Surface patterning of polyacrylamide gel using scanning electrochemical cell microscopy (SECCM)

Scanning electrochemical cell microscopy is introduced as a new tool for the synthesis and deposition of polymers on SAM-functionalised Au surfaces. The deposition of poly(N-hydroxyethyl acrylamide) is shown to be enhanced through the electrochemical generation of activating Cu(I)Cl/Me6TREN catalyst. Initiation of the polymerisation reaction is most likely due to in situ generation of reactive oxygen species following oxygen reduction

Leukotriene antagonists as first-line or add-on asthma controller therapy

Most randomized trials of treatment for asthma study highly selected patients under idealized conditions. METHODS: We conducted two parallel, multicenter, pragmatic trials to evaluate the real-world effectiveness of a leukotriene-receptor antagonist (LTRA) as compared with either an inhaled glucocorticoid for first-line asthma-controller therapy or a long-acting beta(2)-agonist (LABA) as add-on therapy in patients already receiving inhaled glucocorticoid therapy. Eligible primary care patients 12 to 80 years of age had impaired asthma-related quality of life (Mini Asthma Quality of Life Questionnaire [MiniAQLQ] score =6) or inadequate asthma control (Asthma Control Questionnaire [ACQ] score =1). We randomly assigned patients to 2 years of open-label therapy, under the care of their usual physician, with LTRA (148 patients) or an inhaled glucocorticoid (158 patients) in the first-line controller therapy trial and LTRA (170 patients) or LABA (182 patients) added to an inhaled glucocorticoid in the add-on therapy trial. RESULTS: Mean MiniAQLQ scores increased by 0.8 to 1.0 point over a period of 2 years in both trials. At 2 months, differences in the MiniAQLQ scores between the two treatment groups met our definition of equivalence (95% confidence interval [CI] for an adjusted mean difference, -0.3 to 0.3). At 2 years, mean MiniAQLQ scores approached equivalence, with an adjusted mean difference between treatment groups of -0.11 (95% CI, -0.35 to 0.13) in the first-line controller therapy trial and of -0.11 (95% CI, -0.32 to 0.11) in the add-on therapy trial. Exacerbation rates and ACQ scores did not differ significantly between the two groups. CONCLUSIONS: Study results at 2 months suggest that LTRA was equivalent to an inhaled glucocorticoid as first-line controller therapy and to LABA as add-on therapy for diverse primary care patients. Equivalence was not proved at 2 years. The interpretation of results of pragmatic research may be limited by the crossover between treatment groups and lack of a placebo group

Drosophila eiger Mutants Are Sensitive to Extracellular Pathogens

We showed previously that eiger, the Drosophila tumor necrosis factor homolog, contributes to the pathology induced by infection with Salmonella typhimurium. We were curious whether eiger is always detrimental in the context of infection or if it plays a role in fighting some types of microbes. We challenged wild-type and eiger mutant flies with a collection of facultative intracellular and extracellular pathogens, including a fungus and Gram-positive and Gram-negative bacteria. The response of eiger mutants divided these microbes into two groups: eiger mutants are immunocompromised with respect to extracellular pathogens but show no change or reduced sensitivity to facultative intracellular pathogens. Hence, eiger helps fight infections but also can cause pathology. We propose that eiger activates the cellular immune response of the fly to aid clearance of extracellular pathogens. Intracellular pathogens, which can already defeat professional phagocytes, are unaffected by eiger

Peptide exchange on MHC-I by TAPBPR is driven by a negative allostery release cycle.

