A comparison of methods for the analysis of binomial clustered outcomes in behavioral research.

PubMed

Ferrari, Alberto; Comelli, Mario

2016-12-01

In behavioral research, data consisting of a per-subject proportion of "successes" and "failures" over a finite number of trials often arise. This clustered binary data are usually non-normally distributed, which can distort inference if the usual general linear model is applied and sample size is small. A number of more advanced methods is available, but they are often technically challenging and a comparative assessment of their performances in behavioral setups has not been performed. We studied the performances of some methods applicable to the analysis of proportions; namely linear regression, Poisson regression, beta-binomial regression and Generalized Linear Mixed Models (GLMMs). We report on a simulation study evaluating power and Type I error rate of these models in hypothetical scenarios met by behavioral researchers; plus, we describe results from the application of these methods on data from real experiments. Our results show that, while GLMMs are powerful instruments for the analysis of clustered binary outcomes, beta-binomial regression can outperform them in a range of scenarios. Linear regression gave results consistent with the nominal level of significance, but was overall less powerful. Poisson regression, instead, mostly led to anticonservative inference. GLMMs and beta-binomial regression are generally more powerful than linear regression; yet linear regression is robust to model misspecification in some conditions, whereas Poisson regression suffers heavily from violations of the assumptions when used to model proportion data. We conclude providing directions to behavioral scientists dealing with clustered binary data and small sample sizes. Copyright © 2016 Elsevier B.V. All rights reserved.

Size-biased distributions in the generalized beta distribution family, with applications to forestry

Treesearch

Mark J. Ducey; Jeffrey H. Gove

2015-01-01

Size-biased distributions arise in many forestry applications, as well as other environmental, econometric, and biomedical sampling problems. We examine the size-biased versions of the generalized beta of the first kind, generalized beta of the second kind and generalized gamma distributions. These distributions include, as special cases, the Dagum (Burr Type III),...

A review and comparison of Bayesian and likelihood-based inferences in beta regression and zero-or-one-inflated beta regression.

PubMed

Liu, Fang; Eugenio, Evercita C

2018-04-01

Beta regression is an increasingly popular statistical technique in medical research for modeling of outcomes that assume values in (0, 1), such as proportions and patient reported outcomes. When outcomes take values in the intervals [0,1), (0,1], or [0,1], zero-or-one-inflated beta (zoib) regression can be used. We provide a thorough review on beta regression and zoib regression in the modeling, inferential, and computational aspects via the likelihood-based and Bayesian approaches. We demonstrate the statistical and practical importance of correctly modeling the inflation at zero/one rather than ad hoc replacing them with values close to zero/one via simulation studies; the latter approach can lead to biased estimates and invalid inferences. We show via simulation studies that the likelihood-based approach is computationally faster in general than MCMC algorithms used in the Bayesian inferences, but runs the risk of non-convergence, large biases, and sensitivity to starting values in the optimization algorithm especially with clustered/correlated data, data with sparse inflation at zero and one, and data that warrant regularization of the likelihood. The disadvantages of the regular likelihood-based approach make the Bayesian approach an attractive alternative in these cases. Software packages and tools for fitting beta and zoib regressions in both the likelihood-based and Bayesian frameworks are also reviewed.

Threading structural model of the manganese-stabilizing protein PsbO reveals presence of two possible beta-sandwich domains.

PubMed

Pazos, F; Heredia, P; Valencia, A; de las Rivas, J

2001-12-01

The manganese-stabilizing protein (PsbO) is an essential component of photosystem II (PSII) and is present in all oxyphotosynthetic organisms. PsbO allows correct water splitting and oxygen evolution by stabilizing the reactions driven by the manganese cluster. Despite its important role, its structure and detailed functional mechanism are still unknown. In this article we propose a structural model based on fold recognition and molecular modeling. This model has additional support from a study of the distribution of characteristics of the PsbO sequence family, such as the distribution of conserved, apolar, tree-determinants, and correlated positions. Our threading results consistently showed PsbO as an all-beta (beta) protein, with two homologous beta domains of approximately 120 amino acids linked by a flexible Proline-Glycine-Glycine (PGG) motif. These features are compatible with a general elongated and flexible architecture, in which the two domains form a sandwich-type structure with Greek key topology. The first domain is predicted to include 8 to 9 beta-strands, the second domain 6 to 7 beta-strands. An Ig-like beta-sandwich structure was selected as a template to build the 3-D model. The second domain has, between the strands, long-loops rich in Pro and Gly that are difficult to model. One of these long loops includes a highly conserved region (between P148 and P174) and a short alpha-helix (between E181 and N188)). These regions are characteristic parts of PsbO and show that the second domain is not so similar to the template. Overall, the model was able to account for much of the experimental data reported by several authors, and it would allow the detection of key residues and regions that are proposed in this article as essential for the structure and function of PsbO. Copyright 2001 Wiley-Liss, Inc.

Relationship between X(5) models and the interacting boson model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Barea, Jose; Departamento de Fisica Atomica, Molecular y Nuclear, Facultad de Fisica, Universidad de Sevilla, Apartado 1065, E-41080 Sevilla; Arias, Jose M.

2010-08-15

The connections between the X(5) models [the original X(5) using an infinite square well, X(5)-{beta}{sup 8}, X(5)-{beta}{sup 6}, X(5)-{beta}{sup 4}, and X(5)-{beta}{sup 2}], based on particular solutions of the geometrical Bohr Hamiltonian with harmonic potential in the {gamma} degree of freedom, and the interacting boson model (IBM) are explored. This work is the natural extension of the work presented in Garcia-Ramos and Arias, Phys. Rev. C 77, 054307 (2008) for the E(5) models. For that purpose, a quite general one- and two-body IBM Hamiltonian is used and a numerical fit to the different X(5) model energies is performed; then themore » obtained wave functions are used to calculate B(E2) transition rates. It is shown that within the IBM one can reproduce well the results for energies and B(E2) transition rates obtained with all these X(5) models, although the agreement is not so impressive as for the E(5) models. From the fitted IBM parameters the corresponding energy surface can be extracted and, surprisingly, only the X(5) case corresponds in the moderately large N limit to an energy surface very close to the one expected for a critical point, whereas the rest of models are situated a little further away.« less

Observation and Interpretation of Lunar Occultations. Ph.D. Thesis; [Uranus and beta Capricorni

NASA Technical Reports Server (NTRS)

Radick, R. R.

1978-01-01

The importance of timings and high resolution astrometry in occultation observations is discussed as well as the occultation process itself. The design and operation of the telescope, photodetector, and data acquisition systems are described. Methods are presented for data analysis and model fitting. Observations of beta Capricorni and Uranus occultations are examined. General conclusions concerning occultation observations are explored and future activities at Prairie Observatory are discussed.

Guidelines for Use of the Approximate Beta-Poisson Dose-Response Model.

PubMed

Xie, Gang; Roiko, Anne; Stratton, Helen; Lemckert, Charles; Dunn, Peter K; Mengersen, Kerrie

2017-07-01

For dose-response analysis in quantitative microbial risk assessment (QMRA), the exact beta-Poisson model is a two-parameter mechanistic dose-response model with parameters α>0 and β>0, which involves the Kummer confluent hypergeometric function. Evaluation of a hypergeometric function is a computational challenge. Denoting PI(d) as the probability of infection at a given mean dose d, the widely used dose-response model PI(d)=1-(1+dβ)-α is an approximate formula for the exact beta-Poisson model. Notwithstanding the required conditions α<β and β>1, issues related to the validity and approximation accuracy of this approximate formula have remained largely ignored in practice, partly because these conditions are too general to provide clear guidance. Consequently, this study proposes a probability measure Pr(0 < r < 1 | α̂, β̂) as a validity measure (r is a random variable that follows a gamma distribution; α̂ and β̂ are the maximum likelihood estimates of α and β in the approximate model); and the constraint conditions β̂>(22α̂)0.50 for 0.02<α̂<2 as a rule of thumb to ensure an accurate approximation (e.g., Pr(0 < r < 1 | α̂, β̂) >0.99) . This validity measure and rule of thumb were validated by application to all the completed beta-Poisson models (related to 85 data sets) from the QMRA community portal (QMRA Wiki). The results showed that the higher the probability Pr(0 < r < 1 | α̂, β̂), the better the approximation. The results further showed that, among the total 85 models examined, 68 models were identified as valid approximate model applications, which all had a near perfect match to the corresponding exact beta-Poisson model dose-response curve. © 2016 Society for Risk Analysis.

Finite Group Invariance and Solution of Jaynes-Cummings Hamiltonian

DOE Office of Scientific and Technical Information (OSTI.GOV)

Haydargil, Derya; Koc, Ramazan

2004-10-04

The finite group invariance of the E x {beta} and Jaynes-Cummings models are studied. A method is presented to obtain finite group invariance of the E x {beta} system.A suitable transformation of a Jaynes-Cummings Hamiltonian leads to equivalence of E x {beta} system. Then a general method is applied to obtain the solution of Jaynes-Cummings Hamiltonian with Kerr nonlinearity. Number operator for this structure and the generators of su(2) algebra are used to find the eigenvalues of the Jaynes-Cummings Hamiltonian for different states. By using the invariance of number operator the solution of modified Jaynes-Cummings Hamiltonian is also discussed.

Hierarchical dose response of E. coli O157:H7 from human outbreaks incorporating heterogeneity in exposure.

PubMed

Teunis, P F M; Ogden, I D; Strachan, N J C

2008-06-01

The infectivity of pathogenic microorganisms is a key factor in the transmission of an infectious disease in a susceptible population. Microbial infectivity is generally estimated from dose-response studies in human volunteers. This can only be done with mildly pathogenic organisms. Here a hierarchical Beta-Poisson dose-response model is developed utilizing data from human outbreaks. On the lowest level each outbreak is modelled separately and these are then combined at a second level to produce a group dose-response relation. The distribution of foodborne pathogens often shows strong heterogeneity and this is incorporated by introducing an additional parameter to the dose-response model, accounting for the degree of overdispersion relative to Poisson distribution. It was found that heterogeneity considerably influences the shape of the dose-response relationship and increases uncertainty in predicted risk. This uncertainty is greater than previously reported surrogate and outbreak models using a single level of analysis. Monte Carlo parameter samples (alpha, beta of the Beta-Poisson model) can be readily incorporated in risk assessment models built using tools such as S-plus and @ Risk.

General Nonlinear Ferroelectric Model v. Beta

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dong, Wen; Robbins, Josh

2017-03-14

The purpose of this software is to function as a generalized ferroelectric material model. The material model is designed to work with existing finite element packages by providing updated information on material properties that are nonlinear and dependent on loading history. The two major nonlinear phenomena this model captures are domain-switching and phase transformation. The software itself does not contain potentially sensitive material information and instead provides a framework for different physical phenomena observed within ferroelectric materials. The model is calibrated to a specific ferroelectric material through input parameters provided by the user.

THE SPATIO-TEMPORAL EVOLUTION OF SOLAR FLARES OBSERVED WITH AIA/SDO: FRACTAL DIFFUSION, SUB-DIFFUSION, OR LOGISTIC GROWTH?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aschwanden, Markus J., E-mail: aschwanden@lmsal.com

2012-09-20

We explore the spatio-temporal evolution of solar flares by fitting a radial expansion model r(t) that consists of an exponentially growing acceleration phase, followed by a deceleration phase that is parameterized by the generalized diffusion function r(t){proportional_to}{kappa}(t - t{sub 1}){sup {beta}/2}, which includes the logistic growth limit ({beta} = 0), sub-diffusion ({beta} = 0-1), classical diffusion ({beta} = 1), super-diffusion ({beta} = 1-2), and the linear expansion limit ({beta} = 2). We analyze all M- and X-class flares observed with Geostationary Operational Environmental Satellite and Atmospheric Imaging Assembly/Solar Dynamics Observatory (SDO) during the first two years of the SDO mission,more » amounting to 155 events. We find that most flares operate in the sub-diffusive regime ({beta} = 0.53 {+-} 0.27), which we interpret in terms of anisotropic chain reactions of intermittent magnetic reconnection episodes in a low plasma-{beta} corona. We find a mean propagation speed of v = 15 {+-} 12 km s{sup -1}, with maximum speeds of v{sub max} = 80 {+-} 85 km s{sup -1} per flare, which is substantially slower than the sonic speeds expected for thermal diffusion of flare plasmas. The diffusive characteristics established here (for the first time for solar flares) is consistent with the fractal-diffusive self-organized criticality model, which predicted diffusive transport merely based on cellular automaton simulations.« less

Trending in Probability of Collision Measurements via a Bayesian Zero-Inflated Beta Mixed Model

NASA Technical Reports Server (NTRS)

Vallejo, Jonathon; Hejduk, Matt; Stamey, James

2015-01-01

We investigate the performance of a generalized linear mixed model in predicting the Probabilities of Collision (Pc) for conjunction events. Specifically, we apply this model to the log(sub 10) transformation of these probabilities and argue that this transformation yields values that can be considered bounded in practice. Additionally, this bounded random variable, after scaling, is zero-inflated. Consequently, we model these values using the zero-inflated Beta distribution, and utilize the Bayesian paradigm and the mixed model framework to borrow information from past and current events. This provides a natural way to model the data and provides a basis for answering questions of interest, such as what is the likelihood of observing a probability of collision equal to the effective value of zero on a subsequent observation.

Role of general and specific competence skills in protecting inner-city adolescents from alcohol use.

PubMed

Epstein, J A; Griffin, K W; Botvin, G J

2000-05-01

The purpose of this longitudinal investigation was to test whether higher levels of general competence are linked to greater refusal assertiveness that is, in turn, related to less subsequent alcohol use among inner-city adolescents. A large sample of students attending 22 middle and junior high schools in New York City participated. Students completed surveys at baseline, at 1-year follow-up and at 2-year follow-up (N = 1,459; 54% female). The students self-reported alcohol use. decision-making skills, self-efficacy and refusal assertiveness. Teams of three to five data collectors administered the questionnaire following a standardized protocol. The data were collected in school during a regular 40-minute class period. According to the tested structural equation model, Decision Making (beta = .07, p < .05) and Self-Efficacy (beta = .24, p < .001) predicted higher Refusal Assertiveness and this greater assertiveness predicted less drinking at the 2-year follow-up (beta = -.21, p < .001). Earlier drinking predicted 2-year follow-up drinking (beta = .40, p < .001). Goodness-of-fit indices were excellent (chi2 = 1107.9, 238 df, N = 1,438, p < .001; NFI = .93, NNFI = .94, CFI = .95). The tested model had a good fit and was parsimonious and consistent with theory. This research highlights the importance of addressing decision-making skills, self-efficacy and refusal assertiveness within adolescent alcohol prevention programs.

The current contribution of molecular factors to risk estimation in neuroblastoma patients.

PubMed

Berthold, F; Sahin, K; Hero, B; Christiansen, H; Gehring, M; Harms, D; Horz, S; Lampert, F; Schwab, M; Terpe, J

1997-10-01

The association of molecular characteristics with prognosis has been reported, but not their relationship with each other and their impact in the context of known clinical risk factors. In this study, data of 1249 consecutive intent-to-treat-neuroblastoma patients with more than 1 year follow-up were examined by multivariate analysis using loglinear and Cox proportional hazard regression models on a stage-related basis (stages 1-3: 600, 4S: 116, 4: 533). In a first step, risk factors were identified from 18 selected clinical variables, and risk groups defined. The second step investigated whether molecular characteristics (MYCN, LOH 1p, del 1p, CD44, N-ras, NGF-R, bcl-2, APO-1 (CD95)) contributed additional prognostic information to the model. The loglinear model demonstrated several interactions between clinical factors. By the Cox regression model, seven independent clinical risk factors were found for stages 1-3, seven for stage 4 and two for stage 4S. By subsequent introduction of all molecular variables, MYCN amplification only added significant prognostic information to the clinical factors in localised and stage 4 neuroblastoma. The models allowed the definition of risk groups for stages 1-3 patients by age (e beta = 5.09) and MYCN (e beta = 4.26), for stage 4 by MYCN (e beta = 2.78) and number of symptoms (e beta = 2.44) and for stage 4S by platelet count (e beta = 3.91) and general condition (e beta = 2.99). Molecular factors and in particular MYCN contribute significantly to risk estimation. In conjunction with clinical factors, they are powerful tools to define risk groups in neuroblastoma.

On the mathematical analysis of Ebola hemorrhagic fever: deathly infection disease in West African countries.

PubMed

Atangana, Abdon; Goufo, Emile Franc Doungmo

2014-01-01

For a given West African country, we constructed a model describing the spread of the deathly disease called Ebola hemorrhagic fever. The model was first constructed using the classical derivative and then converted to the generalized version using the beta-derivative. We studied in detail the endemic equilibrium points and provided the Eigen values associated using the Jacobian method. We furthered our investigation by solving the model numerically using an iteration method. The simulations were done in terms of time and beta. The study showed that, for small portion of infected individuals, the whole country could die out in a very short period of time in case there is not good prevention.

Bioaccumulation and Aquatic System Simulator (BASS) User's Manual Beta Test Version 2.1. EPA/600/R-01/035

EPA Pesticide Factsheets

this report describes the theoretical development, parameterization, and application software of a generalized, community-based, bioaccumulation model called BASS (Bioaccumulation and Aquatic System Simulator).

A powerful and flexible approach to the analysis of RNA sequence count data.

PubMed

Zhou, Yi-Hui; Xia, Kai; Wright, Fred A

2011-10-01

A number of penalization and shrinkage approaches have been proposed for the analysis of microarray gene expression data. Similar techniques are now routinely applied to RNA sequence transcriptional count data, although the value of such shrinkage has not been conclusively established. If penalization is desired, the explicit modeling of mean-variance relationships provides a flexible testing regimen that 'borrows' information across genes, while easily incorporating design effects and additional covariates. We describe BBSeq, which incorporates two approaches: (i) a simple beta-binomial generalized linear model, which has not been extensively tested for RNA-Seq data and (ii) an extension of an expression mean-variance modeling approach to RNA-Seq data, involving modeling of the overdispersion as a function of the mean. Our approaches are flexible, allowing for general handling of discrete experimental factors and continuous covariates. We report comparisons with other alternate methods to handle RNA-Seq data. Although penalized methods have advantages for very small sample sizes, the beta-binomial generalized linear model, combined with simple outlier detection and testing approaches, appears to have favorable characteristics in power and flexibility. An R package containing examples and sample datasets is available at http://www.bios.unc.edu/research/genomic_software/BBSeq yzhou@bios.unc.edu; fwright@bios.unc.edu Supplementary data are available at Bioinformatics online.

Beta-glucosidase I variants with improved properties

DOEpatents

Bott, Richard R.; Kaper, Thijs; Kelemen, Bradley; Goedegebuur, Frits; Hommes, Ronaldus Wilhelmus; Kralj, Slavko; Kruithof, Paulien; Nikolaev, Igor; Van Der Kley, Wilhelmus Antonious Hendricus; Van Lieshout, Johannes Franciscus Thomas; Van Stigt Thans, Sander

2016-09-20

The present disclosure is generally directed to enzymes and in particular beta-glucosidase variants. Also described are nucleic acids encoding beta-glucosidase variants, compositions comprising beta-glucosidase variants, methods of using beta-glucosidase variants, and methods of identifying additional useful beta-glucosidase variants.

Temporally variable environments maintain more beta-diversity in Mediterranean landscapes

NASA Astrophysics Data System (ADS)

Martin, Beatriz; Ferrer, Miguel

2015-10-01

We examined the relationships between different environmental factors and the alpha and beta-diversity of terrestrial vertebrates (birds, mammals, amphibians and reptiles) in a Mediterranean region at the landscape level. We investigated whether the mechanisms underlying alpha and beta-diversity patterns are influenced by energy availability, habitat heterogeneity and temporal variability and if the drivers of the diversity patterns differed between both components of diversity. We defined alpha-diversity as synonym of species richness whereas beta-diversity was measured as distinctiveness. We evaluated a total of 13 different predictors using generalized linear mixed model (GLMM) analysis. Habitat spatial heterogeneity increased alpha-diversity, but contrastingly, it did not significantly affect beta-diversity among sites. Disturbed landscapes may show higher habitat spatial variation and higher alpha-diversity due to the contribution of highly generalist species that are wide-distributed and do not differ in composition (beta-diversity) among different sites within the region. Contrastingly, higher beta-diversity levels were negatively related to more stable sites in terms of temporal environmental variation. This negative relationship between environmental stability and beta-diversity levels is explained in terms of species adaptation to the local environmental conditions. Our study highlights the importance of temporal environmental variability in maintaining beta-diversity patterns under highly variable environmental conditions.

