765 research outputs found
Evaporative gold nanorod assembly on chemically stripe-patterned gradient surfaces
Experimentally we explore the potential of using pre-defined motion of a receding contact line to control the deposition of nanoparticles from suspension. Stripe-patterned wettability gradients are employed, which consist of alternating hydrophilic and hydrophobic stripes with increasing macroscopic surface energy. Nanoparticle suspensions containing nanorods and nanospheres are deposited onto these substrates and left to dry. After moving over the pattern and evaporation of the solvent, characteristic nanoparticle deposits are found. The liquid dynamics has a pronounced effect on the spatial distribution. Nanoparticles do not deposit on the hydrophobic regions; there is high preference to deposit on the wetting stripes. Moreover, the fact that distributed nanoparticle islands are formed suggests that the receding of the contact line occurs in a stick-slip like fashion. Furthermore, the formation of liquid bridges covering multiple stripes during motion of the droplet over the patterns is modeled. We discuss their origin and show that the residue after drying, containing both nanoparticles and the stabilizing surfactant, also resembles such dynamics. Finally, zooming into individual islands reveals that highly selective phase separation occurs based on size and shape of the nanoparticle
Increased usage of special educational services by children born to mothers with systemic lupus erythematosus and antiphospholipid antibodies
Introduction: Surveys of long-term health and
developmental outcomes of children born to mothers
with systemic lupus erythematosus (SLE) have
suggested an increase in learning disabilities among
these children. We performed this observational study
to investigate the relationship between maternal
autoantibodies and antiphospholipid antibody
syndrome (APS) in maternal lupus patients and
neurocognitive development among their offspring.
Methods: SLE mothers with at least one live birth
postlupus diagnosis were enrolled. Data on maternal
medical/obstetric history and children’s perinatal/
medical history were collected by structured interview
and medical record reviews. The primary outcome was
requirement for special educational (SE) services,
a proxy for developmental delays. Multiple logistic
regression modelling was used to examine
associations between APS and autoantibodies with SE
usage, accounting for SLE disease severity and
potential confounders.
Results: Data on 38 mothers and 60 offspring were
analysed: SE service usage was reported for 15 of 60
(25%) offspring. Maternal APS history was
significantly associated with increased use of SE
services among offspring, including after adjustment
for lupus anticoagulant (LA) positivity and potential
confounders (OR 5.5–9.4 for delays age ≥2; p<0.05).
The presence of LA, but not other antiphospholipid
antibodies, was also associated with increased SE
services usage.
Conclusions: Maternal APS and LA were
independently associated with increased usage of
special educational services among offspring of
women with SLE.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/108201/1/Lupus Sci Med-2014-Marder-.pdf5
Chronic destructive arthritis as an isolated symptom of familial Mediterranean fever (FMF) in a 17 year old Turkish boy
Sociocultural Competence Training in Higher Engineering Education: The Role of Gaming Simulation
The present study focuses on competency-based approach in higher engineering education. Today engineers are required to be socially, culturally and communicatively skilled and able to act in constantly changing sociocultural environment. Presently the development of engineers’ sociocultural competency is of great importance, which is seen from the criteria for accrediting engineering programs of numerous international organizations, e.g. ABET. The paper presents some methods of sociocultural competency training based on the techniques of gaming simulation. Here we describe the educational games “Intercultural communication” and “The art of presentation” for the students of Elite Education Department of National Research Tomsk Polytechnic University. The results of incorporating the gaming technologies in education contribute to the effectiveness of engineers’ sociocultural competency training. The paper ends by pointing out gaming simulation which is a cutting-edge pedagogical approach which allows students to participate in realistic scenarios and develop sociocultural competency
Rhesus TRIM5α disrupts the HIV-1 capsid at the inter-hexamer interfaces
TRIM proteins play important roles in the innate immune defense against retroviral infection, including human immunodeficiency virus type-1 (HIV-1). Rhesus macaque TRIM5α (TRIM5αrh) targets the HIV-1 capsid and blocks infection at an early post-entry stage, prior to reverse transcription. Studies have shown that binding of TRIM5α to the assembled capsid is essential for restriction and requires the coiled-coil and B30.2/SPRY domains, but the molecular mechanism of restriction is not fully understood. In this study, we investigated, by cryoEM combined with mutagenesis and chemical cross-linking, the direct interactions between HIV-1 capsid protein (CA) assemblies and purified TRIM5αrh containing coiled-coil and SPRY domains (CC-SPRYrh). Concentration-dependent binding of CC-SPRYrh to CA assemblies was observed, while under equivalent conditions the human protein did not bind. Importantly, CC-SPRYrh, but not its human counterpart, disrupted CA tubes in a non-random fashion, releasing fragments of protofilaments consisting of CA hexamers without dissociation into monomers. Furthermore, such structural destruction was prevented by inter-hexamer crosslinking using P207C/T216C mutant CA with disulfide bonds at the CTD-CTD trimer interface of capsid assemblies, but not by intra-hexamer crosslinking via A14C/E45C at the NTD-NTD interface. The same disruption effect by TRIM5αrh on the inter-hexamer interfaces also occurred with purified intact HIV-1 cores. These results provide insights concerning how TRIM5α disrupts the virion core and demonstrate that structural damage of the viral capsid by TRIM5α is likely one of the important components of the mechanism of TRIM5α-mediated HIV-1 restriction. © 2011 Zhao et al
Styrene-Associated Health Outcomes at a Windblade Manufacturing Plant
Background: Health risks of using styrene to manufacture windblades for the green energy sector are unknown.
