Miracle-dz/UniFAR-FTUs huggingface dataset:
The AtMYB12 activation domain maps to a short C-terminal region of the transcription factor

Abstract The Arabidopsis thaliana R2R3-MYB transcription factor MYB12 is a light-inducible, flavonol-specific activator of flavonoid biosynthesis. The transactivation activity of the AtMYB12 protein was analyzed using a C-terminal deletion series in a transient A. thaliana protoplast assay with the goal of mapping the activation domain (AD). Although the deletion of the last 46 C-terminal amino acids did not affect the activation capacity, the deletion of the last 98 amino acids almost totally abolished transactivation of two different target promoters. A domain swap experiment using the yeast GAL4 DNA-binding domain revealed that the region from positions 282 to 328 of AtMYB12 was sufficient for transactivation. In contrast to the R2R3-MYB ADs known thus far, that of AtMYB12 is not located at the rearmost C-terminal end of the protein. The AtMYB12 AD is conserved in other experimentally proven R2R3-MYB flavonol regulators from different species.
Correlating RNFL Thickness by OCT With Perimetric Sensitivity in Glaucoma Patients

PurposeTo determine whether a structure-function model developed for normal age-related losses of retinal ganglion cells also models the retinal ganglion cell losses in glaucomatous optic neuropathy. MethodsThe model to relate age-related loss of retinal nerve fiber layer thickness and reduced sensitivity for standard automated perimetry was evaluated with data from 30 glaucoma patients and 40 normal individuals. Perimetry thresholds were translated into separate retinal ganglion cell body estimates for test locations in the superior and inferior visual fields. The retinal nerve fiber layer thickness from optical coherence tomography was also divided into regions representing the superior and inferior hemifields to obtain estimates of the axons in each hemifield. The 2 estimates of retinal ganglion cell populations were compared for corresponding regions. ResultsAgreement between neural estimates was good for normal individuals and patients with early glaucomatous damage. Results for individuals with advanced glaucoma showed disparities between neural estimates that were proportional to the stage of disease. A correction factor for the stage of disease was introduced for the derivation of ganglion cell populations from the nerve fiber layer measurements, which produced agreement between the optical coherence tomography and perimetric estimates for all patients. ConclusionsThe modified structure-function model provided well-correlated relationships between the subjective measures of visual sensitivity and the objective measures of retinal nerve fiber layer thickness when parameters for the patient's age and the severity of the disease were included. The results suggest constitutive relationships between structure and function for the full spectrum of normal-to-advanced glaucomatous neuropathy.
Un turc mécanique pour les ressources linguistiques : critique de la myriadisation du travail parcellisé (Mechanical Turk for linguistic resources: review of the crowdsourcing of parceled work)

Cet article est une prise de position concernant les plate-formes de type Amazon Mechanical Turk, dont l’utilisation est en plein essor depuis quelques années dans le traitement automatique des langues. Ces plateformes de travail en ligne permettent, selon le discours qui prévaut dans les articles du domaine, de faire développer toutes sortes de ressources linguistiques de qualité, pour un prix imbattable et en un temps très réduit, par des gens pour qui il s’agit d’un passe-temps. Nous allons ici démontrer que la situation est loin d’être aussi idéale, que ce soit sur le plan de la qualité, du prix, du statut des travailleurs ou de l’éthique. Nous rappellerons ensuite les solutions alternatives déjà existantes ou proposées. Notre but est ici double : informer les chercheurs, afin qu’ils fassent leur choix en toute connaissance de cause, et proposer des solutions pratiques et organisationnelles pour améliorer le développement de nouvelles ressources linguistiques en limitant les risques de dérives éthiques et légales, sans que cela se fasse au prix de leur coût ou de leur qualité.
The EU's Comprehensive Approach to Security: A Culture of Co-ordination?