Biodiversity and ecosystem stability across scales in metacommunities

PubMed Central

Wang, Shaopeng; Loreau, Michel

2016-01-01

Although diversity-stability relationships have been extensively studied in local ecosystems, the global biodiversity crisis calls for an improved understanding of these relationships in a spatial context. Here we use a dynamical model of competitive metacommunities to study the relationships between species diversity and ecosystem variability across scales. We derive analytic relationships under a limiting case; these results are extended to more general cases with numerical simulations. Our model shows that, while alpha diversity decreases local ecosystem variability, beta diversity generally contributes to increasing spatial asynchrony among local ecosystems. Consequently, both alpha and beta diversity provide stabilizing effects for regional ecosystems, through local and spatial insurance effects, respectively. We further show that at the regional scale, the stabilizing effect of biodiversity increases as spatial environmental correlation increases. Our findings have important implications for understanding the interactive effects of global environmental changes (e.g. environmental homogenization) and biodiversity loss on ecosystem sustainability at large scales. PMID:26918536

Mechanism of Resilin Elasticity

PubMed Central

Qin, Guokui; Hu, Xiao; Cebe, Peggy; Kaplan, David L.

2012-01-01

Resilin is critical in the flight and jumping systems of insects as a polymeric rubber-like protein with outstanding elasticity. However, insight into the underlying molecular mechanisms responsible for resilin elasticity remains undefined. Here we report the structure and function of resilin from Drosophila CG15920. A reversible beta-turn transition was identified in the peptide encoded by exon III and for full length resilin during energy input and release, features that correlate to the rapid deformation of resilin during functions in vivo. Micellar structures and nano-porous patterns formed after beta-turn structures were present via changes in either the thermal or mechanical inputs. A model is proposed to explain the super elasticity and energy conversion mechanisms of resilin, providing important insight into structure-function relationships for this protein. Further, this model offers a view of elastomeric proteins in general where beta-turn related structures serve as fundamental units of the structure and elasticity. PMID:22893127

High frequency fishbone driven by passing energetic ions in tokamak plasmas

DOE PAGES

Wang, Feng; Yu, L. M.; Fu, G. Y.; ...

2017-03-22

High frequency fishbone instability driven by passing energetic ions was first reported in the Princeton beta experiment with tangential neutral-beam-injection (Heidbrink et al 1986 Phys. Rev. Lett. 57 835–8). It could play an important role for ITER-like burning plasmas, where α particles are mostly passing particles. In this work, a generalized energetic ion distribution function and finite drift orbit width effect are considered to improve the theoretical model for passing particle driving fishbone instability. For purely passing energetic ions with zero drift orbit width, the kinetic energymore » $$\\delta {{W}_{k}}$$ is derived analytically. The derived analytic expression is more accurate as compared to the result of previous work. For a generalized energetic ion distribution function, the fishbone dispersion relation is derived and is solved numerically. As a result, numerical results show that broad and off-axis beam density profiles can significantly increase the beam ion beta threshold $${{\\beta}_{c}}$$ for instability and decrease mode frequency.« less

A Generalized Form of Context-Dependent Psychophysiological Interactions (gPPI): A Comparison to Standard Approaches

PubMed Central

McLaren, Donald G.; Ries, Michele L.; Xu, Guofan; Johnson, Sterling C.

2012-01-01

Functional MRI (fMRI) allows one to study task-related regional responses and task-dependent connectivity analysis using psychophysiological interaction (PPI) methods. The latter affords the additional opportunity to understand how brain regions interact in a task-dependent manner. The current implementation of PPI in Statistical Parametric Mapping (SPM8) is configured primarily to assess connectivity differences between two task conditions, when in practice fMRI tasks frequently employ more than two conditions. Here we evaluate how a generalized form of context-dependent PPI (gPPI; http://www.nitrc.org/projects/gppi), which is configured to automatically accommodate more than two task conditions in the same PPI model by spanning the entire experimental space, compares to the standard implementation in SPM8. These comparisons are made using both simulations and an empirical dataset. In the simulated dataset, we compare the interaction beta estimates to their expected values and model fit using the Akaike Information Criterion (AIC). We found that interaction beta estimates in gPPI were robust to different simulated data models, were not different from the expected beta value, and had better model fits than when using standard PPI (sPPI) methods. In the empirical dataset, we compare the model fit of the gPPI approach to sPPI. We found that the gPPI approach improved model fit compared to sPPI. There were several regions that became non-significant with gPPI. These regions all showed significantly better model fits with gPPI. Also, there were several regions where task-dependent connectivity was only detected using gPPI methods, also with improved model fit. Regions that were detected with all methods had more similar model fits. These results suggest that gPPI may have greater sensitivity and specificity than standard implementation in SPM. This notion is tempered slightly as there is no gold standard; however, data simulations with a known outcome support our conclusions about gPPI. In sum, the generalized form of context-dependent PPI approach has increased flexibility of statistical modeling, and potentially improves model fit, specificity to true negative findings, and sensitivity to true positive findings. PMID:22484411

DOE Office of Scientific and Technical Information (OSTI.GOV)

Connor, D.M.; Miller, L.; Benveniste, H.

Our understanding of early development in Alzheimer's disease (AD) is clouded by the scale at which the disease progresses; amyloid beta (A{beta}) plaques, a hallmark feature of AD, are small ({approx} 50 {micro}m) and low contrast in diagnostic clinical imaging techniques. Diffraction enhanced imaging (DEI), a phase contrast x-ray imaging technique, has greater soft tissue contrast than conventional radiography and generates higher resolution images than magnetic resonance microimaging. Thus, in this proof of principle study, DEI in micro-CT mode was performed on the brains of AD-model mice to determine if DEI can visualize A{beta} plaques. Results revealed small nodules inmore » the cortex and hippocampus of the brain. Histology confirmed that the features seen in the DEI images of the brain were A{beta} plaques. Several anatomical structures, including hippocampal subregions and white matter tracks, were also observed. Thus, DEI has strong promise in early diagnosis of AD, as well as general studies of the mouse brain.« less

A Bayesian beta distribution model for estimating rainfall IDF curves in a changing climate

NASA Astrophysics Data System (ADS)

Lima, Carlos H. R.; Kwon, Hyun-Han; Kim, Jin-Young

2016-09-01

The estimation of intensity-duration-frequency (IDF) curves for rainfall data comprises a classical task in hydrology studies to support a variety of water resources projects, including urban drainage and the design of flood control structures. In a changing climate, however, traditional approaches based on historical records of rainfall and on the stationary assumption can be inadequate and lead to poor estimates of rainfall intensity quantiles. Climate change scenarios built on General Circulation Models offer a way to access and estimate future changes in spatial and temporal rainfall patterns at the daily scale at the utmost, which is not as fine temporal resolution as required (e.g. hours) to directly estimate IDF curves. In this paper we propose a novel methodology based on a four-parameter beta distribution to estimate IDF curves conditioned on the observed (or simulated) daily rainfall, which becomes the time-varying upper bound of the updated nonstationary beta distribution. The inference is conducted in a Bayesian framework that provides a better way to take into account the uncertainty in the model parameters when building the IDF curves. The proposed model is tested using rainfall data from four stations located in South Korea and projected climate change Representative Concentration Pathways (RCPs) scenarios 6 and 8.5 from the Met Office Hadley Centre HadGEM3-RA model. The results show that the developed model fits the historical data as good as the traditional Generalized Extreme Value (GEV) distribution but is able to produce future IDF curves that significantly differ from the historically based IDF curves. The proposed model predicts for the stations and RCPs scenarios analysed in this work an increase in the intensity of extreme rainfalls of short duration with long return periods.

Stigma as a barrier to recognizing personal mental illness and seeking help: a prospective study among untreated persons with mental illness.

PubMed

Schomerus, Georg; Stolzenburg, Susanne; Freitag, Simone; Speerforck, Sven; Janowitz, Deborah; Evans-Lacko, Sara; Muehlan, Holger; Schmidt, Silke

2018-04-20

It is unclear to what extent failure to recognize symptoms as potential sign of a mental illness is impeding service use, and how stigmatizing attitudes interfere with this process. In a prospective study, we followed a community sample of 188 currently untreated persons with mental illness (predominantly depression) over 6 months. We examined how lack of knowledge, prejudice and discrimination impacted on self-identification as having a mental illness, perceived need, intention to seek help, and help-seeking, both with respect to primary care (visiting a general practitioner, GP) and specialist care (seeing a mental health professional, MHP). 67% sought professional help within 6 months. Fully saturated path models accounting for baseline depressive symptoms, previous treatment experience, age and gender showed that self-identification predicted need (beta 0.32, p < 0.001), and need predicted intention (GP: beta 0.45, p < 0.001; MHP: beta 0.38, p < 0.001). Intention predicted service use with a MHP after 6 months (beta 0.31, p < 0.01; GP: beta 0.17, p = 0.093). More knowledge was associated with more self-identification (beta 0.21, p < 0.01), while support for discrimination was associated with lower self-identification (beta - 0.14, p < 0.05). Blaming persons with mental illness for their problem was associated with lower perceived need (beta - 0.16, p < 0.05). Our models explained 37% of the variance of seeking help with a MHP, and 33% of help-seeking with a GP. Recognizing one's own mental illness and perceiving a need for help are impaired by lack of knowledge, prejudice, and discrimination. Self-identification is a relevant first step when seeking help for mental disorders.

Gay-Berne and electrostatic multipole based coarse-grain potential in implicit solvent

NASA Astrophysics Data System (ADS)

Wu, Johnny; Zhen, Xia; Shen, Hujun; Li, Guohui; Ren, Pengyu

2011-10-01

A general, transferable coarse-grain (CG) framework based on the Gay-Berne potential and electrostatic point multipole expansion is presented for polypeptide simulations. The solvent effect is described by the Generalized Kirkwood theory. The CG model is calibrated using the results of all-atom simulations of model compounds in solution. Instead of matching the overall effective forces produced by atomic models, the fundamental intermolecular forces such as electrostatic, repulsion-dispersion, and solvation are represented explicitly at a CG level. We demonstrate that the CG alanine dipeptide model is able to reproduce quantitatively the conformational energy of all-atom force fields in both gas and solution phases, including the electrostatic and solvation components. Replica exchange molecular dynamics and microsecond dynamic simulations of polyalanine of 5 and 12 residues reveal that the CG polyalanines fold into "alpha helix" and "beta sheet" structures. The 5-residue polyalanine displays a substantial increase in the "beta strand" fraction relative to the 12-residue polyalanine. The detailed conformational distribution is compared with those reported from recent all-atom simulations and experiments. The results suggest that the new coarse-graining approach presented in this study has the potential to offer both accuracy and efficiency for biomolecular modeling.

A powerful and flexible approach to the analysis of RNA sequence count data

PubMed Central

Zhou, Yi-Hui; Xia, Kai; Wright, Fred A.

2011-01-01

Motivation: A number of penalization and shrinkage approaches have been proposed for the analysis of microarray gene expression data. Similar techniques are now routinely applied to RNA sequence transcriptional count data, although the value of such shrinkage has not been conclusively established. If penalization is desired, the explicit modeling of mean–variance relationships provides a flexible testing regimen that ‘borrows’ information across genes, while easily incorporating design effects and additional covariates. Results: We describe BBSeq, which incorporates two approaches: (i) a simple beta-binomial generalized linear model, which has not been extensively tested for RNA-Seq data and (ii) an extension of an expression mean–variance modeling approach to RNA-Seq data, involving modeling of the overdispersion as a function of the mean. Our approaches are flexible, allowing for general handling of discrete experimental factors and continuous covariates. We report comparisons with other alternate methods to handle RNA-Seq data. Although penalized methods have advantages for very small sample sizes, the beta-binomial generalized linear model, combined with simple outlier detection and testing approaches, appears to have favorable characteristics in power and flexibility. Availability: An R package containing examples and sample datasets is available at http://www.bios.unc.edu/research/genomic_software/BBSeq Contact: yzhou@bios.unc.edu; fwright@bios.unc.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:21810900

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gaponov, Yu. V.

A special Majorana model for three neutrino flavors is developed on the basis of the Pauli transformation group. In this model, the neutrinos possess a partially conserved generalized lepton (Pauli) charge that makes it possible to discriminate between neutrinos of different type. It is shown that, within the model in question, a transition from the basic 'mass' representation, where the average value of this charge is zero, to the representation associated with physical neutrinos characterized by specific Pauli 'flavor' charges establishes a relation between the neutrino mixing angles {theta}{sub mix,12}, {theta}{sub mix,23}, and {theta}{sub mix,13} and an additional relation betweenmore » the Majorana neutrino masses. The Lagrangian mass part, which includes a term invariant under Pauli transformations and a representation-dependent term, concurrently assumes a 'quasi-Dirac' form. With allowance for these relations, the existing set of experimental data on the features of neutrino oscillations makes it possible to obtain quantitative estimates for the absolute values of the neutrino masses and the 2{beta}-decay mass parameter m{sub {beta}{beta}} and a number of additional constraints on the neutrino mixing angles.« less

Putative signaling action of amelogenin utilizes the Wnt/beta-catenin pathway.

PubMed

Matsuzawa, M; Sheu, T-J; Lee, Y-J; Chen, M; Li, T-F; Huang, C T; Holz, J D; Puzas, J E

2009-06-01

While it has long been known that amelogenin is essential for the proper development of enamel, its role has generally been seen as structural in nature. However, our new data implicate this protein in the regulation of cell signaling pathways in periodontal ligament cells and osteoblasts. In this article we report the successful purification of a recombinant mouse amelogenin protein and demonstrate that it has signaling activity in isolated mouse calvarial cells and human periodontal ligament cells. To determine the regulatory function of canonical Wnt signaling by amelogenin, we used TOPGAL transgenic mice. These mice express a beta-galactosidase transgene under the control of a LEF/TCF and beta-catenin-inducible promoter. To investigate in greater detail the molecular mechanisms involved in the beta-catenin signaling pathway, isolated osteoblasts and periodontal ligament cells were exposed to full-length recombinant mouse amelogenin and were evaluated for phenotypic changes and beta-catenin signaling using a TOPFLASH construct and the LacZ reporter gene. In these in vitro models, we showed that amelogenin can activate beta-catenin signaling. Using the TOPGAL transgenic mouse we showed that amelogenin expression in vivo is localized mainly around the root, the periodontal ligament and the alveolar bone.

Estimating riparian understory vegetation cover with beta regression and copula models

USGS Publications Warehouse

Eskelson, Bianca N.I.; Madsen, Lisa; Hagar, Joan C.; Temesgen, Hailemariam

2011-01-01

Understory vegetation communities are critical components of forest ecosystems. As a result, the importance of modeling understory vegetation characteristics in forested landscapes has become more apparent. Abundance measures such as shrub cover are bounded between 0 and 1, exhibit heteroscedastic error variance, and are often subject to spatial dependence. These distributional features tend to be ignored when shrub cover data are analyzed. The beta distribution has been used successfully to describe the frequency distribution of vegetation cover. Beta regression models ignoring spatial dependence (BR) and accounting for spatial dependence (BRdep) were used to estimate percent shrub cover as a function of topographic conditions and overstory vegetation structure in riparian zones in western Oregon. The BR models showed poor explanatory power (pseudo-R2 ≤ 0.34) but outperformed ordinary least-squares (OLS) and generalized least-squares (GLS) regression models with logit-transformed response in terms of mean square prediction error and absolute bias. We introduce a copula (COP) model that is based on the beta distribution and accounts for spatial dependence. A simulation study was designed to illustrate the effects of incorrectly assuming normality, equal variance, and spatial independence. It showed that BR, BRdep, and COP models provide unbiased parameter estimates, whereas OLS and GLS models result in slightly biased estimates for two of the three parameters. On the basis of the simulation study, 93–97% of the GLS, BRdep, and COP confidence intervals covered the true parameters, whereas OLS and BR only resulted in 84–88% coverage, which demonstrated the superiority of GLS, BRdep, and COP over OLS and BR models in providing standard errors for the parameter estimates in the presence of spatial dependence.

Physicians' shared decision-making behaviors in depression care.

PubMed

Young, Henry N; Bell, Robert A; Epstein, Ronald M; Feldman, Mitchell D; Kravitz, Richard L

2008-07-14

Although shared decision making (SDM) has been reported to facilitate quality care, few studies have explored the extent to which SDM is implemented in primary care and factors that influence its application. This study assesses the extent to which physicians enact SDM behaviors and describes factors associated with physicians' SDM behaviors within the context of depression care. In a secondary analysis of data from a randomized experiment, we coded 287 audiorecorded interactions between physicians and standardized patients (SPs) using the Observing Patient Involvement (OPTION) system to assess physician SDM behaviors. We performed a series of generalized linear mixed model analyses to examine physician and patient characteristics associated with SDM behavior. The mean (SD) OPTION score was 11.4 (3.3) of 48 possible points. Older physicians (partial correlation coefficient = -0.29; beta = -0.09; P < .01) and physicians who practiced in a health maintenance organization setting (beta = -1.60; P < .01) performed fewer SDM behaviors. Longer visit duration was associated with more SDM behaviors (partial correlation coefficient = 0.31; beta = 0.08; P < .01). In addition, physicians enacted more SDM behaviors with SPs who made general (beta = 2.46; P < .01) and brand-specific (beta = 2.21; P < .01) medication requests compared with those who made no request. In the context of new visits for depressive symptoms, primary care physicians performed few SDM behaviors. However, physician SDM behaviors are influenced by practice setting and patient-initiated requests for medication. Additional research is needed to identify interventions that encourage SDM when indicated.

Biodiversity and ecosystem stability across scales in metacommunities.

PubMed

Wang, Shaopeng; Loreau, Michel

2016-05-01

Although diversity-stability relationships have been extensively studied in local ecosystems, the global biodiversity crisis calls for an improved understanding of these relationships in a spatial context. Here, we use a dynamical model of competitive metacommunities to study the relationships between species diversity and ecosystem variability across scales. We derive analytic relationships under a limiting case; these results are extended to more general cases with numerical simulations. Our model shows that, while alpha diversity decreases local ecosystem variability, beta diversity generally contributes to increasing spatial asynchrony among local ecosystems. Consequently, both alpha and beta diversity provide stabilising effects for regional ecosystems, through local and spatial insurance effects respectively. We further show that at the regional scale, the stabilising effect of biodiversity increases as spatial environmental correlation increases. Our findings have important implications for understanding the interactive effects of global environmental changes (e.g. environmental homogenisation) and biodiversity loss on ecosystem sustainability at large scales. © 2016 John Wiley & Sons Ltd/CNRS.

Side effects of beta-blocker treatments as related to the central nervous system.

PubMed

Dahlöf, C; Dimenäs, E

1990-04-01

During the last decade beta-adrenoceptor antagonists have become one of the first-line treatments for hypertension. Generally, they have been shown to be safe with a low frequency of serious side effects. However, minor subjective symptoms, usually considered to be CNS-related, have been reported for all beta-blockers used. Thus, all beta-blockers on the market seem to have a high benefit:risk ratio; independent of their physicochemical properties and pharmacodynamic profile, however, they seem to cause CNS-related side effects to about the same extent. These minor side effects, the mechanisms of which are unclear, consist of subtle effects on general well being, decreased initiative, a depressed frame of mind, and disturbed sleep. Generally, however, beta-blockers in therapeutic dosages do not affect the qualitative functions of the brain. The results so far available have been obtained primarily by using objective methods. Further comparison has now been initiated using documented subjective methods to investigate whether the objectively documented differences are of any clinical relevance to the patient's quality of life. Although it cannot be claimed with certainty, nonselective beta-blockers seem to cause CNS-related side effects to a greater extent than beta 1-selective blockers. Differences in the degree of hydrophilicity of the beta-blocker are apparently of no clinical relevance in this respect. Rather, the plasma concentration of the beta-blocking drug (degree of beta-blockade) seems to be the major determinant of whether or not CNS-related symptoms appear in susceptible patients.

