193 research outputs found
Mosquito Populations from Eastern South Dakota During 2001 and 2002
In 2001, the South Dakota Department of Health initiated a program to monitor mosquitoes in South Dakota for the presence of the West Nile Virus. During the first year (2001), a pilot survey was conducted near Brookings, SD. To collect mosquitoes, CDC miniture light traps were used without carbondioxide baiting, beginning on July 3 and ending on August 2, 2001. Results from this small study (total of 2,042 mosquitoes during 10 collection days) showed that the most common mosquotes were Aedes vexans (88.2%), Culex tarsalis, (5.2%), and Aedes dorsalis (4.9%). An additional survey was conducted during the summer of 2002 focusing on 8 different sites (Brandon, Brookings, Huron, North Sioux City, Oak Lake Field Station, Watertown, Waubay and Yankton) in eastern South Dakota. Mosquitoes were collected with the same traps used for 2001, however, the traps were baited with carbon diaoxide (dry ice). Trapping began on June 1 and ended on September 1, 2002. A total of 18,971 mosquitoes were collected from the 8 sites during the 127 trapping days of this survey. From this population, 21 different mosquito species from 8 different genera were identified. The vast majority of mosquitoes were Aedes vexans (86.3%), but Culex tarsalis was also present in significant numbers (7.2%). Aedes vexans populations varied to a greater degree during the summer than did Culex tarsalis. The public’s perceptions of the danger of West Nile Virus transmission is probably more determined by Aedes population than by Culex populations even though Aedes likely plays little or no role in the transmission of this disease
Fluctuations and differential contraction during regeneration of Hydra vulgaris tissue toroids
We studied regenerating bilayered tissue toroids dissected from Hydra
vulgaris polyps and relate our macroscopic observations to the dynamics of
force-generating mesoscopic cytoskeletal structures. Tissue fragments undergo a
specific toroid-spheroid folding process leading to complete regeneration
towards a new organism. The time scale of folding is too fast for biochemical
signalling or morphogenetic gradients which forced us to assume purely
mechanical self-organization. The initial pattern selection dynamics was
studied by embedding toroids into hydro-gels allowing us to observe the
deformation modes over longer periods of time. We found increasing mechanical
fluctuations which break the toroidal symmetry and discuss the evolution of
their power spectra for various gel stiffnesses. Our observations are related
to single cell studies which explain the mechanical feasibility of the folding
process. In addition, we observed switching of cells from a tissue bound to a
migrating state after folding failure as well as in tissue injury.
We found a supra-cellular actin ring assembled along the toroid's inner edge.
Its contraction can lead to the observed folding dynamics as we could confirm
by finite element simulations. This actin ring in the inner cell layer is
assembled by myosin- driven length fluctuations of supra-cellular
{\alpha}-actin structures (myonemes) in the outer cell-layer.Comment: 19 pages and 8 figures, submitted to New Journal of Physic
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Long-Term Corticosteroid-Sparing Immunosuppression for Cardiac Sarcoidosis.
Background Long-term corticosteroid therapy is the standard of care for treatment of cardiac sarcoidosis (CS). The efficacy of long-term corticosteroid-sparing immunosuppression in CS is unknown. The goal of this study was to assess the efficacy of methotrexate with or without adalimumab for long-term disease suppression in CS, and to assess recurrence and adverse event rates after immunosuppression discontinuation. Methods and Results Retrospective chart review identified treatment-naive CS patients at a single academic medical center who received corticosteroid-sparing maintenance therapy. Demographics, cardiac uptake of 18-fluorodeoxyglucose, and adverse cardiac events were compared before and during treatment and between those with persistent or interrupted immunosuppression. Twenty-eight CS patients were followed for a mean 4.1 (SD 1.5) years. Twenty-five patients received 4 to 8 weeks of high-dose prednisone (>30 mg/day), followed by taper and maintenance therapy with methotrexate±low-dose prednisone (low-dose prednisone, <10 mg/day). Adalimumab was added in 19 patients with persistently active CS or in those with intolerance to methotrexate. Methotrexate±low-dose prednisone resulted in initial reduction (88%) or elimination (60%) of 18-fluorodeoxyglucose uptake, and patients receiving adalimumab-containing regimens experienced improved (84%) or resolved (63%) 18-fluorodeoxyglucose uptake. Radiologic relapse occurred in 8 of 9 patients after immunosuppression cessation, 4 patients on methotrexate-containing regimens, and in no patients on adalimumab-containing regimens. Conclusions Corticosteroid-sparing regimens containing methotrexate with or without adalimumab is an effective maintenance therapy in patients after an initial response is confirmed. Disease recurrence in patients on and off immunosuppression support need for ongoing radiologic surveillance regardless of immunosuppression regimen
Authority Tools for Audiovisual and Music Catalogers: An Annotated List of Useful Resources
The Subcommittee on Authority Tools designed this list to bring together, in one place, descriptions of information sources that are useful when developing authorized headings to support audiovisual and music catalog records. Work began on this project in 1999, and the list was released in 2001. It became a historical OLAC document in 2020. Please note that links in this document were active in 2001 and may no longer exist currently
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Structure of CD20 in complex with the therapeutic monoclonal antibody rituximab.