From the 1990s onwards, the concept of security has changed fundamentally. Security does not only mean avoiding an unwilling form of death, it has to do with management of life and its social and structural conditions (Bigo and Tsoukala 2008). The so-called security and development nexus linked human development, human rights and transnational responsibility with ensuing consequences for how threats to security are addressed (Hettne, 2010). Approaching security questions comprehensively is now in high demand. The operations in Bosnia, Kosovo, Afghanistan and Iraq have made it clear that military intervention needs to go hand-in-hand with reconstruction, nation-building and development in order to reach stable and self-sustainable social and economic structures. The initial phase was mastered relatively well by the international community, but it is the second phase, aimed at sustainable peace, which necessitates a whole new concept of crisis-management. When the European Union, in 1999, gained a security and defence dimension with the European Security and Defence Policy (ESDP, now CSDP) it seemed particularly wellsuited to take on these challenges.
MPPT Control of Wind Generation Systems Based on Estimated Wind Speed Using SVR

In this paper, a novel algorithm for wind-speed estimation in wind-power generation systems is proposed, which is based on the theory of support-vector regression (SVR). The inputs of the SVR wind-speed estimator are chosen as the wind-turbine power and rotational speed. During the offline training, a specified model, which relates the inputs to the output, is obtained. Then, the wind speed is determined online from the instantaneous inputs. The experimental results have verified the validity of the proposed estimation algorithm.
Obesity and physical inactivity in rural America.

CONTEXT AND PURPOSE Obesity and physical inactivity are common in the United States, but few studies examine this issue within rural populations. The present study uses nationally representative data to study obesity and physical inactivity in rural populations. METHODS Data came from the 1998 National Health Interview Survey Sample Adult and Adult Prevention Module. Self-reported height and weight were used to calculate body mass index. Physical inactivity was defined using self-reported leisure-time physical activity. Analyses included descriptive statistics, chi 2 tests, and logistic regression. FINDINGS Obesity was more common among rural (20.4%, 95% CI 19.2%-21.6%) than urban adults (17.8%, 95% CI 17.2%-18.4%). Rural residents of every racial/ethnic group were at higher risk of obesity than urban whites, other factors held equal. Other predictors of obesity included being male, age 25-74, lacking a high school diploma, having physical limitations, fair to poor health, and a history of smoking. Proportionately more rural adults were physically inactive than their urban peers (62.8% versus 59.3%). Among rural residents, minorities were not significantly more likely to be inactive than whites. Males and younger adults were less likely to be inactive. Rural adults who were from the Midwest and South, had less than a high school education, had fair to poor health, and currently smoked were more likely to be inactive compared to their respective referent group. CONCLUSIONS The high prevalence of obesity and inactive lifestyles among rural populations call for research into effective rural interventions.
Homologous recombination enhancement conferred by the Z-DNA motif d(TG)30 is abrogated by simian virus 40 T antigen binding to adjacent DNA sequences

The Z-DNA motif polydeoxythymidylic-guanylic [d(TG)]. polydeoxyadenylic-cytidylic acid [d(AC)], present throughout eucaryotic genomes, is capable of readily forming left-handed Z-DNA in vitro and has been shown to promote homologous recombination. The effects of simian virus 40 T-antigen-dependent substrate replication upon the stimulation of recombination conferred by the Z-DNA motif d(TG)30 were analyzed. Presence of d(TG)30 adjacent to a T-antigen-binding site I can stimulate homologous recombination between nonreplicating plasmids, providing that T antigen is absent, in both simian CV-1 cells and human EJ cells (W. P. Wahls, L. J. Wallace, and P. D. Moore, Mol. Cell. Biol. 10:785-793). It has also been shown elsewhere that the presence of d(TG)n not adjacent to the T-antigen-binding site can stimulate homologous recombination in simian virus 40 molecules replicating in the presence of T antigen (P. Bullock, J. Miller, and M. Botchan, Mol. Cell. Biol. 6:3948-3953, 1986). However, it is demonstrated here that d(TG)30 nine base pairs distant from a T-antigen-binding site bound with T antigen does not stimulate recombination between either replicating or nonreplicating substrates in somatic cells. The bound T antigen either prevents the d(TG)30 sequence from acquiring a recombinogenic configuration (such as left-handed Z-DNA), or it prevents the interaction of recombinase proteins with the sequence by stearic hindrance.
Trends in Tuberculosis Mortality in the United States, 1990–2006: A Population-Based Case-Control Study