Interactions of beta-blockers with model lipid membranes: molecular view of the interaction of acebutolol, oxprenolol, and propranolol with phosphatidylcholine vesicles by time-dependent fluorescence shift and molecular dynamics simulations.

PubMed

Först, Gesche; Cwiklik, Lukasz; Jurkiewicz, Piotr; Schubert, Rolf; Hof, Martin

2014-08-01

Since pharmacokinetic and pharmacodynamic activities of drugs are often related to their interactions with biomembranes, it is of high interest to establish an approach for the characterization of these interactions at the molecular level. For the present study, beta-blockers (oxprenolol, propranolol, and acebutolol) were selected due to their well described nonspecific membrane effects (NME). Their interactions with model lipid membranes composed of palmitoyloleoylphosphatidylcholine (POPC) were studied using Time-Dependent Fluorescence Shift (TDFS) and Generalized Polarization (GP) as well as molecular dynamics (MD) simulations. Liposomal vesicles were labeled with fluorescent membrane polarity probes (Laurdan, Prodan, and Dtmac). Increasing beta-blocker concentrations (0-10 mM for acebutolol and oxprenolol, and 0-1.5 mM for propranolol) significantly rigidifies the lipid bilayer at the glycerol and headgroup level, which was detected in the steady-state and in the time-resolved fluorescence data. The effects of propranolol were considerably stronger than those of the two other beta-blockers. The addition of fluorescent probes precisely located at different levels within the lipid bilayer revealed the insertion of the beta-blockers into the POPC bilayer at the glycerol backbone level, which was further confirmed by MD simulations in the case of propranolol. Copyright © 2014 Elsevier B.V. All rights reserved.

Atomistic Model for the Polyamide Formation from β-Lactam Catalyzed by Candida Antarctica Lipase B

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baum, Iris; Elsasser, Brigitta M.; Schwab, Leendert

2011-04-01

Candida antarctica lipase B (CALB) is an established biocatalyst for a variety of transesterification, amidation, and polymerization reactions. In contrast to polyesters, polyamides are not yet generally accessible via enzymatic polymerization. In this regard, an enzyme-catalyzed ring-opening polymerization of {beta}-lactam (2-azetidinone) using CALB is the first example of an enzymatic polyamide formation yielding unbranched poly({beta}-alanine), nylon 3. The performance of this polymerization, however, is poor, considering the maximum chain length of 18 monomer units with an average length of 8, and the molecular basis of the reaction so far is not understood. We have employed molecular modeling techniques using dockingmore » tools, molecular dynamics, and QM/MM procedures to gain insight into the mechanistic details of the various reaction steps involved. As a result, we propose a catalytic cycle for the oligomerization of {beta}-lactam that rationalizes the activation of the monomer, the chain elongation by additional {beta}-lactam molecules, and the termination of the polymer chain. In addition, the processes leading to a premature chain termination are studied. Particularly, the QM/MM calculation enables an atomistic description of all eight steps involved in the catalytic cycle, which features an in situ-generated {beta}-alanine as the elongating monomer and which is compatible with the experimental findings.« less

Time dependence of volcano inflation: mass influx or viscoelastic relaxation? Insights from Grímsvötn volcano, Iceland

NASA Astrophysics Data System (ADS)

Segall, P.

2017-12-01

Distinguishing magma chamber pressurization from relaxation of a viscoelastic aureole surrounding the chamber based on geodetic measurements has remained challenging. Elastic models with mass inflow proportional to the pressure difference between the chamber and a deep reservoir predict exponentially decaying flux. For a spherical chamber surrounded by a Maxwell viscoelastic shell with pressure dependent recharge, the surface deformation is the sum of two exponentials (Segall, 2016). GPS displacements following eruptions of Grímsvötn, Iceland in 2004 and 2011 exhibit rapid post-eruptive inflation (time scale of 0.1 yr), followed by inflation with a much longer time constant. Markov Chain Monte Carlo inversion with the viscoelastic model shows the GPS time series can be fit with viscosity of 2e16 Pa-s, and a relatively incompressible magma, B = beta_c/ (beta_m + beta_c) > 0.6, where beta_m and beta_c are chamber and magma compressibility. The latter appears to conflict with the ratio of erupted volume to geodetically inferred source volume change, rv 10, obtained for the best fitting spherical (Mogi ) source (Hreinsdóttir, 2014). Since rv = 1/B, this implies a relatively compressible melt, B 0.1. Reexamination of the co-eruptive GPS and tilt data with the more general ellipsoidal model of Cervelli (2013), reveals that the best fitting sources are oblate (b/a 3), deeper, and with larger volume changes, rv 3, relative to spherical models. Oblate magma chambers are consistent with seismic tomography. FEM calculations including free surface effects lead to even larger co-eruptive volume changes, smaller rv and hence larger B. I conclude that the data are consistent with rapid post-eruptive inflation driven by viscoelastic relaxation with a relatively incompressible magma, although other interpretations will be discussed.

The beta Burr type X distribution properties with application.

PubMed

Merovci, Faton; Khaleel, Mundher Abdullah; Ibrahim, Noor Akma; Shitan, Mahendran

2016-01-01

We develop a new continuous distribution called the beta-Burr type X distribution that extends the Burr type X distribution. The properties provide a comprehensive mathematical treatment of this distribution. Further more, various structural properties of the new distribution are derived, that includes moment generating function and the rth moment thus generalizing some results in the literature. We also obtain expressions for the density, moment generating function and rth moment of the order statistics. We consider the maximum likelihood estimation to estimate the parameters. Additionally, the asymptotic confidence intervals for the parameters are derived from the Fisher information matrix. Finally, simulation study is carried at under varying sample size to assess the performance of this model. Illustration the real dataset indicates that this new distribution can serve as a good alternative model to model positive real data in many areas.

A Model for Straight and Helical Solar Jets: II. Parametric Study of the Plasma Beta

NASA Technical Reports Server (NTRS)

Pariat, E.; Dalmasse, K.; DeVore, C. R.; Antiochos, S. K.; Karpen, J. T.

2016-01-01

Context. Jets are dynamic, impulsive, well-collimated plasma events that develop at many different scales and in different layers of the solar atmosphere. Aims. Jets are believed to be induced by magnetic reconnection, a process central to many astrophysical phenomena. Within the solar atmosphere, jet-like events develop in many different environments, e.g. in the vicinity of active regions as well as in coronal holes, and at various scales, from small photospheric spicules to large coronal jets. In all these events, signatures of helical structure and/or twisting/rotating motions are regularly observed. The present study aims to establish that a single model can generally reproduce the observed properties of these jet-like events. Methods. In this study, using our state-of-the-art numerical solver ARMS, we present a parametric study of a numerical tridimensional magnetohydrodynamic (MHD) model of solar jet-like events. Within the MHD paradigm, we study the impact of varying the atmospheric plasma beta on the generation and properties of solar-like jets. Results. The parametric study validates our model of jets for plasma beta ranging from 10(sup 3) to 1, typical of the different layers and magnetic environments of the solar atmosphere. Our model of jets can robustly explain the generation of helical solar jet-like events at various beta less than or equal to 1. We show that the plasma beta modifies the morphology of the helical jet, explaining the different observed shapes of jets at different scales and in different layers of the solar atmosphere. Conclusions. Our results allow us to understand the energisation, triggering, and driving processes of jet-like events. Our model allows us to make predictions of the impulsiveness and energetics of jets as determined by the surrounding environment, as well as the morphological properties of the resulting jets.

Economic benefits associated with beta blocker persistence in the treatment of hypertension: a retrospective database analysis.

PubMed

Chen, Stephanie; Swallow, Elyse; Li, Nanxin; Faust, Elizabeth; Kelley, Caroline; Xie, Jipan; Wu, Eric

2015-04-01

To assess the association between medical costs and persistence with beta blockers among hypertensive patients, and to quantify persistence related medical cost differences with nebivolol, which is associated with improved tolerability, versus other beta blockers. Adults who initiated hypertension treatment with a beta blocker were identified from the MarketScan * claims database (2008-2012). Patients were classified based on their first beta blocker use: nebivolol, atenolol, carvedilol, metoprolol, and other beta blockers. Patients with compelling indications for atenolol, carvedilol or metoprolol (acute coronary syndrome and congestive heart failure) were excluded. Patients enrolled in health maintenance organization or capitated point of service insurance plans were also excluded. Persistence was defined as continuous use of the index drug (<60 day gap). The average effect of persistence on medical costs (2012 USD) was estimated using generalized linear models (GLMs). Regression estimates were used to predict medical cost differences associated with persistence between nebivolol and the other cohorts. A total of 587,424 hypertensive patients met the inclusion criteria. Each additional month of persistence with any one beta blocker was associated with $152.51 in all-cause medical cost savings; continuous treatment for 1 year was associated with $1585.98 in all-cause medical cost savings. Patients treated with nebivolol had longer persistence during the 1 year study period (median: 315 days) than all other beta blockers (median: 156-292 days). Longer persistence with nebivolol translated into $305.74 all-cause medical cost savings relative to all other beta blockers. The results may not be generalizable to hypertensive patients with acute coronary syndrome or congestive heart failure. Longer persistence with beta blockers for the treatment of hypertension was associated with lower medical costs. There may be greater cost savings due to better persistence with nebivolol than other beta blockers.

Human papillomaviruses and skin cancer.

PubMed

Smola, Sigrun

2014-01-01

Human papillomaviruses (HPVs) infect squamous epithelia and can induce hyperproliferative lesions. More than 120 different HPV types have been characterized and classified into five different genera. While mucosal high-risk HPVs have a well-established causal role in anogenital carcinogenesis, the biology of cutaneous HPVs is less well understood. The clinical relevance of genus beta-PV infection has clearly been demonstrated in patients suffering from epidermodysplasia verruciformis (EV), a rare inherited disease associated with ahigh rate of skin cancer. In the normal population genus beta-PV are suspected to have an etiologic role in skin carcinogenesis as well but this is still controversially discussed. Their oncogenic potency has been investigated in mouse models and in vitro. In 2009, the International Agency for Research on Cancer (IARC) classified the genus beta HPV types 5 and 8 as "possible carcinogenic" biological agents (group 2B) in EV disease. This chapter will give an overview on the knowns and unknowns of infections with genus beta-PV and discuss their potential impact on skin carcinogenesis in the general population.

Gay-Berne and electrostatic multipole based coarse-grain potential in implicit solvent

PubMed Central

Wu, Johnny; Zhen, Xia; Shen, Hujun; Li, Guohui; Ren, Pengyu

2011-01-01

A general, transferable coarse-grain (CG) framework based on the Gay-Berne potential and electrostatic point multipole expansion is presented for polypeptide simulations. The solvent effect is described by the Generalized Kirkwood theory. The CG model is calibrated using the results of all-atom simulations of model compounds in solution. Instead of matching the overall effective forces produced by atomic models, the fundamental intermolecular forces such as electrostatic, repulsion-dispersion, and solvation are represented explicitly at a CG level. We demonstrate that the CG alanine dipeptide model is able to reproduce quantitatively the conformational energy of all-atom force fields in both gas and solution phases, including the electrostatic and solvation components. Replica exchange molecular dynamics and microsecond dynamic simulations of polyalanine of 5 and 12 residues reveal that the CG polyalanines fold into “alpha helix” and “beta sheet” structures. The 5-residue polyalanine displays a substantial increase in the “beta strand” fraction relative to the 12-residue polyalanine. The detailed conformational distribution is compared with those reported from recent all-atom simulations and experiments. The results suggest that the new coarse-graining approach presented in this study has the potential to offer both accuracy and efficiency for biomolecular modeling. PMID:22029338

A multiplicative process for generating a beta-like survival function with application to the UK 2016 EU referendum results

NASA Astrophysics Data System (ADS)

Fenner, Trevor; Kaufmann, Eric; Levene, Mark; Loizou, George

Human dynamics and sociophysics suggest statistical models that may explain and provide us with better insight into social phenomena. Contextual and selection effects tend to produce extreme values in the tails of rank-ordered distributions of both census data and district-level election outcomes. Models that account for this nonlinearity generally outperform linear models. Fitting nonlinear functions based on rank-ordering census and election data therefore improves the fit of aggregate voting models. This may help improve ecological inference, as well as election forecasting in majoritarian systems. We propose a generative multiplicative decrease model that gives rise to a rank-order distribution and facilitates the analysis of the recent UK EU referendum results. We supply empirical evidence that the beta-like survival function, which can be generated directly from our model, is a close fit to the referendum results, and also may have predictive value when covariate data are available.

Creating Synthetic Coronal Observational Data From MHD Models: The Forward Technique

NASA Technical Reports Server (NTRS)

Rachmeler, Laurel A.; Gibson, Sarah E.; Dove, James; Kucera, Therese Ann

2010-01-01

We present a generalized forward code for creating simulated corona) observables off the limb from numerical and analytical MHD models. This generalized forward model is capable of creating emission maps in various wavelengths for instruments such as SXT, EIT, EIS, and coronagraphs, as well as spectropolari metric images and line profiles. The inputs to our code can be analytic models (of which four come with the code) or 2.5D and 3D numerical datacubes. We present some examples of the observable data created with our code as well as its functional capabilities. This code is currently available for beta-testing (contact authors), with the ultimate goal of release as a SolarSoft package

40 CFR 180.157 - Methyl 3-[(dimethoxyphos-phinyl) oxy]butenoate, alpha and beta isomers; tolerances for residues.

Code of Federal Regulations, 2010 CFR

2010-07-01

...]butenoate, alpha and beta isomers; tolerances for residues. 180.157 Section 180.157 Protection of...]butenoate, alpha and beta isomers; tolerances for residues. (a) General. Tolerances are established for residues of the insecticide methyl 3-[(dimethoxyphosphinyl)oxy]butenoate, alpha and beta isomers, in or on...

40 CFR 180.157 - Methyl 3-[(dimethoxyphos-phinyl) oxy]butenoate, alpha and beta isomers; tolerances for residues.

Code of Federal Regulations, 2011 CFR

2011-07-01

...]butenoate, alpha and beta isomers; tolerances for residues. 180.157 Section 180.157 Protection of...]butenoate, alpha and beta isomers; tolerances for residues. (a) General. Tolerances are established for residues of the insecticide methyl 3-[(dimethoxyphosphinyl)oxy]butenoate, alpha and beta isomers, in or on...

Modeling the Production of Beta-Delayed Gamma Rays for the Detection of Special Nuclear Materials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hall, J M; Pruet, J A; Brown, D A

2005-02-14

The objective of this LDRD project was to develop one or more models for the production of {beta}-delayed {gamma} rays following neutron-induced fission of a special nuclear material (SNM) and to define a standardized formatting scheme which will allow them to be incorporated into some of the modern, general-purpose Monte Carlo transport codes currently being used to simulate inspection techniques proposed for detecting fissionable material hidden in sea-going cargo containers. In this report, we will describe a Monte Carlo model for {beta}-delayed {gamma}-ray emission following the fission of SNM that can accommodate arbitrary time-dependent fission rates and photon collection histories.more » The model involves direct sampling of the independent fission yield distributions of the system, the branching ratios for decay of individual fission products and spectral distributions representing photon emission from each fission product and for each decay mode. While computationally intensive, it will be shown that this model can provide reasonably detailed estimates of the spectra that would be recorded by an arbitrary spectrometer and may prove quite useful in assessing the quality of evaluated data libraries and identifying gaps in the libraries. The accuracy of the model will be illustrated by comparing calculated and experimental spectra from the decay of short-lived fission products following the reactions {sup 235}U(n{sub th}, f) and {sup 239}Pu(n{sub th}, f). For general-purpose transport calculations, where a detailed consideration of the large number of individual {gamma}-ray transitions in a spectrum may not be necessary, it will be shown that a simple parameterization of the {gamma}-ray source function can be defined which provides high-quality average spectral distributions that should suffice for calculations describing photons being transported through thick attenuating media. Finally, a proposal for ENDF-compatible formats that describe each of the models and allow for their straightforward use in Monte Carlo codes will be presented.« less

Cartilage acidic protein 1, a new member of the beta-propeller protein family with amyloid propensity.

PubMed

Anjos, Liliana; Morgado, Isabel; Guerreiro, Marta; Cardoso, João C R; Melo, Eduardo P; Power, Deborah M

2017-02-01

Cartilage acidic protein1 (CRTAC1) is an extracellular matrix protein of chondrogenic tissue in humans and its presence in bacteria indicate it is of ancient origin. Structural modeling of piscine CRTAC1 reveals it belongs to the large family of beta-propeller proteins that in mammals have been associated with diseases, including amyloid diseases such as Alzheimer's. In order to characterize the structure/function evolution of this new member of the beta-propeller family we exploited the unique characteristics of piscine duplicate genes Crtac1a and Crtac1b and compared their structural and biochemical modifications with human recombinant CRTAC1. We demonstrate that CRTAC1 has a beta-propeller structure that has been conserved during evolution and easily forms high molecular weight thermo-stable aggregates. We reveal for the first time the propensity of CRTAC1 to form amyloid-like structures, and hypothesize that the aggregating property of CRTAC1 may be related to its disease-association. We further contribute to the general understating of CRTAC1's and beta-propeller family evolution and function. Proteins 2017; 85:242-255. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Reduced Fragment Diversity for Alpha and Alpha-Beta Protein Structure Prediction using Rosetta.

PubMed

Abbass, Jad; Nebel, Jean-Christophe

2017-01-01

Protein structure prediction is considered a main challenge in computational biology. The biannual international competition, Critical Assessment of protein Structure Prediction (CASP), has shown in its eleventh experiment that free modelling target predictions are still beyond reliable accuracy, therefore, much effort should be made to improve ab initio methods. Arguably, Rosetta is considered as the most competitive method when it comes to targets with no homologues. Relying on fragments of length 9 and 3 from known structures, Rosetta creates putative structures by assembling candidate fragments. Generally, the structure with the lowest energy score, also known as first model, is chosen to be the "predicted one". A thorough study has been conducted on the role and diversity of 3-mers involved in Rosetta's model "refinement" phase. Usage of the standard number of 3-mers - i.e. 200 - has been shown to degrade alpha and alpha-beta protein conformations initially achieved by assembling 9-mers. Therefore, a new prediction pipeline is proposed for Rosetta where the "refinement" phase is customised according to a target's structural class prediction. Over 8% improvement in terms of first model structure accuracy is reported for alpha and alpha-beta classes when decreasing the number of 3- mers. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Application of nuclear magnetic resonance spectroscopy, Fourier transform infrared spectroscopy, UV-Visible spectroscopy and kinetic modeling for elucidation of adsorption chemistry in uptake of tetracycline by zeolite beta.

PubMed

Kang, Jin; Liu, Huijuan; Zheng, Yu-Ming; Qu, Jiuhui; Chen, J Paul

2011-02-01

Extensive usage of tetracycline has resulted in its contamination in surface water and groundwater. The adsorption of tetracycline on zeolite beta was systematically investigated for the decontamination of the antibiotic polluted water in this study. Ninety percent of uptake by the zeolite beta occured in 0.25h, and the adsorption equilibrium was obtained within 3h, which was well described by an intraparticle diffusion model. The adsorption generally increased when pH was increased from 4.0 to 5.0, and then decreased significantly as the pH was further increased, which was caused by the pH-dependent speciation of tetracycline and surface charge of zeolite beta. Both Freundlich and Langmuir equations well described the adsorption isotherm. A thermodynamic analysis showed that the sorption process was spontaneous and endothermic. Aluminum atoms in the zeolite played a crucial role in the uptake; the adsorption increased with the increasing aluminum content in zeolite. The UV-Visible spectroscopy study showed that the spectra of tetracycline changed upon the interaction with zeolite beta, which could be ascribed to the formation of complexes of tetracycline and aluminum atoms in the zeolite surface. Nuclear magnetic resonance spectroscopy study further confirmed the participation of Al in the tetracycline adsorption. Fourier transform infrared spectroscopy studies showed that the amino functional groups in tetracycline were involved in the complexation with the zeolite surface. Copyright © 2010 Elsevier Inc. All rights reserved.

Local-scale Partitioning of Functional and Phylogenetic Beta Diversity in a Tropical Tree Assemblage.

