MAX 4 and MAX 5 CMB anisotropy measurement constraints on open and flat-Lambda CDM cosmogonies

We account for experimental and observational uncertainties in likelihood analyses of cosmic microwave background (CMB) anisotropy data from the MAX 4 and MAX 5 experiments. These analyses use CMB anisotropy spectra predicted in open and spatially-flat Lambda cold dark matter cosmogonies. Amongst the models considered, the combined MAX data set is most consistent with the CMB anisotropy shape in Omega_0 ~ 0.1-0.2 open models and less so with that in old (t_0 >~ 15 - 16 Gyr, i.e., low h), high baryon density (Omega_B >~ 0.0175/h^2), low density (Omega_0 ~ 0.2 - 0.4), flat-Lambda models. The MAX data alone do not rule out any of the models we consider at the 2-sigma level. Model normalizations deduced from the combined MAX data are consistent with those drawn from the UCSB South Pole 1994 data, except for the flat bandpower model where MAX favours a higher normalization. The combined MAX data normalization for open models with Omega_0 ~ 0.1-0.2 is higher than the upper 2-sigma value of the DMR normalization. The combined MAX data normalization for old (low h), high baryon density, low-density flat-Lambda models is below the lower 2-sigma value of the DMR normalization. Open models with Omega_0 ~ 0.4-0.5 are not far from the shape most favoured by the MAX data, and for these models the MAX and DMR normalizations overlap. The MAX and DMR normalizations also overlap for Omega_0 = 1 and some higher h, lower Omega_B, low-density flat-Lambda models.Comment: Latex, 37 pages, uses aasms4 styl

Using White Dish CMB Anisotropy Data to Probe Open and Flat-Lambda CDM Cosmogonies

We use data from the White Dish experiment to set limits on cosmic microwave background radiation anisotropies in open and spatially-flat-Lambda cold dark matter cosmogonies. We account for the White Dish calibration uncertainty, and marginalize over the offset and gradient removed from the data. Our 2-sigma upper limits are larger than those derived previously. These upper limits are consistent with those derived from the $COBE$-DMR data for all models tested.Comment: 17 pages of latex. Uses aasms4.sty. 4 figures included. Submitted to ApJ

Supernovae Ia Constraints on a Time-Variable Cosmological "Constant"

The energy density of a scalar field $\phi$ with potential $V(\phi) \propto \phi^{-\alpha}$, $\alpha > 0$, behaves like a time-variable cosmological constant that could contribute significantly to the present energy density. Predictions of this spatially-flat model are compared to recent Type Ia supernovae apparent magnitude versus redshift data. A large region of model parameter space is consistent with current observations. (These constraints are based on the exact scalar field model equations of motion, not on the widely used time-independent equation of state fluid approximation equations of motion.) We examine the consequences of also incorporating constraints from recent measurements of the Hubble parameter and the age of the universe in the constant and time-variable cosmological constant models. We also study the effect of using a non-informative prior for the density parameter.Comment: Accepted for publication in Ap

Advancing functional connectivity research from association to causation

Cognition and behavior emerge from brain network interactions, such that investigating causal interactions should be central to the study of brain function. Approaches that characterize statistical associations among neural time series-functional connectivity (FC) methods-are likely a good starting point for estimating brain network interactions. Yet only a subset of FC methods ('effective connectivity') is explicitly designed to infer causal interactions from statistical associations. Here we incorporate best practices from diverse areas of FC research to illustrate how FC methods can be refined to improve inferences about neural mechanisms, with properties of causal neural interactions as a common ontology to facilitate cumulative progress across FC approaches. We further demonstrate how the most common FC measures (correlation and coherence) reduce the set of likely causal models, facilitating causal inferences despite major limitations. Alternative FC measures are suggested to immediately start improving causal inferences beyond these common FC measures

Convertible staircase lift

The present work investigates the design and analysis of a staircase lift, which can be used as a Material Handling System. A staircase lift is a mechanical device for lifting people and wheelchairs up and down the stairs, who may find difficulty in doing so themselves. For sufficiently wide stairs, a rail is mounted to the treads of the stairs. A chair or lifting platform is attached to the rail. A person on the chair or platform is lifted as the chair or platform moves along the rail, old age and goods are to be carried across the staircase. A staircase lift is a type of lift that can be mounted on the staircase without altering civil structure. Not only altering, but the person need not change the seat from the wheelchair to the staircase lift, there is a foldable supporting rod for the staircase lift which directly attaches to the wheelchair. This lift runs on electric power and consists of a motor, reduction gearbox, rope drive, two rails and a sliding chair. In this system, we use a DC motor for changing the polarity of the power supply which will make the motor run in reverse direction. Advantages over the conventional hydraulic lift are no civil structure and alteration is required, low cost, less bulkiness, less power, less maintenance required. Easy design, easy installations can be of industrial use too. Moreover, considering some drawbacks due to weight carrying capacity completely depends upon the capacity of the motor. There is a lot of scope for further modification in the project as using a monorail instead of two, using a belt drive or chain drive instead of a rope drive. Incorporation and automation/timer unit will ease the use of the device. Rack and carrier arrangement for using the device for a curved staircase and use of work & roller reduction gear assembly

Detection of Recent HIV-1 Infection Using a New Limiting-Antigen Avidity Assay: Potential for HIV-1 Incidence Estimates and Avidity Maturation Studies