Objective. We assessed demographic and temporal trends of tuberculosis (TB)-related deaths in the United States and examined associated comorbidities listed on death certificates. Methods. We analyzed TB-related mortality from 1990 through 2006 by examining multiple-cause-of-death data from the National Center for Health Statistics. We assessed age-adjusted mortality rates, secular trends, associations with demographic variables, and comorbid conditions. Results. From 1990 through 2006, TB was reported as a cause of death among 53,505 people in the U.S. with a combined overall mean age-adjusted mortality rate of 1.16 per 100,000 person-years. The age-adjusted TB mortality rate declined from 2.22 per 100,000 person-years in 1990 to 0.47 per 100,000 person-years in 2006, demonstrating mean annual decline of about 10%. People aged 75 years and older; males; foreign-born people; and those of Hispanic, Asian, black, and Native American race/ethnicity had comparatively elevated TB-related mortality rates. The mortality rate in foreign-born people was more than two times higher than in U.S.-born people. About 89% of deaths among people of Asian race/ethnicity and nearly 50% among black people were foreign-born individuals. Human immunodeficiency virus and selected autoimmune diseases were more common in TB-related deaths. Conclusions. TB mortality decreased substantially from 1990 through 2006, but remains an important cause of preventable mortality. The observed decrease was more pronounced among U.S.-born people than among foreign-born people. Disparities in TB-related mortality and the identification of important comorbid conditions can inform strategies targeting subpopulations at increased risk for fatal TB infection.
Insulin analogues: an example of applied medical science

Insulin analogues were developed to try and achieve more physiological insulin replacement from injection in the subcutaneous site. Their pharmacokinetics and pharmacodynamics differ from human insulin when injected subcutaneously because of alterations in the amino acid sequence of the insulin molecule. The rapid‐acting insulin analogues, lispro, aspart and glulisine, have a rapid onset of action and shorter duration of action because of changes to the B26–30 portion of insulin inhibiting formation of dimers and hexamers. They appear to improve postprandial glucose, incidence of hypoglycaemia and patient satisfaction and, when used in combination with basal insulin analogues, improve glycosylated haemoglobin in comparison to conventional insulin therapy. Additionally, they have been successfully used in children, pregnant women, in pump therapy and as part of premixed biphasic regimens. The two basal insulin analogues, glargine and detemir, developed by adjusting the isoelectric point and adding a fatty acid residue, respectively, have a protracted duration of action and a relatively smooth profile. Their pharmacokinetic and pharmacodynamic profiles have been assessed using euglycaemic clamp protocols. Both analogues have a longer duration of action, less of a peak of activity and a reduced variability with repeated injection. There is some evidence to suggest that detemir may have a slight hepatoselective effect. Clinical studies have shown a lower relative risk of hypoglycaemia and detemir appears to have a weight‐sparing action. Insulin analogues represent a successful example of applied medical science.
A Randomized, Double-Blinded, Clinical Trial on Effects of a Vitis vinifera Extract on Cognitive Function in Healthy Older Adults