PubMed

Yang, Jie; Swenson, Nathan G; Zhang, Guocheng; Ci, Xiuqin; Cao, Min; Sha, Liqing; Li, Jie; Ferry Slik, J W; Lin, Luxiang

2015-08-03

The relative degree to which stochastic and deterministic processes underpin community assembly is a central problem in ecology. Quantifying local-scale phylogenetic and functional beta diversity may shed new light on this problem. We used species distribution, soil, trait and phylogenetic data to quantify whether environmental distance, geographic distance or their combination are the strongest predictors of phylogenetic and functional beta diversity on local scales in a 20-ha tropical seasonal rainforest dynamics plot in southwest China. The patterns of phylogenetic and functional beta diversity were generally consistent. The phylogenetic and functional dissimilarity between subplots (10 × 10 m, 20 × 20 m, 50 × 50 m and 100 × 100 m) was often higher than that expected by chance. The turnover of lineages and species function within habitats was generally slower than that across habitats. Partitioning the variation in phylogenetic and functional beta diversity showed that environmental distance was generally a better predictor of beta diversity than geographic distance thereby lending relatively more support for deterministic environmental filtering over stochastic processes. Overall, our results highlight that deterministic processes play a stronger role than stochastic processes in structuring community composition in this diverse assemblage of tropical trees.

Energy-confinement scaling for high-beta plasmas in the W7-AS stellarator.

PubMed

Preuss, R; Dinklage, A; Weller, A

2007-12-14

High-beta energy-confinement data are subjected to comparisons of scaling invariant, first-principles physical models. The models differ in the inclusion of basic equations indicating the nature of transport. The result for high-beta data of the W7-AS stellarator is that global transport is described best with a collisional high-beta model, which is different from previous outcomes for low-beta data. Model predictive calculations indicate the validation of energy-confinement prediction with respect to plasma beta and collisionality nu*. The finding of different transport behaviors in distinct beta regimes is important for the development of fusion energy based on magnetic confinement and for the assessment of different confinement concepts.

Interpreting Regression Results: beta Weights and Structure Coefficients are Both Important.

ERIC Educational Resources Information Center

Thompson, Bruce

Various realizations have led to less frequent use of the "OVA" methods (analysis of variance--ANOVA--among others) and to more frequent use of general linear model approaches such as regression. However, too few researchers understand all the various coefficients produced in regression. This paper explains these coefficients and their…

The Use of Structure Coefficients to Address Multicollinearity in Sport and Exercise Science

ERIC Educational Resources Information Center

Yeatts, Paul E.; Barton, Mitch; Henson, Robin K.; Martin, Scott B.

2017-01-01

A common practice in general linear model (GLM) analyses is to interpret regression coefficients (e.g., standardized ß weights) as indicators of variable importance. However, focusing solely on standardized beta weights may provide limited or erroneous information. For example, ß weights become increasingly unreliable when predictor variables are…

Predicting diffusion paths and interface motion in gamma/gamma + beta, Ni-Cr-Al diffusion couples

NASA Technical Reports Server (NTRS)

Nesbitt, J. A.; Heckel, R. W.

1987-01-01

A simplified model has been developed to predict Beta recession and diffusion paths in ternary gamma/gamma + beta diffusion couples (gamma:fcc, beta: NiAl structure). The model was tested by predicting beta recession and diffusion paths for four gamma/gamma + beta, Ni-Cr-Al couples annealed for 100 hours at 1200 C. The model predicted beta recession within 20 percent of that measured for each of the couples. The model also predicted shifts in the concentration of the gamma phase at the gamma/gamma + beta interface within 2 at. pct Al and 6 at. pct Cr of that measured in each of the couples. A qualitative explanation based on simple kinetic and mass balance arguments has been given which demonstrates the necessity for diffusion in the two-phase region of certain gamma/gamma + beta, Ni-Cr-Al couples.

Order-disorder transition in conflicting dynamics leading to rank-frequency generalized beta distributions

NASA Astrophysics Data System (ADS)

Alvarez-Martinez, R.; Martinez-Mekler, G.; Cocho, G.

2011-01-01

The behavior of rank-ordered distributions of phenomena present in a variety of fields such as biology, sociology, linguistics, finance and geophysics has been a matter of intense research. Often power laws have been encountered; however, their validity tends to hold mainly for an intermediate range of rank values. In a recent publication (Martínez-Mekler et al., 2009 [7]), a generalization of the functional form of the beta distribution has been shown to give excellent fits for many systems of very diverse nature, valid for the whole range of rank values, regardless of whether or not a power law behavior has been previously suggested. Here we give some insight on the significance of the two free parameters which appear as exponents in the functional form, by looking into discrete probabilistic branching processes with conflicting dynamics. We analyze a variety of realizations of these so-called expansion-modification models first introduced by Wentian Li (1989) [10]. We focus our attention on an order-disorder transition we encounter as we vary the modification probability p. We characterize this transition by means of the fitting parameters. Our numerical studies show that one of the fitting exponents is related to the presence of long-range correlations exhibited by power spectrum scale invariance, while the other registers the effect of disordering elements leading to a breakdown of these properties. In the absence of long-range correlations, this parameter is sensitive to the occurrence of unlikely events. We also introduce an approximate calculation scheme that relates this dynamics to multinomial multiplicative processes. A better understanding through these models of the meaning of the generalized beta-fitting exponents may contribute to their potential for identifying and characterizing universality classes.

Self-consistent asset pricing models

NASA Astrophysics Data System (ADS)

Malevergne, Y.; Sornette, D.

2007-08-01

We discuss the foundations of factor or regression models in the light of the self-consistency condition that the market portfolio (and more generally the risk factors) is (are) constituted of the assets whose returns it is (they are) supposed to explain. As already reported in several articles, self-consistency implies correlations between the return disturbances. As a consequence, the alphas and betas of the factor model are unobservable. Self-consistency leads to renormalized betas with zero effective alphas, which are observable with standard OLS regressions. When the conditions derived from internal consistency are not met, the model is necessarily incomplete, which means that some sources of risk cannot be replicated (or hedged) by a portfolio of stocks traded on the market, even for infinite economies. Analytical derivations and numerical simulations show that, for arbitrary choices of the proxy which are different from the true market portfolio, a modified linear regression holds with a non-zero value αi at the origin between an asset i's return and the proxy's return. Self-consistency also introduces “orthogonality” and “normality” conditions linking the betas, alphas (as well as the residuals) and the weights of the proxy portfolio. Two diagnostics based on these orthogonality and normality conditions are implemented on a basket of 323 assets which have been components of the S&P500 in the period from January 1990 to February 2005. These two diagnostics show interesting departures from dynamical self-consistency starting about 2 years before the end of the Internet bubble. Assuming that the CAPM holds with the self-consistency condition, the OLS method automatically obeys the resulting orthogonality and normality conditions and therefore provides a simple way to self-consistently assess the parameters of the model by using proxy portfolios made only of the assets which are used in the CAPM regressions. Finally, the factor decomposition with the self-consistency condition derives a risk-factor decomposition in the multi-factor case which is identical to the principal component analysis (PCA), thus providing a direct link between model-driven and data-driven constructions of risk factors. This correspondence shows that PCA will therefore suffer from the same limitations as the CAPM and its multi-factor generalization, namely lack of out-of-sample explanatory power and predictability. In the multi-period context, the self-consistency conditions force the betas to be time-dependent with specific constraints.

Beta-cryptoxanthin: A vitamin A-forming carotenoid

USDA-ARS?s Scientific Manuscript database

Beta-cryptoxanthin is a common carotenoid. It is generally the fourth most abundant in human blood but can achieve high concentrations especially in Japanese and Spanish populations. Its richest food sources include mandarin oranges, persimmons, oranges, papayas, pumpkin, and red sweet peppers. Beta...

Comparative study of generalized born models: Born radii and peptide folding.

PubMed

Zhu, Jiang; Alexov, Emil; Honig, Barry

2005-02-24

In this study, we have implemented four analytical generalized Born (GB) models and investigated their performance in conjunction with the GROMOS96 force field. The four models include that of Still and co-workers, the HCT model of Cramer, Truhlar, and co-workers, a modified form of the AGB model of Levy and co-workers, and the GBMV2 model of Brooks and co-workers. The models were coded independently and implemented in the GROMOS software package and in TINKER. They were compared in terms of their ability to reproduce the results of Poisson-Boltzmann (PB) calculations and in their performance in the ab initio peptide folding of two peptides, one that forms a beta-hairpin in solution and one that forms an alpha-helix. In agreement with previous work, the GBMV2 model is most successful in reproducing PB results while the other models tend to underestimate the effective Born radii of buried atoms. In contrast, stochastic dynamics simulations on the folding of the two peptides, the C-terminus beta-hairpin of the B1 domain of protein G and the alanine-based alpha-helical peptide 3K(I), suggest that the simpler GB models are more effective in sampling conformational space. Indeed, the Still model used in conjunction with the GROMOS96 force field is able to fold the hairpin peptide to a native-like structure without the benefit of enhanced sampling techniques. This is due in part to the properties of the united-atom GROMOS96 force field which appears to be more flexible, and hence to sample more efficiently, than force fields such as OPLSAA. Our results suggest a general strategy which involves using different combinations of force fields and solvent models in different applications, for example, using GROMOS96 and a simple GB model in sampling and OPLSAA and a more accurate GB model in refinement. The fact that various methods have been implemented in a unified way should facilitate the testing and subsequent use of different methods to evaluate conformational free energies in different applications. Our results also bear on some general issues involved in peptide folding and structure prediction which are addressed in the Discussion.

Cell kill by megavoltage protons with high LET.

PubMed

Kuperman, Vadim Y

2016-07-21

The aim of the current study is to develop a radiobiological model which describes the effect of linear energy transfer (LET) on cell survival and relative biological effectiveness (RBE) of megavoltage protons. By assuming the existence of critical sites within a cell, analytical expression for cell survival S as a function of LET is derived. The obtained results indicate that in cases where dose per fraction is small, [Formula: see text] is a linear-quadratic (LQ) function of dose while both alpha and beta radio-sensitivities are non-linearly dependent on LET. In particular, in the current model alpha increases with increasing LET while beta decreases. Conversely, in the case of large dose per fraction, the LQ dependence of [Formula: see text] on dose is invalid. The proposed radiobiological model predicts cell survival probability and RBE which, in general, deviate from the results obtained by using conventional LQ formalism. The differences between the LQ model and that described in the current study are reflected in the calculated RBE of protons.

Tolerability to beta-blocker therapy among heart failure patients in clinical practice.

PubMed

Butler, Javed; Khadim, Ghazanfar; Belue, Rhonda; Chomsky, Don; Dittus, Robert S; Griffin, Marie; Wilson, John R

2003-06-01

Although beta-blockers were well-tolerated by heart failure (HF) patients in clinical trials, tolerability of these drugs in a general population of HF patients is not well-described. We studied a total of 308 encounters with beta-blockers therapy in 268 ambulatory HF patients. Side effects and frequency and predictors of discontinuation of therapy were studied. Independent predictors of discontinuation were assessed. Weight gain (59%), fatigue (56%), dizziness (41%), and dyspnea (29%) were the most common side effects. Fifty-one patients (19%) were discontinued on therapy with any 1 particular beta-blocker. Fatigue (30%) and hypotension (28%) were the most common reasons for discontinuation. Forty (78%) of these were given a trial with a different beta-blocker. Of these, 22 (55%) attempts with a different beta-blocker were tolerated. Thus the overall absolute discontinuation rate was only 7% for patients who were given a trial with different beta-blockers or 11% for the entire study population. Independent predictors of discontinuation of therapy included advanced symptoms, nonischemic etiology, history of pulmonary disease, and higher diuretic doses. Side effects with beta-blockers in a general population of HF patients are common; however, with changes in medical management, most patients can tolerate them eventually. In case of intolerance to one kind, a trial with a different beta-blocker is indicated.

Re-evaluating the efficacy of beta-adrenergic agonists and antagonists in long QT-3 syndrome through computational modelling.

PubMed

Ahrens-Nicklas, Rebecca C; Clancy, Colleen E; Christini, David J

2009-06-01

Long QT syndrome (LQTS) is a heterogeneous collection of inherited cardiac ion channelopathies characterized by a prolonged electrocardiogram QT interval and increased risk of sudden cardiac death. Beta-adrenergic blockers are the mainstay of treatment for LQTS. While their efficacy has been demonstrated in LQTS patients harbouring potassium channel mutations, studies of beta-blockers in subtype 3 (LQT3), which is caused by sodium channel mutations, have produced ambiguous results. In this modelling study, we explore the effects of beta-adrenergic drugs on the LQT3 phenotype. In order to investigate the effects of beta-adrenergic activity and to identify sources of ambiguity in earlier studies, we developed a computational model incorporating the effects of beta-agonists and beta-blockers into an LQT3 mutant guinea pig ventricular myocyte model. Beta-activation suppressed two arrhythmogenic phenomena, transmural dispersion of repolarization and early after depolarizations, in a dose-dependent manner. However, the ability of beta-activation to prevent cardiac conduction block was pacing-rate-dependent. Low-dose beta-blockade by propranolol reversed the beneficial effects of beta-activation, while high dose (which has off-target sodium channel effects) decreased arrhythmia susceptibility. These results demonstrate that beta-activation may be protective in LQT3 and help to reconcile seemingly conflicting results from different experimental models. They also highlight the need for well-controlled clinical investigations re-evaluating the use of beta-blockers in LQT3 patients.

The re-incarnation, re-interpretation and re-demise of the transition probability model.

PubMed

Koch, A L

1999-05-28

There are two classes of models for the cell cycle that have both a deterministic and a stochastic part; they are the transition probability (TP) models and sloppy size control (SSC) models. The hallmark of the basic TP model are two graphs: the alpha and beta plots. The former is the semi-logarithmic plot of the percentage of cell divisions yet to occur, this results in a horizontal line segment at 100% corresponding to the deterministic phase and a straight line sloping tail corresponding to the stochastic part. The beta plot concerns the differences of the age-at-division of sisters (the beta curve) and gives a straight line parallel to the tail of the alpha curve. For the SC models the deterministic part is the time needed for the cell to accumulate a critical amount of some substance(s). The variable part differs in the various variants of the general model, but they do not give alpha and beta curves with linear tails as postulated by the TP model. This paper argues against TP and for an elaboration of SSC type of model. The main argument against TP is that it assumes that the probability of the transition from the stochastic phase is time invariant even though it is certain that the cells are growing and metabolizing throughout the cell cycle; a fact that should make the transition probability be variable. The SSC models presume that cell division is triggered by the cell's success in growing and not simply the result of elapsed time. The extended model proposed here to accommodate the predictions of the SSC to the straight tailed parts of the alpha and beta plots depends on the existence of a few percent of the cell in a growing culture that are not growing normally, these are growing much slower or are temporarily quiescent. The bulk of the cells, however, grow nearly exponentially. Evidence for a slow growing component comes from experimental analyses of population size distributions for a variety of cell types by the Collins-Richmond technique. These subpopulations existence is consistent with the new concept that there are a large class of rapidly reversible mutations occurring in many organisms and at many loci serving a large range of purposes to enable the cell to survive environmental challenges. These mutations yield special subpopulations of cells within a population. The reversible mutational changes, relevant to the elaboration of SSC models, produce slow-growing cells that are either very large or very small in size; these later revert to normal growth and division. The subpopulations, however, distort the population distribution in such a way as to fit better the exponential tails of the alpha and beta curves of the TP model.

Neural mechanisms of transient neocortical beta rhythms: Converging evidence from humans, computational modeling, monkeys, and mice.

PubMed

Sherman, Maxwell A; Lee, Shane; Law, Robert; Haegens, Saskia; Thorn, Catherine A; Hämäläinen, Matti S; Moore, Christopher I; Jones, Stephanie R

2016-08-16

Human neocortical 15-29-Hz beta oscillations are strong predictors of perceptual and motor performance. However, the mechanistic origin of beta in vivo is unknown, hindering understanding of its functional role. Combining human magnetoencephalography (MEG), computational modeling, and laminar recordings in animals, we present a new theory that accounts for the origin of spontaneous neocortical beta. In our MEG data, spontaneous beta activity from somatosensory and frontal cortex emerged as noncontinuous beta events typically lasting <150 ms with a stereotypical waveform. Computational modeling uniquely designed to infer the electrical currents underlying these signals showed that beta events could emerge from the integration of nearly synchronous bursts of excitatory synaptic drive targeting proximal and distal dendrites of pyramidal neurons, where the defining feature of a beta event was a strong distal drive that lasted one beta period (∼50 ms). This beta mechanism rigorously accounted for the beta event profiles; several other mechanisms did not. The spatial location of synaptic drive in the model to supragranular and infragranular layers was critical to the emergence of beta events and led to the prediction that beta events should be associated with a specific laminar current profile. Laminar recordings in somatosensory neocortex from anesthetized mice and awake monkeys supported these predictions, suggesting this beta mechanism is conserved across species and recording modalities. These findings make several predictions about optimal states for perceptual and motor performance and guide causal interventions to modulate beta for optimal function.

Testing atomic mass models with radioactive beams

DOE Office of Scientific and Technical Information (OSTI.GOV)

Haustein, P.E.

1989-01-01

Significantly increased yields of new or poorly characterized exotic isotopes that lie far from beta-decay stability can be expected when radioactive beams are used to produce these nuclides. Measurements of the masses of these new species are very important. Such measurements are motivated by the general tendency of mass models to diverge from one another upon excursions from the line of beta-stability. Therefore in these regions (where atomic mass data are presently nonexistent or sparse) the models can be tested rigorously to highlight the features that affect the quality of their short-range and long-range extrapolation properties. Selection of systems tomore » study can be guided, in part, by a desire to probe those mass regions where distinctions among mass models are most apparent and where yields of exotic isotopes, produced via radioactive beams, can be optimized. Identification of models in such regions that have good predictive properties will aid materially in guiding the selection of additional experiments which ultimately will provide expansion of the atomic mass database for further refinement of the mass models. 6 refs., 5 figs.« less

Beta-Poisson model for single-cell RNA-seq data analyses.

PubMed

Vu, Trung Nghia; Wills, Quin F; Kalari, Krishna R; Niu, Nifang; Wang, Liewei; Rantalainen, Mattias; Pawitan, Yudi

2016-07-15

Single-cell RNA-sequencing technology allows detection of gene expression at the single-cell level. One typical feature of the data is a bimodality in the cellular distribution even for highly expressed genes, primarily caused by a proportion of non-expressing cells. The standard and the over-dispersed gamma-Poisson models that are commonly used in bulk-cell RNA-sequencing are not able to capture this property. We introduce a beta-Poisson mixture model that can capture the bimodality of the single-cell gene expression distribution. We further integrate the model into the generalized linear model framework in order to perform differential expression analyses. The whole analytical procedure is called BPSC. The results from several real single-cell RNA-seq datasets indicate that ∼90% of the transcripts are well characterized by the beta-Poisson model; the model-fit from BPSC is better than the fit of the standard gamma-Poisson model in > 80% of the transcripts. Moreover, in differential expression analyses of simulated and real datasets, BPSC performs well against edgeR, a conventional method widely used in bulk-cell RNA-sequencing data, and against scde and MAST, two recent methods specifically designed for single-cell RNA-seq data. An R package BPSC for model fitting and differential expression analyses of single-cell RNA-seq data is available under GPL-3 license at https://github.com/nghiavtr/BPSC CONTACT: yudi.pawitan@ki.se or mattias.rantalainen@ki.se Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Learning from Higgs physics at future Higgs factories

DOE PAGES

Gu, Jiayin; Li, Honglei; Liu, Zhen; ...