Background: Accurate and reliable laboratory methods are needed for estimation of HIV-1 incidence to identify the highrisk populations and target and monitor prevention efforts. We previously described a single-well limiting-antigen avidity enzyme immunoassay (LAg-Avidity EIA) to detect recent HIV-1 infection. Methods: We describe here further optimization and characterization of LAg-Avidity EIA, comparing it to the BED assay and a two-well avidity-index (AI) EIA. Specimen sets included longitudinal sera (n = 393), collected from 89 seroconverting individuals from 4 cohorts representing 4 HIV-1 subtypes, and sera from AIDS patients (n = 488) with or without TB coinfections from 3 different cohorts. Ninety seven HIV-1 positive specimens were purchased commercially. The BED assay, LAg-Avidity EIA, AI-EIA and HIV serology were performed, as needed. Results: Monitoring quality control specimens indicated high reproducibility of the LAg-Avidity EIA with coefficient of variation of,10 % in the dynamic range. The LAg-Avidity EIA has an overall mean duration of recency (v) of 141 days (95% CI 119–160) at normalized optical density (ODn) cutoff of 1.0, with similar v in different HIV-1 subtypes and populations (132 to 143 days). Antibody avidity kinetics were similar among individuals and subtypes by both the LAg-Avidity EIA and AI-EIA compared to the HIV-IgG levels measured by the BED assay. The false recent rate among individuals with AIDS was 0.2% with the LAg-Avidity EIA, compared to 2.9 % with the BED assay. Western blot profiles of specimens with increasing avidit

Cryotomography of budding influenza a virus reveals filaments with diverse morphologies that mostly do not bear a genome at their distal end

Influenza viruses exhibit striking variations in particle morphology between strains. Clinical isolates of influenza A virus have been shown to produce long filamentous particles while laboratory-adapted strains are predominantly spherical. However, the role of the filamentous phenotype in the influenza virus infectious cycle remains undetermined. We used cryo-electron tomography to conduct the first three-dimensional study of filamentous virus ultrastructure in particles budding from infected cells. Filaments were often longer than 10 microns and sometimes had bulbous heads at their leading ends, some of which contained tubules we attribute to M1 while none had recognisable ribonucleoprotein (RNP) and hence genome segments. Long filaments that did not have bulbs were infrequently seen to bear an ordered complement of RNPs at their distal ends. Imaging of purified virus also revealed diverse filament morphologies; short rods (bacilliform virions) and longer filaments. Bacilliform virions contained an ordered complement of RNPs while longer filamentous particles were narrower and mostly appeared to lack this feature, but often contained fibrillar material along their entire length. The important ultrastructural differences between these diverse classes of particles raise the possibility of distinct morphogenetic pathways and functions during the infectious process

Non-Acidic Free Fatty Acid Receptor 4 Agonists with Antidiabetic Activity

The free fatty acid receptor 4 (FFA4 or GPR120) has appeared as an interesting potential target for the treatment of metabolic disorders. At present, most FFA4 ligands are carboxylic acids that are assumed to mimic the endogenous long-chain fatty acid agonists. Here, we report preliminary structure-activity relationship studies of a previously disclosed nonacidic sulfonamide FFA4 agonist. Mutagenesis studies indicate that the compounds are orthosteric agonists despite the absence of a carboxylate function. The preferred compounds showed full agonist activity on FFA4 and complete selectivity over FFA1, although a significant fraction of these noncarboxylic acids also showed partial antagonistic activity on FFA1. Studies in normal and diet-induced obese (DIO) mice with the preferred compound 34 showed improved glucose tolerance after oral dosing in an oral glucose tolerance test. Chronic dosing of 34 in DIO mice resulted in significantly increased insulin sensitivity and a moderate but significant reduction in bodyweight, effects that were also present in mice lacking FFA1 but absent in mice lacking FFA4

Mining multi-item drug adverse effect associations in spontaneous reporting systems

<p>Abstract</p> <p>Background</p> <p>Multi-item adverse drug event (ADE) associations are associations relating multiple drugs to possibly multiple adverse events. The current standard in pharmacovigilance is bivariate association analysis, where each single drug-adverse effect combination is studied separately. The importance and difficulty in the detection of multi-item ADE associations was noted in several prominent pharmacovigilance studies. In this paper we examine the application of a well established data mining method known as association rule mining, which we tailored to the above problem, and demonstrate its value. The method was applied to the FDAs spontaneous adverse event reporting system (AERS) with minimal restrictions and expectations on its output, an experiment that has not been previously done on the scale and generality proposed in this work.</p> <p>Results</p> <p>Based on a set of 162,744 reports of suspected ADEs reported to AERS and published in the year 2008, our method identified 1167 multi-item ADE associations. A taxonomy that characterizes the associations was developed based on a representative sample. A significant number (67% of the total) of potential multi-item ADE associations identified were characterized and clinically validated by a domain expert as previously recognized ADE associations. Several potentially novel ADEs were also identified. A smaller proportion (4%) of associations were characterized and validated as known drug-drug interactions.</p> <p>Conclusions</p> <p>Our findings demonstrate that multi-item ADEs are present and can be extracted from the FDA’s adverse effect reporting system using our methodology, suggesting that our method is a valid approach for the initial identification of multi-item ADEs. The study also revealed several limitations and challenges that can be attributed to both the method and quality of data.</p