Cluster of differentiation 20 (CD20) is a B cell membrane protein that is targeted by monoclonal antibodies for the treatment of malignancies and autoimmune disorders but whose structure and function are unknown. Rituximab (RTX) has been in clinical use for two decades, but how it activates complement to kill B cells remains poorly understood. We obtained a structure of CD20 in complex with RTX, revealing CD20 as a compact double-barrel dimer bound by two RTX antigen-binding fragments (Fabs), each of which engages a composite epitope and an extensive homotypic Fab:Fab interface. Our data suggest that RTX cross-links CD20 into circular assemblies and lead to a structural model for complement recruitment. Our results further highlight the potential relevance of homotypic Fab:Fab interactions in targeting oligomeric cell-surface markers
Gradients versus Cycling in Genetic Selection Models
We review the hierarchy of (continuous time) selection models starting with the classical Fisher's viability selection model, and its generalizations when allowing mutations, recombination, sex-dependent viabilities, fertility selection and different mortality rates. We analyse the question in which way Fisher's "Fundamental Theorem of Natural Selection" and Kimura's Maximum Principle can be extended to these more general situations. It turns out that in many cases this is principally impossible since the dynamics becomes cycling or even chaotic
Undifferentiated Connective Tissue Disease-Associated Interstitial Lung Disease: Changes in Lung Function
Undifferentiated connective tissue disease (UCTD) is a distinct clinical entity that may be accompanied by interstitial lung disease (ILD). The natural history of UCTD-ILD is unknown. We hypothesized that patients with UCTD-ILD would be more likely to have improvement in lung function than those with idiopathic pulmonary fibrosis (IPF) during longitudinal follow-up. We identified subjects enrolled in the UCSF ILD cohort study with a diagnosis of IPF or UCTD. The primary outcome compared the presence or absence of a ≥5% increase in percent predicted forced vital capacity (FVC) in IPF and UCTD. Regression models were used to account for potential confounding variables. Ninety subjects were identified; 59 subjects (30 IPF, 29 UCTD) had longitudinal pulmonary function data for inclusion in the analysis. After accounting for baseline pulmonary function tests, treatment, and duration between studies, UCTD was associated with substantial improvement in FVC (odds ratio = 8.23, 95% confidence interval, 1.27–53.2; p = 0.03) during follow-up (median, 8 months) compared with IPF. Patients with UCTD-ILD are more likely to have improved pulmonary function during follow-up than those with IPF. These findings demonstrate the clinical importance of identifying UCTD in patients presenting with an “idiopathic” interstitial pneumonia
Smaller classes promote equitable student participation in STEM
Under embargo until: 2020-07-24As science, technology, engineering, and mathematics (STEM) classrooms in higher education transition from lecturing to active learning, the frequency of student interactions in class increases. Previous research documents a gender bias in participation, with women participating less than would be expected on the basis of their numeric proportions. In the present study, we asked which attributes of the learning environment contribute to decreased female participation: the abundance of in-class interactions, the diversity of interactions, the proportion of women in class, the instructor's gender, the class size, and whether the course targeted lower division (first and second year) or upper division (third or fourth year) students. We calculated likelihood ratios of female participation from over 5300 student–instructor interactions observed across multiple institutions. We falsified several alternative hypotheses and demonstrate that increasing class size has the largest negative effect. We also found that when the instructors used a diverse range of teaching strategies, the women were more likely to participate after small-group discussions.acceptedVersio
Sarcoidosis activates diverse transcriptional programs in bronchoalveolar lavage cells
Abstract
Background
Sarcoidosis is a multisystem immuno-inflammatory disorder of unknown etiology that most commonly involves the lungs. We hypothesized that an unbiased approach to identify pathways activated in bronchoalveolar lavage (BAL) cells can shed light on the pathogenesis of this complex disease.
Methods
We recruited 15 patients with various stages of sarcoidosis and 12 healthy controls. All subjects underwent bronchoscopy with lavage. For each subject, total RNA was extracted from BAL cells and hybridized to an Affymetrix U133A microarray. Rigorous statistical methods were applied to identify differential gene expression between subjects with sarcoidosis vs. controls. To better elucidate pathways differentially activated between these groups, we integrated network and gene set enrichment analyses of BAL cell transcriptional profiles.
Results
Sarcoidosis patients were either non-smokers or former smokers, all had lung involvement and only two were on systemic prednisone. Healthy controls were all non-smokers. Comparison of BAL cell gene expression between sarcoidosis and healthy subjects revealed over 1500 differentially expressed genes. Several previously described immune mediators, such as interferon gamma, were upregulated in the sarcoidosis subjects. Using an integrative computational approach we constructed a modular network of over 80 gene sets that were highly enriched in patients with sarcoidosis. Many of these pathways mapped to inflammatory and immune-related processes including adaptive immunity, T-cell signaling, graft vs. host disease, interleukin 12, 23 and 17 signaling. Additionally, we uncovered a close association between the proteasome machinery and adaptive immunity, highlighting a potentially important and targetable relationship in the pathobiology of sarcoidosis.
Conclusions
BAL cells in sarcoidosis are characterized by enrichment of distinct transcriptional programs involved in immunity and proteasomal processes. Our findings add to the growing evidence implicating alveolar resident immune effector cells in the pathogenesis of sarcoidosis and identify specific pathways whose activation may modulate disease progression
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