2017-12-29

Future Higgs factories can reach impressive precision on Higgs property measurements. In this paper, instead of conventional focus of Higgs precision in certain interaction bases, we explored its sensitivity to new physics models at the electron-positron colliders. In particular, we studied two categories of new physics models, Standard Model (SM) with a real scalar singlet extension, and Two Higgs Double Model (2HDM) as examples of weakly-interacting models, Minimal Composite Higgs Model (MCHM) and three typical patterns of the more general operator counting for strong interacting models as examples of strong dynamics. We performed a global fit to various Higgs searchmore » channels to obtain the 95% C.L. constraints on the model parameter space. In the SM with a singlet extension, we obtained the limits on the singlet-doublet mixing angle sin(theta), as well as the more general Wilson coefficients of the induced higher dimensional operators. In the 2HDM, we analyzed tree level effects in tan(beta) vs. cos(beta-alpha) plane, as well as the one-loop contributions from the heavy Higgs bosons in the alignment limit to obtain the constraints on heavy Higgs masses for different types of 2HDM. In strong dynamics models, we obtained lower limits on the strong dynamics scale. In addition, once deviations of Higgs couplings are observed, they can be used to distinguish different models. Here, we also compared the sensitivity of various future Higgs factories, namely Circular Electron Positron Collider (CEPC), Future Circular Collider (FCC)-ee and International Linear Collider (ILC).« less

Learning from Higgs physics at future Higgs factories

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gu, Jiayin; Li, Honglei; Liu, Zhen

Future Higgs factories can reach impressive precision on Higgs property measurements. In this paper, instead of conventional focus of Higgs precision in certain interaction bases, we explored its sensitivity to new physics models at the electron-positron colliders. In particular, we studied two categories of new physics models, Standard Model (SM) with a real scalar singlet extension, and Two Higgs Double Model (2HDM) as examples of weakly-interacting models, Minimal Composite Higgs Model (MCHM) and three typical patterns of the more general operator counting for strong interacting models as examples of strong dynamics. We performed a global fit to various Higgs searchmore » channels to obtain the 95% C.L. constraints on the model parameter space. In the SM with a singlet extension, we obtained the limits on the singlet-doublet mixing angle sin(theta), as well as the more general Wilson coefficients of the induced higher dimensional operators. In the 2HDM, we analyzed tree level effects in tan(beta) vs. cos(beta-alpha) plane, as well as the one-loop contributions from the heavy Higgs bosons in the alignment limit to obtain the constraints on heavy Higgs masses for different types of 2HDM. In strong dynamics models, we obtained lower limits on the strong dynamics scale. In addition, once deviations of Higgs couplings are observed, they can be used to distinguish different models. Here, we also compared the sensitivity of various future Higgs factories, namely Circular Electron Positron Collider (CEPC), Future Circular Collider (FCC)-ee and International Linear Collider (ILC).« less

Habitat heterogeneity drives the geographical distribution of beta diversity: the case of New Zealand stream invertebrates.

PubMed

Astorga, Anna; Death, Russell; Death, Fiona; Paavola, Riku; Chakraborty, Manas; Muotka, Timo

2014-07-01

To define whether the beta diversity of stream invertebrate communities in New Zealand exhibits geographical variation unexplained by variation in gamma diversity and, if so, what mechanisms (productivity, habitat heterogeneity, dispersal limitation, disturbance) best explain the observed broad-scale beta diversity patterns. We sampled 120 streams across eight regions (stream catchments), spanning a north-south gradient of 12° of latitude, and calculated beta diversity (with both species richness and abundance data) for each region. We explored through a null model if beta diversity deviates from the expectation of stochastic assembly processes and whether the magnitude of the deviation varies geographically. We then performed multimodel inference analysis on the key environmental drivers of beta diversity, using Akaike's information criterion and model and predictor weights to select the best model(s) explaining beta diversity. Beta diversity was, unexpectedly, highest in the South Island. The null model analysis revealed that beta diversity was greater than expected by chance in all eight regions, but the magnitude of beta deviation was higher in the South Island, suggesting differences in environmental filtering and/or dispersal limitation between North and South Island. Habitat heterogeneity was the predominant driver of beta diversity of stream macroinvertebrates, with productivity having a secondary, and negative, contribution. This is one of the first studies accounting for stochastic effects while examining the ecological drivers of beta diversity. Our results suggest that local environmental heterogeneity may be the strongest determinant of beta diversity of stream invertebrates, more so than regional- or landscape-scale variables.

Competing Mechanisms of Gamma and Beta Oscillations in the Olfactory Bulb Based on Multimodal Inhibition of Mitral Cells Over a Respiratory Cycle123

PubMed Central

Courtiol, Emmanuelle; Buonviso, Nathalie

2015-01-01

Gamma (∼40-90 Hz) and beta (∼15-40 Hz) oscillations and their associated neuronal assemblies are key features of neuronal sensory processing. However, the mechanisms involved in either their interaction and/or the switch between these different regimes in most sensory systems remain misunderstood. Based on in vivo recordings and biophysical modeling of the mammalian olfactory bulb (OB), we propose a general scheme where OB internal dynamics can sustain two distinct dynamic states, each dominated by either a gamma or a beta regime. The occurrence of each regime depends on the excitability level of granule cells, the main OB interneurons. Using this model framework, we demonstrate how the balance between sensory and centrifugal input can control the switch between the two oscillatory dynamic states. In parallel, we experimentally observed that sensory and centrifugal inputs to the rat OB could both be modulated by the respiration of the animal (2-12 Hz) and each one phase shifted with the other. Implementing this phase shift in our model resulted in the appearance of the alternation between gamma and beta rhythms within a single respiratory cycle, as in our experimental results under urethane anesthesia. Our theoretical framework can also account for the oscillatory frequency response, depending on the odor intensity, the odor valence, and the animal sniffing strategy observed under various conditions including animal freely-moving. Importantly, the results of the present model can form a basis to understand how fast rhythms could be controlled by the slower sensory and centrifugal modulations linked to the respiration. Visual Abstract: See Abstract PMID:26665163

Influence of food acidulants and antioxidant spices on the bioaccessibility of beta-carotene from selected vegetables.

PubMed

Veda, Supriya; Platel, Kalpana; Srinivasan, Krishnapura

2008-09-24

Four common food acidulants--amchur, lime, tamarind, and kokum--and two antioxidant spices--turmeric and onion--were examined for their influence on the bioaccessibility of beta-carotene from two fleshy and two leafy vegetables. Amchur and lime generally enhanced the bioaccessibility of beta-carotene from these test vegetables in many instances. Such an improved bioaccessibility was evident in both raw and heat-processed vegetables. The effect of lime juice was generally more pronounced than that of amchur. Turmeric significantly enhanced the bioaccessibility of beta-carotene from all of the vegetables tested, especially when heat-processed. Onion enhanced the bioaccessibility of beta-carotene from pressure-cooked carrot and amaranth leaf and from open-pan-boiled pumpkin and fenugreek leaf. Lime juice and the antioxidant spices turmeric and onion minimized the loss of beta-carotene during heat processing of the vegetables. In the case of antioxidant spices, improved bioaccessibility of beta-carotene from heat-processed vegetables is attributable to their role in minimizing the loss of this provitamin. Lime juice, which enhanced the bioaccessibility of this provitamin from both raw and heat-processed vegetables, probably exerted this effect by some other mechanism in addition to minimizing the loss of beta-carotene. Thus, the presence of food acidulants (lime juice/amchur) and antioxidant spices (turmeric/onion) proved to be advantageous in the context of deriving maximum beta-carotene from the vegetable sources.

The CKM Matrix and The Unitarity Triangle: Another Look

NASA Astrophysics Data System (ADS)

Buras, Andrzej J.; Parodi, Fabrizio; Stocchi, Achille

2003-01-01

The unitarity triangle can be determined by means of two measurements of its sides or angles. Assuming the same relative errors on the angles (alpha,beta,gamma) and the sides (Rb,Rt), we find that the pairs (gamma,beta) and (gamma,Rb) are most efficient in determining (bar varrho,bar eta) that describe the apex of the unitarity triangle. They are followed by (alpha,beta), (alpha,Rb), (Rt,beta), (Rt,Rb) and (Rb,beta). As the set |Vus|, |Vcb|, Rt and beta appears to be the best candidate for the fundamental set of flavour violating parameters in the coming years, we show various constraints on the CKM matrix in the (Rt,beta) plane. Using the best available input we determine the universal unitarity triangle for models with minimal flavour violation (MFV) and compare it with the one in the Standard Model. We present allowed ranges for sin 2beta, sin 2alpha, gamma, Rb, Rt and DeltaMs within the Standard Model and MFV models. We also update the allowed range for the function Ftt that parametrizes various MFV-models.

Investigation on the individual contributions of N-H...O=C and C-H...O=C interactions to the binding energies of beta-sheet models.

PubMed

Wang, Chang-Sheng; Sun, Chang-Liang

2010-04-15

In this article, the binding energies of 16 antiparallel and parallel beta-sheet models are estimated using the analytic potential energy function we proposed recently and the results are compared with those obtained from MP2, AMBER99, OPLSAA/L, and CHARMM27 calculations. The comparisons indicate that the analytic potential energy function can produce reasonable binding energies for beta-sheet models. Further comparisons suggest that the binding energy of the beta-sheet models might come mainly from dipole-dipole attractive and repulsive interactions and VDW interactions between the two strands. The dipole-dipole attractive and repulsive interactions are further obtained in this article. The total of N-H...H-N and C=O...O=C dipole-dipole repulsive interaction (the secondary electrostatic repulsive interaction) in the small ring of the antiparallel beta-sheet models is estimated to be about 6.0 kcal/mol. The individual N-H...O=C dipole-dipole attractive interaction is predicted to be -6.2 +/- 0.2 kcal/mol in the antiparallel beta-sheet models and -5.2 +/- 0.6 kcal/mol in the parallel beta-sheet models. The individual C(alpha)-H...O=C attractive interaction is -1.2 +/- 0.2 kcal/mol in the antiparallel beta-sheet models and -1.5 +/- 0.2 kcal/mol in the parallel beta-sheet models. These values are important in understanding the interactions at protein-protein interfaces and developing a more accurate force field for peptides and proteins. 2009 Wiley Periodicals, Inc.

Micro-power dissipation device described

NASA Astrophysics Data System (ADS)

Mao, X.; Zhou, L.; Zhou, J.

1985-11-01

The common-emitter current gain beta of a common two-pole transistor is generally below 250. They are referred to as high-beta or high gain transistors when the beta of such transistors exceeds 300. When the beta of a transistor is higher than 1,000, it is called a super-beta transistor (SBT) or supergain transistor. The micropower dissipation type has the widest applications among the high-beta. Micropower dissipation high-beta means that there is a high gain or a superhigh gain under a microcurrent. The device is widely used in small signal-detection systems and stereo audio equipment because of their characteristics of high gain, low frequency and low noise under small signals.

Harnessing the theoretical foundations of the exponential and beta-Poisson dose-response models to quantify parameter uncertainty using Markov Chain Monte Carlo.

PubMed

Schmidt, Philip J; Pintar, Katarina D M; Fazil, Aamir M; Topp, Edward

2013-09-01

Dose-response models are the essential link between exposure assessment and computed risk values in quantitative microbial risk assessment, yet the uncertainty that is inherent to computed risks because the dose-response model parameters are estimated using limited epidemiological data is rarely quantified. Second-order risk characterization approaches incorporating uncertainty in dose-response model parameters can provide more complete information to decisionmakers by separating variability and uncertainty to quantify the uncertainty in computed risks. Therefore, the objective of this work is to develop procedures to sample from posterior distributions describing uncertainty in the parameters of exponential and beta-Poisson dose-response models using Bayes's theorem and Markov Chain Monte Carlo (in OpenBUGS). The theoretical origins of the beta-Poisson dose-response model are used to identify a decomposed version of the model that enables Bayesian analysis without the need to evaluate Kummer confluent hypergeometric functions. Herein, it is also established that the beta distribution in the beta-Poisson dose-response model cannot address variation among individual pathogens, criteria to validate use of the conventional approximation to the beta-Poisson model are proposed, and simple algorithms to evaluate actual beta-Poisson probabilities of infection are investigated. The developed MCMC procedures are applied to analysis of a case study data set, and it is demonstrated that an important region of the posterior distribution of the beta-Poisson dose-response model parameters is attributable to the absence of low-dose data. This region includes beta-Poisson models for which the conventional approximation is especially invalid and in which many beta distributions have an extreme shape with questionable plausibility. © Her Majesty the Queen in Right of Canada 2013. Reproduced with the permission of the Minister of the Public Health Agency of Canada.

75 FR 51823 - Government-Owned Inventions; Availability for Licensing

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-23

... applications. Transforming Growth Factor Beta-1 (TGF-[beta]1) Transgenic Mouse Model Description of Technology... developed a transgenic mouse model, designated [beta]1\\glo\\, which permits conditional, gene-specific... gene by Cre recombinase allows expression of TGF-[beta]1. Thus, these mice may be cross-bred with a...

Periodontal wound healing/regeneration following implantation of recombinant human growth/differentiation factor-5 in a beta-tricalcium phosphate carrier into one-wall intrabony defects in dogs.

PubMed

Lee, Jung-Seok; Wikesjö, Ulf M E; Jung, Ui-Won; Choi, Seong-Ho; Pippig, Susanne; Siedler, Michael; Kim, Chong-Kwan

2010-04-01

Recombinant human growth/differentiation factor-5 (rhGDF-5) is being evaluated as a candidate therapy in support of periodontal regeneration. The objective of this study was to evaluate periodontal wound healing/regeneration following the application of rhGDF-5 on a particulate beta-tricalcium phosphate (beta-TCP) carrier using an established defect model. Bilateral 4 x 5 mm (width x depth), one-wall, critical-size, intrabony periodontal defects were surgically created at the mandibular second and fourth pre-molar teeth in 15 Beagle dogs. Unilateral defects in five animals received rhGDF-5/beta-TCP (Scil Technology GmbH); five animals received beta-TCP solo; and five animals served as sham-surgery controls. Contralateral sites received treatments reported elsewhere. The animals were sacrificed following an 8-week healing interval for histological examination. Clinical healing was generally uneventful. Sites implanted with rhGDF-5/beta-TCP exhibited greater enhanced cementum and bone formation compared with beta-TCP and sham-surgery controls; cementum regeneration averaged (+/- SD) 3.83 +/- 0.73 versus 1.65 +/- 0.82 and 2.48 +/- 1.28 mm for the controls (p<0.05). Corresponding values for bone regeneration height averaged 3.26 +/- 0.30 versus 1.70 +/- 0.66 and 1.68 +/- 0.49 mm (p<0.05), and bone area 10.45 +/- 2.26 versus 6.31 +/- 2.41 and 3.00 +/- 1.97 mm(2) (p<0.05). Cementum regeneration included cellular/acellular cementum with or without a functionally oriented periodontal ligament. A non-specific connective tissue attachment was evident in the sham-surgery control. Controls exhibited mostly woven bone with primary osteons, whereas rhGDF-5/beta-TCP sites showed a noticeable extent of lamellar bone. Sites receiving rhGDF-5/beta-TCP or beta-TCP showed some residual beta-TCP granules apparently undergoing biodegradation without obvious differences between the sites. Sites receiving beta-TCP alone commonly showed residual beta-TCP granules sequestered in the connective tissue or fibrovascular marrow. rhGDF-5/beta-TCP has a greater potential to support the regeneration of the periodontal attachment. Long-term studies are necessary to confirm the uneventful maturation of the regenerated tissues.

High frequency fishbone driven by passing energetic ions in tokamak plasmas

NASA Astrophysics Data System (ADS)

Wang, Feng; Yu, L. M.; Fu, G. Y.; Shen, Wei

2017-05-01

High frequency fishbone instability driven by passing energetic ions was first reported in the Princeton beta experiment with tangential neutral-beam-injection (Heidbrink et al 1986 Phys. Rev. Lett. 57 835-8). It could play an important role for ITER-like burning plasmas, where α particles are mostly passing particles. In this work, a generalized energetic ion distribution function and finite drift orbit width effect are considered to improve the theoretical model for passing particle driving fishbone instability. For purely passing energetic ions with zero drift orbit width, the kinetic energy δ {{W}k} is derived analytically. The derived analytic expression is more accurate as compared to the result of previous work (Wang 2001 Phys. Rev. Lett. 86 5286-8). For a generalized energetic ion distribution function, the fishbone dispersion relation is derived and is solved numerically. Numerical results show that broad and off-axis beam density profiles can significantly increase the beam ion beta threshold {βc} for instability and decrease mode frequency.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Berry, Max; Lystig, Ted; Beard, Jonathan

Purpose. To compare the learning of endovascular interventional skills by training on pig models versus virtual reality simulators. Methods. Twelve endovascular novices participated in a study consisting of a pig laboratory (P-Lab) and a virtual reality laboratory (VR-Lab). Subjects were stratified by experience and randomized into four training groups. Following 1 hr of didactic instruction, all attempted an iliac artery stenosis (IAS) revascularization in both laboratories. Onsite proctors evaluated performances using task-specific checklists and global rating scales, yielding a Total Score. Participants completed two training sessions of 3 hr each, using their group's assigned method (P-Lab x 2, P-Lab +more » VR-Lab, VR-Lab + P-Lab, or VR-Lab x 2) and were re-evaluated in both laboratories. A panel of two highly experienced interventional radiologists performed assessments from video recordings. ANCOVA analysis of Total Score against years of surgical, interventional radiology (IR) experience and cumulative number of P-Lab or VR-Lab sessions was conducted. Inter-rater reliability (IRR) was determined by comparing proctored scores with the video assessors in only the VR-Lab. Results. VR-Lab sessions improved the VR-Lab Total Score ({beta} 3.029, p = 0.0015) and P-Lab Total Score ({beta} = 1.814, p = 0.0452). P-Lab sessions increased the P-Lab Total Score ({beta} = 4.074, p < 0.0001) but had no effect on the VR-Lab Total Score. In the general statistical model, both P-Lab sessions ({beta} = 2.552, p = 0.0010) and VR-Lab sessions ({beta} 2.435, p = 0.0032) significantly improved Total Score. Neither previous surgical experience nor IR experience predicted Total Score. VR-Lab scores were consistently higher than the P-Lab scores ({delta} = 6.659, p < 0.0001). VR-Lab IRR was substantial (r = 0.649, p < 0.0008). Conclusions. Endovascular skills learned in the virtual environment may be transferable to the real catheterization laboratory as modeled in the P-Lab.« less

Partitioning diversity into independent alpha and beta components.

PubMed

Jost, Lou

2007-10-01

Existing general definitions of beta diversity often produce a beta with a hidden dependence on alpha. Such a beta cannot be used to compare regions that differ in alpha diversity. To avoid misinterpretation, existing definitions of alpha and beta must be replaced by a definition that partitions diversity into independent alpha and beta components. Such a unique definition is derived here. When these new alpha and beta components are transformed into their numbers equivalents (effective numbers of elements), Whittaker's multiplicative law (alpha x beta = gamma) is necessarily true for all indices. The new beta gives the effective number of distinct communities. The most popular similarity and overlap measures of ecology (Jaccard, Sorensen, Horn, and Morisita-Horn indices) are monotonic transformations of the new beta diversity. Shannon measures follow deductively from this formalism and do not need to be borrowed from information theory; they are shown to be the only standard diversity measures which can be decomposed into meaningful independent alpha and beta components when community weights are unequal.

Impaired activation of adenylyl cyclase in lung of the Basenji-greyhound model of airway hyperresponsiveness: decreased numbers of high affinity beta-adrenoceptors.

PubMed Central

Emala, C. W.; Aryana, A.; Hirshman, C. A.

1996-01-01

1. To evaluate mechanisms involved in the impaired beta-adrenoceptor stimulation of adenylyl cyclase in tissues from the Basenji-greyhound (BG) dog model of airway hyperresponsiveness, we compared agonist and antagonist binding affinity of beta-adrenoceptors, beta-adrenoceptor subtypes, percentage of beta-adrenoceptors sequestered, and coupling of the beta-adrenoceptor to Gs alpha in lung membranes from BG and control mongrel dogs. We found that lung membranes from the BG dog had higher total numbers of beta-adrenoceptors with a greater percentage of receptors of the beta 2 subtype as compared to mongrel lung membranes. 2. Agonist and antagonist binding affinity and the percentage of beta-adrenoceptors sequestered were not different in BG and mongrel dog lung membranes. However, the percentage of beta-adrenoceptors in the high affinity state for agonist was decreased in BG lung membranes suggesting an uncoupling of the receptor from Gs alpha. 3. Impaired coupling between the beta-adrenoceptor and G protein documented by the decreased numbers of beta-adrenoceptors in the high affinity state in BG lung membranes, is a plausible explanation for the reduced stimulation of adenylyl cyclase and the resultant reduction in airway smooth muscle relaxation in this model. PMID:8864536

Association of GSK3beta polymorphisms with brain structural changes in major depressive disorder.