Chaperones TAPBPR and tapasin associate with class I major histocompatibility complexes (MHC-I) to promote optimization (editing) of peptide cargo. Here, we use solution NMR to investigate the mechanism of peptide exchange. We identify TAPBPR-induced conformational changes on conserved MHC-I molecular surfaces, consistent with our independently determined X-ray structure of the complex. Dynamics present in the empty MHC-I are stabilized by TAPBPR and become progressively dampened with increasing peptide occupancy. Incoming peptides are recognized according to the global stability of the final pMHC-I product and anneal in a native-like conformation to be edited by TAPBPR. Our results demonstrate an inverse relationship between MHC-I peptide occupancy and TAPBPR binding affinity, wherein the lifetime and structural features of transiently bound peptides control the regulation of a conformational switch located near the TAPBPR binding site, which triggers TAPBPR release. These results suggest a similar mechanism for the function of tapasin in the peptide-loading complex

Francisella tularensis in the United States

Subpopulations A.I and A.II. of Francisella tularensis subsp. tularensis are associated with unique biotic and abiotic factors that maintain disease foci

Eff ect of antenatal multiple micronutrient supplementation on anthropometry and blood pressure in mid-childhood in Nepal: follow-up of a double-blind randomised controlled trial

Background In 2002–04, we did a randomised controlled trial in southern Nepal, and reported that children born to mothers taking multiple micronutrient supplements during pregnancy had a mean birthweight 77 g greater than children born to mothers taking iron and folic acid supplements. Children born to mothers in the study group were a mean 204 g heavier at 2·5 years of age and their systolic blood pressure was a mean 2·5 mm Hg lower than children born to mothers in the control group. We aimed to follow up the same children to mid-childhood (age 8·5 years) to investigate whether these diff erences would be sustained. Methods For this follow-up study, we identifi ed children from the original trial and measured anthropometry, body composition with bioelectrical impedance (with population-specifi c isotope calibration), blood pressure, and renal dimensions by ultrasound. We documented socioeconomic status, household food security, and air pollution. Main outcomes of the follow-up at 8 years were Z scores for weight-for-age, height-for-age, and body-mass index (BMI)-forage according to WHO Child Growth Standards for children aged 5–19 years, and blood pressure. This study is registered with the International Standard Randomised Controlled Trial register, number ISRCTN88625934. Findings Between Sept 21, 2011, and Dec 7, 2012, we assessed 841 children (422 in the control group and 419 in the intervention group). Unadjusted diff erences (intervention minus control) in Z scores were 0·05 for weight-for-age (95% CI –0·09 to 0·19), 0·02 in height-for-age (–0·10 to 0·15), and 0·04 in BMI-for-age (–0·09 to 0·18). We recorded no diff erence in blood pressure. Adjusted diff erences were similar for all outcomes. Interpretation We recorded no diff erences in phenotype between children born to mothers who received antenatal multiple micronutrient or iron and folate supplements at age 8·5 years. Our fi ndings did not extend to physiological diff erences or potential longer-term eff ects

PLM adoption in SMEs context

The increasing market needs and technologies evolution, push companies to develop competitive advantages based on adequate and intensive use of information technology and communication (ICT). However, SMEs do not realize the importance of ICT adoption, which becomes vital for the development, and are not always well equipped to adopt and integrate them to their activities. The paper focused on issues regarding the ICT adoption, especially PLM solutions by SMEs. By analyzing the PLM definitions and works done, we explored indicators that impact positively or negatively ICT and PLM adoption. This paper proposes a model, currently theoretical, with empirical validation proposal through a survey

It Takes Two

Theories of conflict emphasize dyadic interaction, yet existing empirical studies of civil war focus largely on state attributes and pay little attention to nonstate antagonists. We recast civil war in a dyadic perspective, and consider how nonstate actor attributes and their relationship to the state influence conflict dynamics. We argue that strong rebels, who pose a military challenge to the government, are likely to lead to short wars and concessions. Conflicts where rebels seem weak can become prolonged if rebels can operate in the periphery so as to defy a government victory yet are not strong enough to extract concessions. Conflicts should be shorter when potential insurgents can rely on alternative political means to violence. We examine these hypotheses in a dyadic analysis of civil war duration and outcomes, using new data on nonstate actors and conflict attributes, finding support for many of our conjectures. </jats:p