Introduction: Gradual population aging is creating a new set of needs in the general population. Memory capacity decreases with age, and memory deficits are considered an early symptom of Alzheimer’s Disease (AD), one of the most prevalent cognitive disorders in older people. Numerous studies have shown that grape polyphenolic compounds (GPs) are able to attenuate cognitive impairment and reduce brain lesions in experimental AD animal models. These GP effects are associated with improvement in brain antioxidant status and prevention of free radical-induced neuronal damage. We designed a randomized, double-blind, placebo-controlled clinical trial to investigate the potential beneficial effects of a Vitis vinifera-based dietary supplement on cognitive function and neuropsychological status in healthy older adults. Methods: One-hundred eleven subjects were recruited and randomly divided in two groups: one group received the V. vinifera-based dietary supplement Cognigrape® for 12 weeks (250 mg/day) and the second group received placebo over the same period of time. Before and after the end of the supplementation period, cognitive function and neuropsychological status were evaluated using the Mini-Mental State Examination (MMSE), Beck Depression Inventory (BDI), Hamilton Anxiety Rating Scale (HARS), and Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) evaluations. Results: MMSE scores were significantly improved after supplementation with Cognigrape® in comparison with baseline levels (p < 0.0001) and placebo (r = 0.59, 0.95% CI 0.11, 1.22; p < 0.0001). Cognigrape® supplementation produced a significant reduction in BDI (-15.8%) and HARS (-24.9%) scores with respect to baseline levels (p < 0.0001) and placebo (p < 0.0001 for BDI and p < 0.05 for HARS). RBANS total score was significantly improved by Cognigrape® with respect to baseline levels and placebo (r = 0.55, 0.95% CI 0.48, 6.07; p < 0.0001). The comparison with the placebo revealed improvements in several parameters among participants receiving Cognigrape®: attention (p < 0.001); language (p < 0.05); immediate memory (p < 0.0001); and delayed memory (p < 0.0001). Visuospatial/constructional abilities were not modified. During the study, no adverse effects were detected. Conclusion: The results show that 12 weeks of Cognigrape® supplementation is safe, can improve physiological cognitive profiles, and can concurrently ameliorate negative neuropsychological status in healthy older adults.
The RhoJ-BAD signaling network: An Achilles’ heel for BRAF mutant melanomas

Genes and pathways that allow cells to cope with oncogene-induced stress represent selective cancer therapeutic targets that remain largely undiscovered. In this study, we identify a RhoJ signaling pathway that is a selective therapeutic target for BRAF mutant cells. RhoJ deletion in BRAF mutant melanocytes modulates the expression of the pro-apoptotic protein BAD as well as genes involved in cellular metabolism, impairing nevus formation, cellular transformation, and metastasis. Short-term treatment of nascent melanoma tumors with PAK inhibitors that block RhoJ signaling halts the growth of BRAF mutant melanoma tumors in vivo and induces apoptosis in melanoma cells in vitro via a BAD-dependent mechanism. As up to 50% of BRAF mutant human melanomas express high levels of RhoJ, these studies nominate the RhoJ-BAD signaling network as a therapeutic vulnerability for fledgling BRAF mutant human tumors.
Modeling the impact of HIV chemoprophylaxis strategies among men who have sex with men in the United States: HIV infections prevented and cost-effectiveness

Background and objective:HIV chemoprophylaxis may be a future prevention strategy to help control the global epidemic of HIV/AIDS. Safety and efficacy trials of two agents are currently underway. We assess the expected number of HIV cases prevented and cost-effectiveness of a hypothetical HIV chemoprophylaxis program among men who have sex with men in a large US city. Design and methods:We developed a stochastic compartmental mathematical model using HIV/AIDS surveillance data to simulate the HIV epidemic and the impact of a 5-year chemoprophylaxis program under varying assumptions for epidemiological, behavioral, programmatic and cost parameters. We estimated program effectiveness and costs from the perspective of the US healthcare system compared with current HIV prevention practices. The main outcome measures were number of HIV infections prevented and incremental cost per quality-adjusted life-years saved. Results:A chemoprophylaxis program targeting 25% of high-risk men who have sex with men in New York City could prevent 780 (4%) to 4510 (23%) of the 19 510 HIV infections predicted to occur among all men who have sex with men in New York City in 5 years. More than half of prevented infections would be among those not taking chemoprophylaxis but who benefit from reduced HIV prevalence in the community. Under base-case assumptions, incremental cost was US$ 31 970 per quality-adjusted life-years saved. The program was cost-effective under most variations in efficacy, mechanism of protection and adherence. Conclusion:HIV chemoprophylaxis among high-risk men who have sex with men in a major US city could prevent a significant number of HIV infections and be cost-effective.
Production and Evaluation of Specific Single-Chain Antibodies against CTLA-4 for Cancer-Targeted Therapy.