PubMed

Inkster, Becky; Nichols, Thomas E; Saemann, Philipp G; Auer, Dorothee P; Holsboer, Florian; Muglia, Pierandrea; Matthews, Paul M

2009-07-01

Indirect evidence suggests that the glycogen synthase kinase-3beta (GSK3beta) gene might be implicated in major depressive disorder (MDD). We evaluated 15 GSK3beta single-nucleotide polymorphisms (SNPs) to test for associations with regional gray matter (GM) volume differences in patients with recurrent MDD. We then used the defined regions of interest based on significant associations to test for MDD x genotype interactions by including a matched control group without any psychiatric disorder, including MDD. General linear model with nonstationary cluster-based inference. Munich, Germany. Patients with recurrent MDD (n = 134) and age-, sex-, and ethnicity-matched healthy controls (n = 143). Associations between GSK3beta polymorphisms and regional GM volume differences. Variation in GM volume was associated with GSK3beta polymorphisms; the most significant associations were found for rs6438552, a putative functional intronic SNP that showed 3 significant GM clusters in the right and left superior temporal gyri and the right hippocampus (P < .001, P = .02, and P = .02, respectively, corrected for multiple comparisons across the whole brain). Similar results were obtained with rs12630592, an SNP in high linkage disequilibrium. A significant SNP x MDD status interaction was observed for the effect on GM volumes in the right hippocampus and superior temporal gyri (P < .001 and P = .01, corrected, respectively). The GSK3beta gene may have a role in determining regional GM volume differences of the right hippocampus and bilateral superior temporal gyri. The association between genotype and brain structure was specific to the patients with MDD, suggesting that GSK3beta genotypes might interact with MDD status. We speculate that this is a consequence of regional neocortical, glial, or neuronal growth or survival. In considering core cognitive features of MDD, the association of GSK3beta polymorphisms with structural variation in the temporal lobe and hippocampus is of particular interest in the context of other evidence for structural and functional abnormalities in the hippocampi of patients with MDD.

Interleukin-1 may link helplessness-hopelessness with cancer progression: a proposed model.

PubMed

Argaman, Miriam; Gidron, Yori; Ariad, Shmuel

2005-01-01

A model of the relations between psychological factors and cancer progression should include brain and systemic components and their link with critical cellular stages in cancer progression. We present a psychoneuroimmunological (PNI) model that links helplessness-hopelessness (HH) with cancer progression via interleukin-1beta (IL-1beta). IL-1beta was elevated in the brain following exposure to inescapable shock, and HH was minimized by antagonizing cerebral IL-1beta. Elevated cerebral IL-1beta increased cancer metastasis in animals. Inescapable shock was associated with systemic elevations of IL-1beta and peripheral IL-1beta was associated with escape from apoptosis, angiogenesis, and metastasis. Involvement of the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis are discussed. Future studies need to identify the role of additional factors in this PNI pathway.

Comparison of GEANT4 Physics Models with Measured Beta Particle Data in Aluminum using a Strontium-90 Source

NASA Astrophysics Data System (ADS)

Everett, Samantha

2010-10-01

A transmission curve experiment was carried out to measure the range of beta particles in aluminum in the health physics laboratory located on the campus of Texas Southern University. The transmission count rate through aluminum for varying radiation lengths was measured using beta particles emitted from a low activity (˜1 μCi) Sr-90 source. The count rate intensity was recorded using a Geiger Mueller tube (SGC N210/BNC) with an active volume of 61 cm^3 within a systematic detection accuracy of a few percent. We compared these data with a realistic simulation of the experimental setup using the Geant4 Monte Carlo toolkit (version 9.3). The purpose of this study was to benchmark our Monte Carlo for future experiments as part of a more comprehensive research program. Transmission curves were simulated based on the standard and low-energy electromagnetic physics models, and using the radioactive decay module for the electrons primary energy distribution. To ensure the validity of our measurements, linear extrapolation techniques were employed to determine the in-medium beta particle range from the measured data and was found to be 1.87 g/cm^2 (˜0.693 cm), in agreement with literature values. We found that the general shape of the measured data and simulated curves were comparable; however, a discrepancy in the relative count rates was observed. The origin of this disagreement is still under investigation.

Explaining variation in tropical plant community composition: influence of environmental and spatial data quality.

PubMed

Jones, Mirkka M; Tuomisto, Hanna; Borcard, Daniel; Legendre, Pierre; Clark, David B; Olivas, Paulo C

2008-03-01

The degree to which variation in plant community composition (beta-diversity) is predictable from environmental variation, relative to other spatial processes, is of considerable current interest. We addressed this question in Costa Rican rain forest pteridophytes (1,045 plots, 127 species). We also tested the effect of data quality on the results, which has largely been overlooked in earlier studies. To do so, we compared two alternative spatial models [polynomial vs. principal coordinates of neighbour matrices (PCNM)] and ten alternative environmental models (all available environmental variables vs. four subsets, and including their polynomials vs. not). Of the environmental data types, soil chemistry contributed most to explaining pteridophyte community variation, followed in decreasing order of contribution by topography, soil type and forest structure. Environmentally explained variation increased moderately when polynomials of the environmental variables were included. Spatially explained variation increased substantially when the multi-scale PCNM spatial model was used instead of the traditional, broad-scale polynomial spatial model. The best model combination (PCNM spatial model and full environmental model including polynomials) explained 32% of pteridophyte community variation, after correcting for the number of sampling sites and explanatory variables. Overall evidence for environmental control of beta-diversity was strong, and the main floristic gradients detected were correlated with environmental variation at all scales encompassed by the study (c. 100-2,000 m). Depending on model choice, however, total explained variation differed more than fourfold, and the apparent relative importance of space and environment could be reversed. Therefore, we advocate a broader recognition of the impacts that data quality has on analysis results. A general understanding of the relative contributions of spatial and environmental processes to species distributions and beta-diversity requires that methodological artefacts are separated from real ecological differences.

Lovastatin inhibits amyloid precursor protein (APP) beta-cleavage through reduction of APP distribution in Lubrol WX extractable low density lipid rafts.

PubMed

Won, Je-Seong; Im, Yeong-Bin; Khan, Mushfiquddin; Contreras, Miguel; Singh, Avtar K; Singh, Inderjit

2008-05-01

Previous studies have described that statins (inhibitors of cholesterol and isoprenoid biosynthesis) inhibit the output of amyloid-beta (Abeta) in the animal model and thus decrease risk of Alzheimer's disease. However, their action mechanism(s) in Abeta precursor protein (APP) processing and Abeta generation is not fully understood. In this study, we report that lovastatin treatment reduced Abeta output in cultured hippocampal neurons as a result of reduced APP levels and beta-secretase activities in low density Lubrol WX (non-ionic detergent) extractable lipid rafts (LDLR). Rather than altering cholesterol levels in lipid raft fractions and thus disrupting lipid raft structure, lovastatin decreased Abeta generation through down-regulating geranylgeranyl-pyrophosphate dependent endocytosis pathway. The inhibition of APP endocytosis by treatment with lovastatin and reduction of APP levels in LDLR fractions by treatment with phenylarsine oxide (a general endocytosis inhibitor) support the involvement of APP endocytosis in APP distribution in LDLR fractions and subsequent APP beta-cleavage. Moreover, lovastatin-mediated down-regulation of endocytosis regulators, such as early endosomal antigen 1, dynamin-1, and phosphatidylinositol 3-kinase activity, indicates that lovastatin modulates APP endocytosis possibly through its pleiotropic effects on endocytic regulators. Collectively, these data report that lovastatin mediates inhibition of LDLR distribution and beta-cleavage of APP in a geranylgeranyl-pyrophosphate and endocytosis-dependent manner.

Dynamics of beta-amyloid peptide in cholesterol superlattice domain

NASA Astrophysics Data System (ADS)

Smirnov, Anton; Zhu, Qing; Vaughn, Mark; Khare, Rajesh; Cheng, K.

2006-10-01

Presence of beta-amyloid peptide (beta-A) plagues in membranes of neuron cells is a clinical signature of Alzheimer disease. The onset of beta-A peptide aggregation occurs via a conformational transition from an alpha-helix state to a beta-sheet state. A gradual build-up of beta-A content in the neuronal extracellular space is another characteristic of the beta-A plague formation. Hypothetically, both the pathological conformation and the predominant localization of the beta-A can be a result of specific dynamic characteristics of the interphase between cellular membrane and extracellular milieu. In this study, the beta-A interphase problem has been investigated using a virtual membrane model implemented on the base of GROMACS molecular dynamics simulation package. The detailed folding pattern of beta-A has been examined using a novice interphase model comprised of a cholesterol supperlattice membrane and two water layers.

Gross-beta activity in ground water: natural sources and artifacts of sampling and laboratory analysis

USGS Publications Warehouse

Welch, Alan H.

1995-01-01

Gross-beta activity has been used as an indicator of beta-emitting isotopes in water since at least the early 1950s. Originally designed for detection of radioactive releases from nuclear facilities and weapons tests, analysis of gross-beta activity is widely used in studies of naturally occurring radioactivity in ground water. Analyses of about 800 samples from 5 ground-water regions of the United States provide a basis for evaluating the utility of this measurement. The data suggest that measured gross-beta activities are due to (1) long-lived radionuclides in ground water, and (2) ingrowth of beta-emitting radionuclides during holding times between collection of samples and laboratory measurements.Although40K and228Ra appear to be the primary sources of beta activity in ground water, the sum of40K plus228Ra appears to be less than the measured gross-beta activity in most ground-water samples. The difference between the contribution from these radionuclides and gross-beta activity is most pronounced in ground water with gross-beta activities > 10 pCi/L, where these 2 radionuclides account for less than one-half the measured ross-beta activity. One exception is groundwater from the Coastal Plain of New Jersey, where40K plus228Ra generally contribute most of the gross-beta activity. In contrast,40K and228Ra generally contribute most of beta activity in ground water with gross-beta activities < 1 pCi/L.The gross-beta technique does not measure all beta activity in ground water. Although3H contributes beta activity to some ground water, it is driven from the sample before counting and therefore is not detected by gross-beta measurements. Beta-emitting radionuclides with half-lives shorter than a few days can decay to low values between sampling and counting. Although little is known about concentrations of most short-lived beta-emitting radionuclides in environmental ground water (water unaffected by direct releases from nuclear facilities and weapons tests), their activities are expected to be low.Ingrowth of beta-emitting radionuclides during sample holding times can contribute to gross-beta activity, particularly in ground water with gross-beta activities > 10 pCi/L. Ingrowth of beta-emitting progeny of238U, specifically234Pa and234Th, contributes much of the measured gross-beta activity in ground water from 4 of the 5 areas studied. Consequently, gross-beta activity measurements commonly overestimate the abundance of beta-emitting radionuclides actually present in ground water. Differing sample holding times before analysis lead to differing amounts of ingrowth of the two progeny. Therefore, holding times can affect observed gross-beta measurements, particularly in ground water with238U activities that are moderate to high compared with the activity of40K plus228Ra. Uncertainties associated with counting efficiencies for beta particles with different energies further complicate the interpretation of gross-beta measurements.

Proteomic analysis of B-aminobutyric acid priming and aba-induction of drought resistance in crabapple (Malus pumila): effect on general metabolism, the phenylpropanoid pathway and cell wall enzymes

USDA-ARS?s Scientific Manuscript database

In a variety of annual crops and model plants, the xenobiotic compound, DL-beta-aminobutyric acid (BABA), has been shown to enhance disease resistance and increase salt, drought, and thermotolerance. BABA does not activate stress genes directly but rather sensitizes plants to respond more quickly a...

Association of T-cell reactivity with beta-cell function in recent onset type 1 diabetes patients.

PubMed

Pfleger, Christian; Meierhoff, Guido; Kolb, Hubert; Schloot, Nanette C

2010-03-01

The aim of the current study was to investigate whether autoantigen directed T-cell reactivity relates to beta-cell function during the first 78 weeks after diagnosis of type 1 diabetes. 50 adults and 49 children (mean age 27.3 and 10.9 years respectively) with recent onset type 1 diabetes who participated in a placebo-controlled trial of immune intervention with DiaPep277 were analyzed. Secretion of interferon (IFN)-gamma, interleukin (IL)-5, IL-13 and IL-10 by single peripheral mononuclear cells (PBMC) upon stimulation with islet antigens GAD65, heat shock protein 60 (Hsp60) protein-tyrosine-phosphatase-like-antigen (pIA2) or tetanus toxoid (TT) was determined applying ELISPOT; beta-cell function was evaluated by glucagon stimulated C-peptide. Multivariate regression analysis was applied. In general, number of islet antigen-reactive cells decreased over 78 weeks in both adults and children, whereas reactivity to TT was not reduced. In addition, there was an association between the quality of immune cell responses and beta-cell function. Overall, increased responses by IFN-gamma secreting cells were associated with lower beta-cell function whereas IL-5, IL-13 and IL-10 cytokine responses were positively associated with beta-cell function in adults and children. Essentially, the same results were obtained with three different models of regression analysis. The number of detectable islet-reactive immune cells decreases within 1-2 years after diagnosis of type 1 diabetes. Cytokine production by antigen-specific PBMC reactivity is related to beta-cell function as measured by stimulated C-peptide. Cellular immunity appears to regress soon after disease diagnosis and begin of insulin therapy. Copyright 2009 Elsevier Ltd. All rights reserved.

Observations on the deformation-induced beta internal friction peak in bcc metals

NASA Technical Reports Server (NTRS)

Dicarlo, J. A.

1974-01-01

During a study of the effects of electron irradiation on the tungsten alpha mechanism, internal friction data were obtained. The data indicate that the mechanism underlying the beta peak does not possess the relaxation parameters generally associated with a simple dislocation process. The significance of the experimental results in the light of beta observations in other metals is discussed. It is suggested that the beta peaks in deformed bcc metals are the anelastic result of the thermally-activated relaxation of deformation-induced imperfections.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Takata, Takumi; Shimo-Oka, Tadashi; Kojima, Masami

Although proteins are generally composed of L-{alpha}-amino acids, D-{beta}-aspartic acid (Asp)-containing proteins have been reported in various elderly tissues. Our previous study detected several D-{beta}-Asp-containing proteins in a rabbit lens derived from epithelial cell line by Western blot analysis of a 2D-gel using a polyclonal antibody that is highly specific for D-{beta}-Asp-containing proteins. The identity of each spot was subsequently determined by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and the Ms-Fit online database searching algorithm. In this study, we discovered novel D-{beta}-Asp-containing proteins from rabbit lens. The results indicate that {beta}-crystallin A3, {beta}-crystallin A4, {beta}-crystallin B1, {beta}-crystallin B2, {beta}-crystallin B3,more » {gamma}-crystallin C, {gamma}-crystallin D, and {lambda}-crystallin in rabbit lens contain D-{beta}-Asp residues. Furthermore, the occurrence of D-{beta}-Asp residues increases with infrared ray (IR) irradiation. Additionally, some D-{beta}-Asp-containing proteins only appear after IR irradiation. One such protein is the {alpha}-enolase, which shows homology to {tau}-crystallin.« less

The prospective relationship between satisfaction with information and symptoms of depression and anxiety in breast cancer: A structural equation modeling analysis.

PubMed

Faller, Hermann; Strahl, André; Richard, Matthias; Niehues, Christiane; Meng, Karin

2017-11-01

Previous research has demonstrated associations between satisfaction with information and reduced emotional distress in cancer patients. However, as most studies were cross-sectional, the direction of this relationship remained unclear. We therefore aimed to test whether information satisfaction predicted subsequent depression and anxiety levels, and, reciprocally, depression and anxiety levels predicted subsequent information satisfaction, thus clarifying the direction of impact. We performed a secondary analysis of a prospective cohort study with 436 female breast cancer patients (mean age 51 years). We measured information satisfaction with 2 self-developed items, symptoms of depression with the 2-item Patient Heath Questionnaire and symptoms of anxiety with the 2-item Generalized Anxiety Disorder Scale. We created 2 structural equation models, 1 for depression and 1 for anxiety, that examined the prediction of 1-year depression (or anxiety) levels by baseline information satisfaction and, in the same model, 1-year information satisfaction by baseline depression (or anxiety) levels (cross-lagged panel analysis). Baseline information satisfaction predicted 1-year levels of both depression (beta = -0.17, P < .01) and anxiety (beta = -0.13, P < .01), adjusting for the baseline scores of the outcome variables. Conversely, baseline levels of depression (beta = -0.12, P < .05) and anxiety (beta = -0.16, P < .01) predicted 1-year information satisfaction, adjusting for its baseline score. Our results suggest a bidirectional relationship between information satisfaction and symptoms of depression and anxiety. Thus, provision of information may reduce subsequent depression and anxiety, while reducing depression and anxiety levels may increase satisfaction with received information. Combining the provision of information with emotional support may be particularly beneficial. Copyright © 2016 John Wiley & Sons, Ltd.

Beta-catenin is required for memory consolidation.

PubMed

Maguschak, Kimberly A; Ressler, Kerry J

2008-11-01

beta-catenin has been implicated in neuronal synapse regulation and remodeling. Here we have examined beta-catenin expression in the adult mouse brain and its role in amygdala-dependent learning and memory. We found alterations in beta-catenin mRNA and protein phosphorylation during fear-memory consolidation. Such alterations correlated with a change in the association of beta-catenin with cadherin. Pharmacologically, this consolidation was enhanced by lithium-mediated facilitation of beta-catenin. Genetically, the role of beta-catenin was confirmed with site-specific deletions of loxP-flanked Ctnnb1 (encoding beta-catenin) in the amygdala. Baseline locomotion, anxiety-related behaviors and acquisition or expression of conditioned fear were normal. However, amygdala-specific deletion of Ctnnb1 prevented the normal transfer of newly formed fear learning into long-term memory. Thus, beta-catenin may be required in the amygdala for the normal consolidation, but not acquisition, of fear memory. This suggests a general role for beta-catenin in the synaptic remodeling and stabilization underlying long-term memory in adults.

Generalized one-loop neutrino mass model with charged particles

NASA Astrophysics Data System (ADS)

Cheung, Kingman; Okada, Hiroshi

2018-04-01

We propose a radiative neutrino-mass model by introducing 3 generations of fermion pairs E-(N +1 )/2E+(N +1 )/2 and a couple of multicharged bosonic doublet fields ΦN /2,ΦN /2 +1, where N =1 , 3, 5, 7, 9. We show that the models can satisfy the neutrino masses and oscillation data, and are consistent with lepton-flavor violations, the muon anomalous magnetic moment, the oblique parameters, and the beta function of the U (1 )Y hypercharge gauge coupling. We also discuss the collider signals for various N , namely, multicharged leptons in the final state from the Drell-Yan production of E-(N +1 )/2E+(N +1 )/2. In general, the larger the N the more charged leptons will appear in the final state.

Increasing protein stability by improving beta-turns.

PubMed

Fu, Hailong; Grimsley, Gerald R; Razvi, Abbas; Scholtz, J Martin; Pace, C Nick

2009-11-15

Our goal was to gain a better understanding of how protein stability can be increased by improving beta-turns. We studied 22 beta-turns in nine proteins with 66-370 residues by replacing other residues with proline and glycine and measuring the stability. These two residues are statistically preferred in some beta-turn positions. We studied: Cold shock protein B (CspB), Histidine-containing phosphocarrier protein, Ubiquitin, Ribonucleases Sa2, Sa3, T1, and HI, Tryptophan synthetase alpha-subunit, and Maltose binding protein. Of the 15 single proline mutations, 11 increased stability (Average = 0.8 +/- 0.3; Range = 0.3-1.5 kcal/mol), and the stabilizing effect of double proline mutants was additive. On the basis of this and our previous work, we conclude that proteins can generally be stabilized by replacing nonproline residues with proline residues at the i + 1 position of Type I and II beta-turns and at the i position in Type II beta-turns. Other turn positions can sometimes be used if the phi angle is near -60 degrees for the residue replaced. It is important that the side chain of the residue replaced is less than 50% buried. Identical substitutions in beta-turns in related proteins give similar results. Proline substitutions increase stability mainly by decreasing the entropy of the denatured state. In contrast, the large, diverse group of proteins considered here had almost no residues in beta-turns that could be replaced by Gly to increase protein stability. Improving beta-turns by substituting Pro residues is a generally useful way of increasing protein stability. 2009 Wiley-Liss, Inc.

A predictive model of Health Related Quality of life of parents of chronically ill children: the importance of care-dependency of their child and their support system.