Methods: Using data collected from 355 (73%) current windblade workers and regression analysis, we investigated associations between health outcomes and styrene exposure estimates derived from urinary styrene metabolites.
Results: The median current styrene exposure was 53.6 mg/g creatinine (interquartile range: 19.5–94.4). Color blindness in men and women (standardized morbidity ratios 2.3 and 16.6, respectively) was not associated with exposure estimates, but was the type previously reported with styrene. Visual contrast sensitivity decreased and chest tightness increased (odds ratio 2.9) with increasing current exposure. Decreases in spirometric parameters and FeNO, and increases in the odds of wheeze and asthma-like symptoms (odds ratios 1.3 and 1.2, respectively) occurred with increasing cumulative exposure.
Conclusions: Despite styrene exposures below the recommended 400 mg/g creatinine, visual and respiratory effects indicate the need for additional preventative measures in this industry
Mercury Exposure and Antinuclear Antibodies among Females of Reproductive Age in the United States: NHANES
Background: Immune dysregulation associated with mercury has been suggested, though data in the general population are lacking. Chronic exposure to low levels of methylmercury (organic) and inorganic mercury is common, such as through fish consumption and dental amalgams.
Objective: To examine associations between mercury biomarkers and antinuclear antibody (ANA) positivity and titer strength.
Methods: Among females 16-49 years (n=1352) from the National Health and Nutrition Examination Survey (NHANES) 1999-2004, we examined cross-sectional associations between mercury and ANAs (indirect immunofluorescence; cutoff ≥1:80). Three biomarkers of mercury exposure were utilized: hair (available 1999-2000) and total blood (1999-2004) predominantly represented methylmercury, and urinary (1999-2002) inorganic. Survey statistics were used. Multivariable modeling adjusted for several covariates, including age and omega-3 fatty acids.
Results: 16% of females were ANA-positive; 96% of ANA-positives had a nuclear staining pattern of speckled. Mercury geometric means (standard deviations) were: 0.22 (0.03) ppm hair, 0.92 (0.05) µg/L blood, and 0.62 (0.04) µg/L urinary. Hair and blood, but not urinary, mercury were associated with ANA positivity (sample sizes 452, 1352, and 804, respectively), adjusting for confounders: hair odds ratio (OR)=4.10 (95% CI: 1.66, 10.13); blood OR=2.32 (95% CI: 1.07, 5.03) comparing highest versus lowest quantiles. Magnitudes of association were strongest for high-titer (≥1:1280) ANA: hair OR=11.41 (95% CI: 1.60, 81.23); blood OR=5.93 (95% CI: 1.57, 22.47).
Conclusions: Methylmercury, at low levels generally considered safe, was associated with subclinical autoimmunity among reproductive-age females. Autoantibodies may predate clinical disease by years, thus methylmercury exposure may be relevant to future autoimmune disease risk.This work was supported by NIH/NIEHS K01ES019909, NIH/NIEHS
P30ES017885, and NIH/NCRR UL1RR024986. ECS was supported in part by an Arthritis Foundation Health Professional New Investigator Award.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/110512/1/SOMERS_EHP.AdvancePubl 02102015.acco.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/110512/2/Somers_EHP Suppl-1408751.s001.508.pdf114Description of SOMERS_EHP.AdvancePubl 02102015.acco.pdf : Main ArticleDescription of Somers_EHP Suppl-1408751.s001.508.pdf : Supplementary Materia
Structure of a Novel Shoulder-to-Shoulder p24 Dimer in Complex with the Broad-Spectrum Antibody A10F9 and Its Implication in Capsid Assembly
10.1371/journal.pone.0061314PLoS ONE84
Extreme genetic fragility of the HIV-1 capsid
Genetic robustness, or fragility, is defined as the ability, or lack thereof, of a biological entity to maintain function in the face of mutations. Viruses that replicate via RNA intermediates exhibit high mutation rates, and robustness should be particularly advantageous to them. The capsid (CA) domain of the HIV-1 Gag protein is under strong pressure to conserve functional roles in viral assembly, maturation, uncoating, and nuclear import. However, CA is also under strong immunological pressure to diversify. Therefore, it would be particularly advantageous for CA to evolve genetic robustness. To measure the genetic robustness of HIV-1 CA, we generated a library of single amino acid substitution mutants, encompassing almost half the residues in CA. Strikingly, we found HIV-1 CA to be the most genetically fragile protein that has been analyzed using such an approach, with 70% of mutations yielding replication-defective viruses. Although CA participates in several steps in HIV-1 replication, analysis of conditionally (temperature sensitive) and constitutively non-viable mutants revealed that the biological basis for its genetic fragility was primarily the need to coordinate the accurate and efficient assembly of mature virions. All mutations that exist in naturally occurring HIV-1 subtype B populations at a frequency >3%, and were also present in the mutant library, had fitness levels that were >40% of WT. However, a substantial fraction of mutations with high fitness did not occur in natural populations, suggesting another form of selection pressure limiting variation in vivo. Additionally, known protective CTL epitopes occurred preferentially in domains of the HIV-1 CA that were even more genetically fragile than HIV-1 CA as a whole. The extreme genetic fragility of HIV-1 CA may be one reason why cell-mediated immune responses to Gag correlate with better prognosis in HIV-1 infection, and suggests that CA is a good target for therapy and vaccination strategies
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