BACKGROUND Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) molecules are expressed on T-cells and inhibit their function by inhibiting activation of subsequent T-cell molecular pathways. Blocking of CTLA-4 inhibits the growth of malignant tumor cells. Anti-CTLA-4 monoclonal antibodies activate the immune system against cancer. Due to several advantages of single-chain antibodies (scFvs) compared to monoclonal antibodies in cancer immunotherapy, specific anti-CTLA-4 scFvs (single-chain variable fragment) were selected in this study. METHODS A phage antibody display library of scFvs was analyzed and a panning process was performed against an immunodominant epitope of CTLA-4. PCR and DNA fingerprinting were used to differentiate the specific clones. The specificity of the selected clones was investigated by phage ELISA (Enzyme-linked immunosorbent assay). RESULTS Two specific clones with frequencies of 35 and 20% were identified. The clones reacted with the corresponding epitope on ELISA, while no reactivity was observed with an unrelated peptide, M13KO7 helper phage, unrelated scFvs, or no peptide as negative controls. CONCLUSION Targeted therapy against cancer markers is an ideal treatment strategy. Specific human anti-CTLA-4scFvs were selected in this study. These scFvs bound the related epitope. These antibodies have the potential to be used for targeted therapy, where the blocking of CTLA4 receptor is needed. The study suggests further evaluation of the selected scFvs to reveal the effects of the selected antibodies.
Regulation of the Urokinase Receptor by Its Plasminogen Activator

Summary There is now ample evidence that the proteolytic action of urokinase (UK) is potentiated by a specific cell surface receptor. The present study was undertaken to assess the role of UK as a modulator of its receptor. GEO colonic cells, which secrete relatively low levels of UK (≃0.1 nM/72 h per 106 cells) and display approximately 104 receptors per cell, 10% of which are "tagged" with the endogenous plasminogen activator (PA), was selected for the study. A 90% reduction in the specific binding of radioactive DFP-UK was observed for cells cultivated in the presence of two-chain (TC) UK (M r 55,000). This only partly reflected occupation of the receptors with UK supplied in the culture medium, since the specific binding of the radioligand was still reduced by 60% after an acid pretreatment, which dissociates receptor-bound UK. The reduction in radioactive DFP-UK binding to cells treated with high molecular weight UK, either in the single or two-chain form, was both concentration and time dependent. Maximum reductions (70%) were achieved by treatment of the cells for 24 h with 1 nM of the plasminogen activator. In contrast, low molecular weight UK, which lacks part of the UK A chain, had no effect on ligand binding. Attenuation of radioactive DFP-UK binding to UK treated GEO cells was a consequence of a 60% reduction in the number of binding sites. Treatment of GEO cells with an antibody, which blocks the binding of endogenous UK to its receptor, augmented radioactive DFP-UK binding by two-fold. These data indicate that for one colonic cell line, at least, UK down-regulates its own binding site subsequent to it being bound to the receptor.
Using physician billing claims from the Ontario Health Insurance Plan to determine individual influenza vaccination status: an updated validation study.

BACKGROUND Owing to the absence of a vaccination registry in Ontario, administrative data are currently the best available source to determine population-based individual-level influenza vaccination status. Our objective was to validate physician billing claims for influenza vaccination in the Ontario Health Insurance Plan database against the Canadian Community Health Survey. METHODS We used self-reported seasonal influenza vaccination status of Ontario residents surveyed between 2007 and 2009 as the reference standard. The survey responses were linked to physician claims database records to validate billing codes for influenza vaccination. We calculated sensitivity, specificity, positive predictive value and negative predictive value with 95% confidence intervals (CIs). We stratified the data by several covariates and comorbidities to determine stratum-specific performance characteristics. We used these estimates to adjust an estimate of influenza vaccine effectiveness for the 2010/11 influenza season. RESULTS For the 47 301 patients included in the analysis, the sensitivity for the billing codes was 49.8% (95% CI 49.0%-50.5%), specificity was 95.7% (95% CI 95.5%-96.0%), positive predictive value was 88.4% (95% CI 87.8%-89.0%) and negative predictive value was 74.5% (95% CI 74.0%-74.9%). Performance measures were optimized in patients aged 65 years and older, particularly those with comorbidities. INTERPRETATION Although administrative data have limitations for determining influenza vaccination status, owing to the high positive predictive value, they are well suited for self-controlled study designs that are often used to assess vaccine safety. For studies of coverage and effectiveness, restricting the cohort to patients aged 65 years and older will minimize misclassification bias. Performance characteristics from this study can be used to mitigate misclassification bias.