PubMed

Hatzmann, Janneke; Maurice-Stam, Heleen; Heymans, Hugo S A; Grootenhuis, Martha A

2009-07-28

Parents of chronically ill children are at risk for a lower Health Related Quality of Life (HRQoL). Insight in the dynamics of factors influencing parental HRQoL is necessary for development of interventions. Aim of the present study was to explore the influence of demographic and disease related factors on parental HRQoL, mediated by employment, income, leisure time, holiday and emotional support in a comprehensive model. In a cross-sectional design, 543 parents of chronically ill children completed questionnaires. A conceptual model of parental HRQoL was developed. Structural equation modeling was performed to explore the relations in the conceptual model, and to test if the model fitted the data. The model fitted the data closely (CHISQ(14) = 11.37, p = 0.66; RMSEA = 0.0, 90%CI [0.00;0.034]. The effect of socio-demographic and medical data on HRQoL was mediated by days on holiday (MCS: beta = .21) and emotional support (PCS: beta = .14; MCS: beta = .28). Also, female gender (beta = -.10), age (beta = .10), being chronically ill as a parent (beta = -.34), and care dependency of the child (beta = -.14; beta = -.15) were directly related to parental HRQoL. The final model was slightly different from the conceptual model. Main factors explaining parental HRQoL seemed to be emotional support, care dependency, days on holiday and being chronically ill as a parent. Holiday and emotional support mediated the effect of demographic and disease-related factors on HRQoL. Hours of employment, leisure time and household income did not mediate between background characteristics and HRQoL, contrasting the hypotheses.

Global mammal beta diversity shows parallel assemblage structure in similar but isolated environments

PubMed Central

Graham, Catherine H.; Brooks, Thomas M.; Rondinini, Carlo; Hedges, S. Blair; Davidson, Ana D.; Costa, Gabriel C.

2016-01-01

The taxonomic, phylogenetic and trait dimensions of beta diversity each provide us unique insights into the importance of historical isolation and environmental conditions in shaping global diversity. These three dimensions should, in general, be positively correlated. However, if similar environmental conditions filter species with similar trait values, then assemblages located in similar environmental conditions, but separated by large dispersal barriers, may show high taxonomic, high phylogenetic, but low trait beta diversity. Conversely, we expect lower phylogenetic diversity, but higher trait biodiversity among assemblages that are connected but are in differing environmental conditions. We calculated all pairwise comparisons of approximately 110 × 110 km grid cells across the globe for more than 5000 mammal species (approx. 70 million comparisons). We considered realms as units representing geographical distance and historical isolation and biomes as units with similar environmental conditions. While beta diversity dimensions were generally correlated, we highlight geographical regions of decoupling among beta diversity dimensions. Our analysis shows that assemblages from tropical forests in different realms had low trait dissimilarity while phylogenetic beta diversity was significantly higher than expected, suggesting potential convergent evolution. Low trait beta diversity was surprisingly not found between isolated deserts, despite harsh environmental conditions. Overall, our results provide evidence for parallel assemblage structure of mammal assemblages driven by environmental conditions at a global scale. PMID:27559061

Chemical cross-linking of the urease complex from Helicobacter pylori and analysis by Fourier transform ion cyclotron resonance mass spectrometry and molecular modeling

NASA Astrophysics Data System (ADS)

Carlsohn, Elisabet; Ångström, Jonas; Emmett, Mark R.; Marshall, Alan G.; Nilsson, Carol L.

2004-05-01

Chemical cross-linking of proteins is a well-established method for structural mapping of small protein complexes. When combined with mass spectrometry, cross-linking can reveal protein topology and identify contact sites between the peptide surfaces. When applied to surface-exposed proteins from pathogenic organisms, the method can reveal structural details that are useful in vaccine design. In order to investigate the possibilities of applying cross-linking on larger protein complexes, we selected the urease enzyme from Helicobacter pylori as a model. This membrane-associated protein complex consists of two subunits: [alpha] (26.5 kDa) and [beta] (61.7 kDa). Three ([alpha][beta]) heterodimers form a trimeric ([alpha][beta])3 assembly which further associates into a unique dodecameric 1.1 MDa complex composed of four ([alpha][beta])3 units. Cross-linked peptides from trypsin-digested urease complex were analyzed by Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) and molecular modeling. Two potential cross-linked peptides (present in the cross-linked sample but undetectable in [alpha], [beta], and native complex) were assigned. Molecular modeling of urease [alpha][beta] complex and trimeric urease units ([alpha][beta])3 revealed a linkage site between the [alpha]-subunit and the [beta]-subunit, and an internal cross-linkage in the [beta]-subunit.

Exact Scheffé-type confidence intervals for output from groundwater flow models: 1. Use of hydrogeologic information

USGS Publications Warehouse

Cooley, Richard L.

1993-01-01

A new method is developed to efficiently compute exact Scheffé-type confidence intervals for output (or other function of parameters) g(β) derived from a groundwater flow model. The method is general in that parameter uncertainty can be specified by any statistical distribution having a log probability density function (log pdf) that can be expanded in a Taylor series. However, for this study parameter uncertainty is specified by a statistical multivariate beta distribution that incorporates hydrogeologic information in the form of the investigator's best estimates of parameters and a grouping of random variables representing possible parameter values so that each group is defined by maximum and minimum bounds and an ordering according to increasing value. The new method forms the confidence intervals from maximum and minimum limits of g(β) on a contour of a linear combination of (1) the quadratic form for the parameters used by Cooley and Vecchia (1987) and (2) the log pdf for the multivariate beta distribution. Three example problems are used to compare characteristics of the confidence intervals for hydraulic head obtained using different weights for the linear combination. Different weights generally produced similar confidence intervals, whereas the method of Cooley and Vecchia (1987) often produced much larger confidence intervals.

Diversity time-period and diversity-time-area relationships exemplified by the human microbiome.

PubMed

Ma, Zhanshan Sam

2018-05-08

We extend the ecological laws of species-time relationship (STR) and species-time-area relationship (STAR) to general diversity time-period relationship (DTR) and diversity-time-area relationship (DTAR), and test the extensions with the human vaginal microbiome datasets by building 1460 DTR/DTAR models. Our extensions were inspired by the observation that Hill numbers, well regarded as the most appropriate measure of alpha-diversity and also particularly suitable for multiplicative beta-diversity partitioning, are actually in the units of effective species, and therefore, should be able to substitute for species in the STR and STAR. We found that the traditional power law (PL) model is only applicable for DTR at diversity order zero (i.e., species richness); at higher diversity orders (q = 1-4), the power law with exponent cutoff (PLEC) and power law with inverse exponent cutoff (PLIEC) are more appropriate. In particular, PLEC has an advantage over PLIEC in predicting maximal accumulation diversity (MAD) over time. In fact, with the DTR extensions, we can construct DTR and MAD profiles. To the best of our knowledge, this is the first comprehensive investigation of the DTR/DTAR in human microbiome. Methodologically, our DTR/DTAR profiles can characterize general diversity scaling beyond species richness, covering both alpha- and beta-diversity regimes across different diversity orders.

Rapid model building of beta-sheets in electron-density maps.

PubMed

Terwilliger, Thomas C

2010-03-01

A method for rapidly building beta-sheets into electron-density maps is presented. beta-Strands are identified as tubes of high density adjacent to and nearly parallel to other tubes of density. The alignment and direction of each strand are identified from the pattern of high density corresponding to carbonyl and C(beta) atoms along the strand averaged over all repeats present in the strand. The beta-strands obtained are then assembled into a single atomic model of the beta-sheet regions. The method was tested on a set of 42 experimental electron-density maps at resolutions ranging from 1.5 to 3.8 A. The beta-sheet regions were nearly completely built in all but two cases, the exceptions being one structure at 2.5 A resolution in which a third of the residues in beta-sheets were built and a structure at 3.8 A in which under 10% were built. The overall average r.m.s.d. of main-chain atoms in the residues built using this method compared with refined models of the structures was 1.5 A.

Inhibiting platelet-derived growth factor beta reduces Ewing's sarcoma growth and metastasis in a novel orthotopic human xenograft model.

PubMed

Wang, Yong Xin; Mandal, Deendayal; Wang, Suizhau; Hughes, Dennis; Pollock, Raphael E; Lev, Dina; Kleinerman, Eugenie; Hayes-Jordan, Andrea

2009-01-01

Despite aggressive therapy, Ewing's sarcoma (ES) patients have a poor five-year overall survival of only 20-40%. Pulmonary metastasis is the most common form of demise in these patients. The pathogenesis of pulmonary metastasis is poorly understood and few orthotopic models exist that allow study of spontaneous pulmonary metastasis in ES. We have developed a novel orthotopic xenograft model in which spontaneous pulmonary metastases develop. While the underlying biology of ES is incompletely understood, in addition to the EWS-FLI-1 mutation, it is known that platelet-derived growth factor receptor beta (PDGFR-beta) is highly expressed in ES. Hypothesizing that PDGFR-beta expression is indicative of a specific role for this receptor protein in ES progression, the effect of PDGFR-beta inhibition on ES growth and metastasis was assessed in this novel orthotopic ES model. Silencing PDGFR-beta reduced spontaneous growth and metastasis in ES. Preclinical therapeutically relevant findings such as these may ultimately lead to new treatment initiatives in ES.

Formation of [b3 - 1 + cat]+ ions from metal-cationized tetrapeptides containing beta-alanine, gamma-aminobutyric acid or epsilon-aminocaproic acid residues.

PubMed

Osburn, Sandra M; Ochola, Sila O; Talaty, Erach R; Van Stipdonk, Michael J

2008-11-01

The presence and position of a single beta-alanine (betaA), gamma-aminobutyric acid (gammaABu) or epsilon-aminocaproic acid (Cap) residue has been shown to have a significant influence on the formation of b(n)+ and y(n)+ product ions from a series of model, protonated peptides. In this study, we examined the effect of the same residues on the formation of analogous [b3 - 1 + cat]+ products from metal (Li+, Na+ and Ag+)-cationized peptides. The larger amino acids suppress formation of b3+ from protonated peptides with general sequence AAXG (where X = beta-alanine, gamma-aminobutyric acid or epsilon-aminocaproic acid), presumably because of the prohibitive effect of larger cyclic intermediates in the 'oxazolone' pathway. However, abundant [b3 - 1 + cat]+ products are generated from metal-cationized versions of AAXG. Using a group of deuterium-labeled and exchanged peptides, we found that formation of [b3 - 1 + cat]+ involves transfer of either amide or alpha-carbon position H atoms, and the tendency to transfer the atom from the alpha-carbon position increases with the size of the amino acid in position X. To account for the transfer of the H atom, a mechanism involving formation of a ketene product as [b3 - 1 + cat]+ is proposed.

Statistical thermodynamics of a two-dimensional relativistic gas.

PubMed

Montakhab, Afshin; Ghodrat, Malihe; Barati, Mahmood

2009-03-01

In this paper we study a fully relativistic model of a two-dimensional hard-disk gas. This model avoids the general problems associated with relativistic particle collisions and is therefore an ideal system to study relativistic effects in statistical thermodynamics. We study this model using molecular-dynamics simulation, concentrating on the velocity distribution functions. We obtain results for x and y components of velocity in the rest frame (Gamma) as well as the moving frame (Gamma;{'}) . Our results confirm that Jüttner distribution is the correct generalization of Maxwell-Boltzmann distribution. We obtain the same "temperature" parameter beta for both frames consistent with a recent study of a limited one-dimensional model. We also address the controversial topic of temperature transformation. We show that while local thermal equilibrium holds in the moving frame, relying on statistical methods such as distribution functions or equipartition theorem are ultimately inconclusive in deciding on a correct temperature transformation law (if any).

Pituitary resistance to thyroid hormone associated with a base mutation in the hormone-binding domain of the human 3,5,3'-triiodothyronine receptor-beta.

PubMed

Sasaki, S; Nakamura, H; Tagami, T; Miyoshi, Y; Nogimori, T; Mitsuma, T; Imura, H

1993-05-01

Point mutations in the human T3 receptor-beta (TR beta) gene causing single amino acid substitutions have been identified in several different kindreds with generalized resistance to thyroid hormone. Until now, no study has been reported on the TR gene in cases of pituitary resistance (PRTH). In the present study, we analyzed the TR beta gene in a 30-yr-old Japanese female with PRTH. She exhibited clinical features of hyperthyroidism, elevated serum thyroid hormone levels accompanied by inappropriately increased secretion of TSH, mildly elevated basal metabolic rate, and increased urinary excretion of hydroxyproline. No pituitary tumor was detected. DNA fragments of exons 3-8 of the genomic TR beta gene were generated by the polymerase chain reaction and analyzed by a single stranded conformation polymorphism method. Exon 7 of the patient's TR beta gene showed an abnormal band, suggesting the existence of mutation(s). By subcloning and sequencing the DNA, a point mutation was identified in one allele at nucleotide 1297 (C to T), which altered the 333rd amino acid, arginine, to tryptophan. Neither of her apparently normal parents had any mutations of the TR beta gene. In vitro translation products of the mutant TR beta gene showed remarkably decreased T3-binding activity (Ka, 2.1 x 10(8) M-1; normal TR beta Ka, 1.1 x 10(10) M-1). Since the molecular defect detected in a patient with PRTH is similar to that seen in subjects with generalized resistance to thyroid hormone, both types of the syndrome may represent a continuous spectrum of the same etiological defect with variable tissue resistance to thyroid hormone.

Generalized species sampling priors with latent Beta reinforcements

PubMed Central

Airoldi, Edoardo M.; Costa, Thiago; Bassetti, Federico; Leisen, Fabrizio; Guindani, Michele

2014-01-01

Many popular Bayesian nonparametric priors can be characterized in terms of exchangeable species sampling sequences. However, in some applications, exchangeability may not be appropriate. We introduce a novel and probabilistically coherent family of non-exchangeable species sampling sequences characterized by a tractable predictive probability function with weights driven by a sequence of independent Beta random variables. We compare their theoretical clustering properties with those of the Dirichlet Process and the two parameters Poisson-Dirichlet process. The proposed construction provides a complete characterization of the joint process, differently from existing work. We then propose the use of such process as prior distribution in a hierarchical Bayes modeling framework, and we describe a Markov Chain Monte Carlo sampler for posterior inference. We evaluate the performance of the prior and the robustness of the resulting inference in a simulation study, providing a comparison with popular Dirichlet Processes mixtures and Hidden Markov Models. Finally, we develop an application to the detection of chromosomal aberrations in breast cancer by leveraging array CGH data. PMID:25870462

Robust inference under the beta regression model with application to health care studies.

PubMed

Ghosh, Abhik

2017-01-01

Data on rates, percentages, or proportions arise frequently in many different applied disciplines like medical biology, health care, psychology, and several others. In this paper, we develop a robust inference procedure for the beta regression model, which is used to describe such response variables taking values in (0, 1) through some related explanatory variables. In relation to the beta regression model, the issue of robustness has been largely ignored in the literature so far. The existing maximum likelihood-based inference has serious lack of robustness against outliers in data and generate drastically different (erroneous) inference in the presence of data contamination. Here, we develop the robust minimum density power divergence estimator and a class of robust Wald-type tests for the beta regression model along with several applications. We derive their asymptotic properties and describe their robustness theoretically through the influence function analyses. Finite sample performances of the proposed estimators and tests are examined through suitable simulation studies and real data applications in the context of health care and psychology. Although we primarily focus on the beta regression models with a fixed dispersion parameter, some indications are also provided for extension to the variable dispersion beta regression models with an application.

Fractional poisson--a simple dose-response model for human norovirus.

PubMed

Messner, Michael J; Berger, Philip; Nappier, Sharon P

2014-10-01

This study utilizes old and new Norovirus (NoV) human challenge data to model the dose-response relationship for human NoV infection. The combined data set is used to update estimates from a previously published beta-Poisson dose-response model that includes parameters for virus aggregation and for a beta-distribution that describes variable susceptibility among hosts. The quality of the beta-Poisson model is examined and a simpler model is proposed. The new model (fractional Poisson) characterizes hosts as either perfectly susceptible or perfectly immune, requiring a single parameter (the fraction of perfectly susceptible hosts) in place of the two-parameter beta-distribution. A second parameter is included to account for virus aggregation in the same fashion as it is added to the beta-Poisson model. Infection probability is simply the product of the probability of nonzero exposure (at least one virus or aggregate is ingested) and the fraction of susceptible hosts. The model is computationally simple and appears to be well suited to the data from the NoV human challenge studies. The model's deviance is similar to that of the beta-Poisson, but with one parameter, rather than two. As a result, the Akaike information criterion favors the fractional Poisson over the beta-Poisson model. At low, environmentally relevant exposure levels (<100), estimation error is small for the fractional Poisson model; however, caution is advised because no subjects were challenged at such a low dose. New low-dose data would be of great value to further clarify the NoV dose-response relationship and to support improved risk assessment for environmentally relevant exposures. © 2014 Society for Risk Analysis Published 2014. This article is a U.S. Government work and is in the public domain for the U.S.A.

Transport modeling of the DIII-D high $${{\\beta}_{p}}$$ scenario and extrapolations to ITER steady-state operation

DOE PAGES

McClenaghan, Joseph; Garofalo, Andrea M.; Meneghini, Orso; ...

2017-08-03

In this study, transport modeling of a proposed ITER steady-state scenario based on DIII-D high poloidal-beta (more » $${{\\beta}_{p}}$$ ) discharges finds that ITB formation can occur with either sufficient rotation or a negative central shear q-profile. The high $${{\\beta}_{p}}$$ scenario is characterized by a large bootstrap current fraction (80%) which reduces the demands on the external current drive, and a large radius internal transport barrier which is associated with excellent normalized confinement. Modeling predictions of the electron transport in the high $${{\\beta}_{p}}$$ scenario improve as $${{q}_{95}}$$ approaches levels similar to typical existing models of ITER steady-state and the ion transport is turbulence dominated. Typical temperature and density profiles from the non-inductive high $${{\\beta}_{p}}$$ scenario on DIII-D are scaled according to 0D modeling predictions of the requirements for achieving a $Q=5$ steady-state fusion gain in ITER with 'day one' heating and current drive capabilities. Then, TGLF turbulence modeling is carried out under systematic variations of the toroidal rotation and the core q-profile. A high bootstrap fraction, high $${{\\beta}_{p}}$$ scenario is found to be near an ITB formation threshold, and either strong negative central magnetic shear or rotation in a high bootstrap fraction are found to successfully provide the turbulence suppression required to achieve $Q=5$.« less

Bayesian inference on risk differences: an application to multivariate meta-analysis of adverse events in clinical trials.

PubMed

Chen, Yong; Luo, Sheng; Chu, Haitao; Wei, Peng

2013-05-01

Multivariate meta-analysis is useful in combining evidence from independent studies which involve several comparisons among groups based on a single outcome. For binary outcomes, the commonly used statistical models for multivariate meta-analysis are multivariate generalized linear mixed effects models which assume risks, after some transformation, follow a multivariate normal distribution with possible correlations. In this article, we consider an alternative model for multivariate meta-analysis where the risks are modeled by the multivariate beta distribution proposed by Sarmanov (1966). This model have several attractive features compared to the conventional multivariate generalized linear mixed effects models, including simplicity of likelihood function, no need to specify a link function, and has a closed-form expression of distribution functions for study-specific risk differences. We investigate the finite sample performance of this model by simulation studies and illustrate its use with an application to multivariate meta-analysis of adverse events of tricyclic antidepressants treatment in clinical trials.

Preliminary Material Properties Handbook, SI Units

DTIC Science & Technology

1999-12-01

5.5 Beta, Near-Beta, and Metastable Titanium Alloys 5-11 References 5-17 Chapter 6. Heat-Resistant Alloys 6.1 General 6-1 6.2 Iron- Chromium ...elements as vanadium, molybdenum, iron, or chromium . In addition to strengthening of titanium by the alloying additions, alpha-beta alloys may be...ALLOYS Heat-resistant alloys are arbitrarily defined as iron alloys richer in alloy content than the 18 percent chromium , 8 percent nickel types

Probability Distribution Estimated From the Minimum, Maximum, and Most Likely Values: Applied to Turbine Inlet Temperature Uncertainty

NASA Technical Reports Server (NTRS)

Holland, Frederic A., Jr.

