuclease (rhDNase) has been demonstrated to reduce the viscosity of purulent cystic fibrosis (CF) respiratory mucus, to improve pulmonary function and to reduce the risk of respiratory tract infectious exacerbations, but its effect on mucus transportability has not so far been investigated. The dose-dependent effect of rhDNase was analysed in vitro on mucus transport rate (tr) by ciliary activity and by simulated cough (cough transport (ct)), as well as on mucus viscosity and surface properties. Purulent CF sputa (n = 15) were incubated for 30 min at 37 degrees C with either rhDNase at three different concentrations (final concentrations 0.2, 2 or 20 micrograms.ml-1 of mucus) or placebo. No significant dose-dependent effect of rhDNase on the mucociliary transport rate was observed when the samples wer statistically analysed together. However, in the larger group of mucus samples (n = 11) with a low initial mucociliary transport rate, the latter was improved at each rhDNase concentration (tr0.2 = 0.69, tr2 = 0.88 and tr20 = 0.87) as compared to placebo (trp = 0.58). In the smaller group of mucus samples (n = 4) with high initial transport rate, a decrease in mucociliary transport rate was observed, particularly at the highest concentration rhDNase assayed, i.e. 20 micrograms.ml-1 of mucus (tr20 = 0.58) as compared to placebo (trp = 0.86). The mucus cough transport was increased by rhDNase (ct0.2 = 25 mm, ct2 = 27.5 mm and ct20 = 31 mm) as compared to placebo (ctp = 23.5 mm). (ABSTRACT TRUNCATED AT 250 WORDS)
Implication of the SMN complex in the biogenesis and steady state level of the Signal Recognition Particle

Spinal muscular atrophy is a severe motor neuron disease caused by reduced levels of the ubiquitous Survival of MotoNeurons (SMN) protein. SMN is part of a complex that is essential for spliceosomal UsnRNP biogenesis. Signal recognition particle (SRP) is a ribonucleoprotein particle crucial for co-translational targeting of secretory and membrane proteins to the endoplasmic reticulum. SRP biogenesis is a nucleo-cytoplasmic multistep process in which the protein components, except SRP54, assemble with 7S RNA in the nucleolus. Then, SRP54 is incorporated after export of the pre-particle into the cytoplasm. The assembly factors necessary for SRP biogenesis remain to be identified. Here, we show that 7S RNA binds to purified SMN complexes in vitro and that SMN complexes associate with SRP in cellular extracts. We identified the RNA determinants required. Moreover, we report a specific reduction of 7S RNA levels in the spinal cord of SMN-deficient mice, and in a Schizosaccharomyces pombe strain carrying a temperature-degron allele of SMN. Additionally, microinjected antibodies directed against SMN or Gemin2 interfere with the association of SRP54 with 7S RNA in Xenopus laevis oocytes. Our data show that reduced levels of the SMN protein lead to defect in SRP steady-state level and describe the SMN complex as the first identified cellular factor required for SRP biogenesis.
Comparing Quasi-Experimental Designs and Structural Models for Policy Evaluation: The Case of a Reform of Lone Parental Welfare

This paper compares two different ways of doing policy evaluation: on the one hand, quasi-experimental methods (or "ex-post" evaluations) which exploit the introduction of a reform and identify its effect by comparing treated and untreated individuals; on the other hand, structural models (or "ex-ante" evaluations) which are based on economic theory and predict the effect of potential reforms by using the estimates of behavioural parameters. The comparison is carried out using an empirical case. In 1998, in Norway, a major welfare reform changed the rules of the most generous benefit for lone parents: it increased the amount of the benefit and introduced working requirements. Using a quasi-experimental evaluation approach, it is found a positive effect of the reform on lone mothers' employment. In this paper, I estimate a static structural model of work and welfare participation decisions and compare the results using the two different approaches. Despite the differences in the assumptions I make for the two models, results are fairly comparable.
Scatter Search Applied to the Inference of a Development Gene Network

Efficient network inference is one of the challenges of current-day biology. Its application to the study of development has seen noteworthy success, yet a multicellular context, tissue growth, and cellular rearrangements impose additional computational costs and prohibit a wide application of current methods. Therefore, reducing computational cost and providing quick feedback at intermediate stages are desirable features for network inference. Here we propose a hybrid approach composed of two stages: exploration with scatter search and exploitation of intermediate solutions with low temperature simulated annealing. We test the approach on the well-understood process of early body plan development in flies, focusing on the gap gene network. We compare the hybrid approach to simulated annealing, a method of network inference with a proven track record. We find that scatter search performs well at exploring parameter space and that low temperature simulated annealing refines the intermediate results into excellent model fits. From this we conclude that for poorly-studied developmental systems, scatter search is a valuable tool for exploration and accelerates the elucidation of gene regulatory networks.
Bose-Einstein Condensates in Superlattices

We consider the Gross--Pitaevskii (GP) equation in the presence of periodic and quasi-periodic superlattices to study cigar-shaped Bose--Einstein condensates (BECs) in such potentials. We examine spatially extended wavefunctions in the form of modulated amplitude waves (MAWs). With a coherent structure ansatz, we derive amplitude equations describing the evolution of spatially modulated states of the BEC. We then apply second-order multiple scale perturbation theory to study harmonic resonances with respect to a single lattice substructure as well as ultrasubharmonic resonances that result from interactions of both substructures of the superlattice. In each case, we determine the resulting system's equilibria, which represent spatially periodic solutions, and subsequently examine the stability of the corresponding wavefunctions by direct simulations of the GP equation, identifying them as typically stable solutions of the model. We then study subharmonic resonances using Hamiltonian perturbation theory, tracing robust spatio-temporally periodic patterns.
A Viterbi algorithm for a trajectory model derived from HMM with explicit relationship between static and dynamic features

This paper introduces a Viterbi algorithm to obtain a sub-optimal state sequence for trajectory-HMM, which is derived from HMM with explicit relationship between static and dynamic features. The trajectory-HMM can alleviate some limitations of HMM, which are (i) constant statistics within HMM state and (ii) conditional independence of observations given the state sequence, without increasing the number of model parameters. The proposed algorithm was applied to state-boundary optimization for Viterbi training and N-best rescoring. In a speaker-dependent continuous speech recognition experiment, trajectory-HMM with the proposed algorithm achieved about 14% error reduction over the standard HMM with the conventional Viterbi algorithm.