2004-01-01

Modern engineering design practices are tending more toward the treatment of design parameters as random variables as opposed to fixed, or deterministic, values. The probabilistic design approach attempts to account for the uncertainty in design parameters by representing them as a distribution of values rather than as a single value. The motivations for this effort include preventing excessive overdesign as well as assessing and assuring reliability, both of which are important for aerospace applications. However, the determination of the probability distribution is a fundamental problem in reliability analysis. A random variable is often defined by the parameters of the theoretical distribution function that gives the best fit to experimental data. In many cases the distribution must be assumed from very limited information or data. Often the types of information that are available or reasonably estimated are the minimum, maximum, and most likely values of the design parameter. For these situations the beta distribution model is very convenient because the parameters that define the distribution can be easily determined from these three pieces of information. Widely used in the field of operations research, the beta model is very flexible and is also useful for estimating the mean and standard deviation of a random variable given only the aforementioned three values. However, an assumption is required to determine the four parameters of the beta distribution from only these three pieces of information (some of the more common distributions, like the normal, lognormal, gamma, and Weibull distributions, have two or three parameters). The conventional method assumes that the standard deviation is a certain fraction of the range. The beta parameters are then determined by solving a set of equations simultaneously. A new method developed in-house at the NASA Glenn Research Center assumes a value for one of the beta shape parameters based on an analogy with the normal distribution (ref.1). This new approach allows for a very simple and direct algebraic solution without restricting the standard deviation. The beta parameters obtained by the new method are comparable to the conventional method (and identical when the distribution is symmetrical). However, the proposed method generally produces a less peaked distribution with a slightly larger standard deviation (up to 7 percent) than the conventional method in cases where the distribution is asymmetric or skewed. The beta distribution model has now been implemented into the Fast Probability Integration (FPI) module used in the NESSUS computer code for probabilistic analyses of structures (ref. 2).

Logistic regression of family data from retrospective study designs.

PubMed

Whittemore, Alice S; Halpern, Jerry

2003-11-01

We wish to study the effects of genetic and environmental factors on disease risk, using data from families ascertained because they contain multiple cases of the disease. To do so, we must account for the way participants were ascertained, and for within-family correlations in both disease occurrences and covariates. We model the joint probability distribution of the covariates of ascertained family members, given family disease occurrence and pedigree structure. We describe two such covariate models: the random effects model and the marginal model. Both models assume a logistic form for the distribution of one person's covariates that involves a vector beta of regression parameters. The components of beta in the two models have different interpretations, and they differ in magnitude when the covariates are correlated within families. We describe ascertainment assumptions needed to estimate consistently the parameters beta(RE) in the random effects model and the parameters beta(M) in the marginal model. Under the ascertainment assumptions for the random effects model, we show that conditional logistic regression (CLR) of matched family data gives a consistent estimate beta(RE) for beta(RE) and a consistent estimate for the covariance matrix of beta(RE). Under the ascertainment assumptions for the marginal model, we show that unconditional logistic regression (ULR) gives a consistent estimate for beta(M), and we give a consistent estimator for its covariance matrix. The random effects/CLR approach is simple to use and to interpret, but it can use data only from families containing both affected and unaffected members. The marginal/ULR approach uses data from all individuals, but its variance estimates require special computations. A C program to compute these variance estimates is available at http://www.stanford.edu/dept/HRP/epidemiology. We illustrate these pros and cons by application to data on the effects of parity on ovarian cancer risk in mother/daughter pairs, and use simulations to study the performance of the estimates. Copyright 2003 Wiley-Liss, Inc.

Global patterns of the beta diversity-energy relationship in terrestrial vertebrates

NASA Astrophysics Data System (ADS)

Qian, Hong; Xiao, Ming

2012-02-01

Patterns in beta diversity or species turnover, describing the change in species composition between places, have their wide implication for ecological and evolutionary issues. It is thought that beta diversity increases with increasing energy availability, but very few studies have directly tested this hypothesis. We examined the beta diversity-energy relationship for four classes of terrestrial vertebrates (mammals, birds, reptiles, and amphibians) in ecoregions across the world. The relationship was examined for each class in each of six biogeographic realms. We show that beta diversity is generally higher in areas with higher energy availability, measured as annual potential evapotranspiration. A higher level of beta diversity in areas with higher energy availability may have contributed to the well-known latitudinal diversity gradient (i.e., species richness increases towards the equator).

Ensemble Simulations of Proton Heating in the Solar Wind via Turbulence and Ion Cyclotron Resonance

NASA Astrophysics Data System (ADS)

Cranmer, Steven R.

2014-07-01

Protons in the solar corona and heliosphere exhibit anisotropic velocity distributions, violation of magnetic moment conservation, and a general lack of thermal equilibrium with the other particle species. There is no agreement about the identity of the physical processes that energize non-Maxwellian protons in the solar wind, but a traditional favorite has been the dissipation of ion cyclotron resonant Alfvén waves. This paper presents kinetic models of how ion cyclotron waves heat protons on their journey from the corona to interplanetary space. It also derives a wide range of new solutions for the relevant dispersion relations, marginal stability boundaries, and nonresonant velocity-space diffusion rates. A phenomenological model containing both cyclotron damping and turbulent cascade is constructed to explain the suppression of proton heating at low alpha-proton differential flow speeds. These effects are implemented in a large-scale model of proton thermal evolution from the corona to 1 AU. A Monte Carlo ensemble of realistic wind speeds, densities, magnetic field strengths, and heating rates produces a filled region of parameter space (in a plane described by the parallel plasma beta and the proton temperature anisotropy ratio) similar to what is measured. The high-beta edges of this filled region are governed by plasma instabilities and strong heating rates. The low-beta edges correspond to weaker proton heating and a range of relative contributions from cyclotron resonance. On balance, the models are consistent with other studies that find only a small fraction of the turbulent power spectrum needs to consist of ion cyclotron waves.

Beta-decay half-lives for short neutron rich nuclei involved into the r-process

NASA Astrophysics Data System (ADS)

Panov, I.; Lutostansky, Yu; Thielemann, F.-K.

2018-01-01

The beta-strength function model based on Finite Fermi-Systems Theory is applied for calculations of the beta-decay half-lives for short neutron rich nuclei involved into the r- process. It is shown that the accuracy of beta-decay half-lives of short-lived neutron-rich nuclei is improving with increasing neutron excess and can be used for modeling of nucleosynthesis of heavy nuclei in the r-process.

Effects of Asp-179 mutations in TEMpUC19 beta-lactamase on susceptibility to beta-lactams.

PubMed Central

Vakulenko, S B; Tóth, M; Taibi, P; Mobashery, S; Lerner, S A

1995-01-01

To examine the effect of disruption of the salt bridge (between Arg-164 and Asp-179 [numbering of Ambler et al. (Biochem J. 267:269-272, 1991)]) that anchors the conserved omega-loop in class A beta-lactamases, we obtained mutant enzymes with each of the 19 other amino acid residues replacing Asp-179 in the TEM beta-lactamase encoded by pUC19 and studied the level of resistance to various beta-lactams conferred by each enzyme. All mutations of Asp-179 compromised the level of resistance to ampicillin, but most of them enhanced resistance to ceftazidime. In contrast, mutations of Asp-179 generally impaired the low levels of resistance to cefepime and aztreonam. One might expect to find clinical isolates with mutant TEM beta-lactamases with replacements of Asp-179 that express an expanded spectrum of resistance to beta-lactams including ceftazidime. PMID:7486939

Hidden complexity of free energy surfaces for peptide (protein) folding.

PubMed

Krivov, Sergei V; Karplus, Martin

2004-10-12

An understanding of the thermodynamics and kinetics of protein folding requires a knowledge of the free energy surface governing the motion of the polypeptide chain. Because of the many degrees of freedom involved, surfaces projected on only one or two progress variables are generally used in descriptions of the folding reaction. Such projections result in relatively smooth surfaces, but they could mask the complexity of the unprojected surface. Here we introduce an approach to determine the actual (unprojected) free energy surface and apply it to the second beta-hairpin of protein G, which has been used as a model system for protein folding. The surface is represented by a disconnectivity graph calculated from a long equilibrium folding-unfolding trajectory. The denatured state is found to have multiple low free energy basins. Nevertheless, the peptide shows exponential kinetics in folding to the native basin. Projected surfaces obtained from the present analysis have a simple form in agreement with other studies of the beta-hairpin. The hidden complexity found for the beta-hairpin surface suggests that the standard funnel picture of protein folding should be revisited.

Investigating the principles of recrystallization from glyceride melts.

PubMed

Windbergs, Maike; Strachan, Clare J; Kleinebudde, Peter

2009-01-01

Different lipids were melted and resolidified as model systems to gain deeper insight into the principles of recrystallization processes in lipid-based dosage forms. Solid-state characterization was performed on the samples with differential scanning calorimetry and X-ray powder diffraction. Several recrystallization processes could be identified during storage of the lipid layers. Pure triglycerides that generally crystallize to the metastable alpha-form from the melt followed by a recrystallization process to the stable beta-form with time showed a chain-length-dependent behavior during storage. With increasing chain length, the recrystallization to the stable beta-form was decelerated. Partial glycerides exhibited a more complex recrystallization behavior due to the fact that these substances are less homogenous. Mixtures of a long-chain triglyceride and a partial glyceride showed evidence of some interaction between the two components as the partial glyceride hindered the recrystallization of the triglyceride to the stable beta-form. In addition, the extent of this phenomenon depended on the amount of partial glyceride in the mixture. Based on these results, changes in solid dosage forms based on glycerides during processing and storage can be better understood.

Interaction of Hb South Florida (codon 1; GTG-->ATG) and HbE, with beta-thalassemia (IVS1-1; G-->A): expression of different clinical phenotypes.

PubMed

Tan, Jin-Ai Mary Anne; Tan, Kim-Lian; Omar, Khairul Zaman; Chan, Lee-Lee; Wee, Yong-Chui; George, Elizabeth

2009-09-01

Interactions of different hemoglobin variants with thalassemia alleles can result in various clinical phenotypes. HbE-beta-thalassemia generally manifests with severe anemia where individuals exhibit beta-thalassemia major with regular blood transfusions or beta-thalassemia intermedia with periodic blood transfusions. This study presents a unique Malay family with three beta-globin gene defects-HbE, Hb South Florida, and IVS1-1 (G-->A). HbE activates a cryptic splice site that produces non-functional mRNAs. Hb South Florida is a rare beta-hemoglobin variant, and its interactions with other beta-thalassemia alleles have not been reported. IVS1-1 is a Mediterranean mutation that affects mRNA processing giving rise to beta(o)-thalassemia. Fifteen mutations along the beta-globin gene complex were analyzed using the amplification refractory mutation system. Hb South Florida was identified by direct sequencing using genomic DNA. The affected child with HbE/IVS1-1 produced a beta-thalassemia major phenotype. Compound heterozygosity for Hb South Florida/IVS1-1 produced a beta-thalassemia carrier phenotype in the mother.

Comparative degradation of oomycete, ascomycete, and basidiomycete cell walls by mycoparasitic and biocontrol fungi.

PubMed

Inglis, G D; Kawchuk, L M

2002-01-01

Fourteen fungi (primarily representing mycoparasitic and biocontrol fungi) were tested for their ability to grow on and degrade cell walls (CWs) of an oomycete (Pythium ultimum), ascomycete (Fusarium equisetii), and basidiomycete (Rhizoctonia solani), and their hydrolytic enzymes were characterized. Protein was detected in the cultural medium of eleven of the test isolates, and these fungi significantly degraded CWs over the 14-day duration of the experiment. In general, a greater level of CW degradation occurred for F. equisetii and P. ultimum than for R. solani. Fungi that degraded F. equisetii CWs were Coniothyrium minitans, Gliocladium roseum, Myrothecium verrucaria, Talaromyces flavus, and Trichoderma harzianum. Taxa degrading P ultimum CWs included Chaetomium globosum, Coniothyrium minitans, M. verrucaria, Seimatosporium sp., Talaromyces flavus, Trichoderma hamatum, Trichoderma harzianum, and Trichoderma viride. Production of extracellular protein was highly correlated with CW degradation. Considerable variation in the molecular weights of CW-degrading enzymes were detected among the test fungi and the CW substrates in zymogram electrophoresis. Multivariate analysis between CW degradation and hydrolysis of barley beta-glucan (beta1,3- and beta1,4-glucanases), laminarin (beta1,3- and beta1,6-glucanases), carboxymethyl cellulose (endo-beta1,4-glucanases), colloidal chitin (chitinases), and chitosan (chitosanases) was conducted. For F. equisetii CWs, the regression model accounted for 80% of the variability, and carboxymethyl cellulases acting together with beta-glucanases contributed an R2 of 0.52, whereas chitinases and beta-glucanases alone contributed an R2 of 0.11 and 0.12, respectively. Only 61% of the variability observed in the degradation of P. ultimum CWs was explained by the enzyme classes tested, and primarily beta-glucanases (R2 of 0.53) and carboxymethyl cellulases (R2 of 0.08) alone contributed to CW break down. Too few of the test fungi degraded R. solani CWs to perform multivariate analysis effectively. This study identified several fungi that degraded ascomyceteous and oomyceteous, and to a lesser extent, basidiomycetous CWs. An array of enzymes were implicated in CW degradation.

Maternal and cord plasma concentrations of beta-lipotrophin, beta-endorphin and gamma-lipotrophin at delivery; effect of analgesia.

PubMed

Browning, A J; Butt, W R; Lynch, S S; Shakespear, R A; Crawford, J S

1983-12-01

Maternal venous plasma concentrations of beta-LPH, beta-EP and gamma-LPH were compared in (i) patients undergoing vaginal delivery, 11 with an epidural block and 13 with pethidine and nitrous oxide or no analgesics; (ii) patients delivered by caesarean section, 7 under epidural block and 8 under general anaesthesia. Patients delivered by either method under epidural block had significantly lower levels of all three peptides than those receiving no epidural. There were significant negative correlations between umbilical vein beta-LPH, beta-EP and gamma-LPH concentrations and umbilical artery pH and positive correlations between beta-LPH and beta-EP but not gamma-LPH and cord PCO2 in 29 patients. There was no relation between cord levels of any of the three peptides and the method of analgesia or the route of delivery. Although concentrations of all three peptides were closely correlated to one another in either maternal or cord plasma, there was no relationship between maternal and fetal levels.

Conservation of Oxidative Protein Stabilization in an Insect Homologue of Parkinsonism-Associated Protein DJ-1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lin, Jiusheng; Prahlad, Janani; Wilson, Mark A.

2012-08-21

DJ-1 is a conserved, disease-associated protein that protects against oxidative stress and mitochondrial damage in multiple organisms. Human DJ-1 contains a functionally essential cysteine residue (Cys106) whose oxidation is important for regulating protein function by an unknown mechanism. This residue is well-conserved in other DJ-1 homologues, including two (DJ-1{alpha} and DJ-1{beta}) in Drosophila melanogaster. Because D. melanogaster is a powerful model system for studying DJ-1 function, we have determined the crystal structure and impact of cysteine oxidation on Drosophila DJ-1{beta}. The structure of D. melanogaster DJ-1{beta} is similar to that of human DJ-1, although two important residues in the humanmore » protein, Met26 and His126, are not conserved in DJ-1{beta}. His126 in human DJ-1 is substituted with a tyrosine in DJ-1{beta}, and this residue is not able to compose a putative catalytic dyad with Cys106 that was proposed to be important in the human protein. The reactive cysteine in DJ-1 is oxidized readily to the cysteine-sulfinic acid in both flies and humans, and this may regulate the cytoprotective function of the protein. We show that the oxidation of this conserved cysteine residue to its sulfinate form (Cys-SO{sub 2{sup -}}) results in considerable thermal stabilization of both Drosophila DJ-1{beta} and human DJ-1. Therefore, protein stabilization is one potential mechanism by which cysteine oxidation may regulate DJ-1 function in vivo. More generally, most close DJ-1 homologues are likely stabilized by cysteine-sulfinic acid formation but destabilized by further oxidation, suggesting that they are biphasically regulated by oxidative modification.« less

Minimal modeling of the extratropical general circulation

NASA Technical Reports Server (NTRS)

O'Brien, Enda; Branscome, Lee E.

1989-01-01

The ability of low-order, two-layer models to reproduce basic features of the mid-latitude general circulation is investigated. Changes in model behavior with increased spectral resolution are examined in detail. Qualitatively correct time-mean heat and momentum balances are achieved in a beta-plane channel model which includes the first and third meridional modes. This minimal resolution also reproduces qualitatively realistic surface and upper-level winds and mean meridional circulations. Higher meridional resolution does not result in substantial changes in the latitudinal structure of the circulation. A qualitatively correct kinetic energy spectrum is produced when the resolution is high enough to include several linearly stable modes. A model with three zonal waves and the first three meridional modes has a reasonable energy spectrum and energy conversion cycle, while also satisfying heat and momentum budget requirements. This truncation reproduces the basic mechanisms and zonal circulation features that are obtained at higher resolution. The model performance improves gradually with higher resolution and is smoothly dependent on changes in external parameters.

Circulating lymphocyte levels and relationship with infection status in patients with relapsing-remitting multiple sclerosis treated with daclizumab beta.

PubMed

Giovannoni, Gavin; Wiendl, Heinz; Turner, Benjamin; Umans, Kimberly; Mokliatchouk, Oksana; Castro-Borrero, Wanda; Greenberg, Steven J; McCroskery, Peter; Giannattasio, Giorgio

2017-09-01

Reversible lymphocyte count reductions have occurred following daclizumab beta treatment for relapsing-remitting multiple sclerosis. To analyse total and differential lymphocyte levels and relationship with infection status. In DECIDE, blood samples were collected at 12-week intervals from daclizumab beta- ( n = 919) or intramuscular interferon beta-1a-treated ( n = 922) patients. Infections/serious infections were assessed proximate to grade 2/3 lymphopenia or low CD4 + /CD8 + T-cell counts. Total safety population (TSP) data were additionally analysed from the entire clinical development programme ( n = 2236). Over 96 weeks in DECIDE, mean absolute lymphocyte count (ALC), CD4 + and CD8 + T-cell counts decreased <10% (7.1% vs 1.6%, 9.7% vs 2.0%, 9.3% vs 5.9%: daclizumab beta vs interferon beta-1a, respectively); shifts to ALC below lower limit of normal occurred in 13% versus 15%, respectively. Grade 3 lymphopenia was uncommon (TSP: <1%) and transient. Lymphocyte changes generally occurred within 24 weeks after treatment initiation and were reversible within 12 weeks of discontinuation. In DECIDE, mean CD4 + /CD8 + T-cell counts were similar regardless of infection status. TSP data were consistent with DECIDE. When observed, ALC and CD4 + /CD8 + T-cell count decreases in daclizumab beta-treated patients were generally mild-to-modest, reversible upon treatment discontinuation and not associated with increased risk of infections, including opportunistic infections.

Hydrogen storage and generation system

DOEpatents

Dentinger, Paul M.; Crowell, Jeffrey A. W.

2010-08-24

A system for storing and generating hydrogen generally and, in particular, a system for storing and generating hydrogen for use in an H.sub.2/O.sub.2 fuel cell. The hydrogen storage system uses the beta particles from a beta particle emitting material to degrade an organic polymer material to release substantially pure hydrogen. In a preferred embodiment of the invention, beta particles from .sup.63Ni are used to release hydrogen from linear polyethylene.

Management of hypertension in actively exercising patients. Implications for drug selection.

PubMed

Klaus, D

1989-02-01

In general, rises in systolic blood pressure to over 200 mm Hg during exercise with a workload of 100W are regarded as pathological. Excessive exercise blood pressure values are to be expected in principle in all hypertensives. However, there are so far no generally accepted criteria for diagnosis of isolated systolic exercise hypertension (with normal values of resting blood pressure). The incidence of isolated systolic exercise hypertension is estimated to be about 10% of a selected population. In patients with excessive rises in blood pressure during exercise who want to engage actively in sport, general measures (reduction of obesity, restriction of alcohol and salt intake) and endurance training should be recommended initially. For endurance training, sporting activities that involve dynamic exercise are to be recommended (walking, running, mountain hiking, cycling, swimming, cross-country skiing). Activities involving isometric exercise (rowing, diving, tennis) and sport of a competitive nature are not suitable. In moderately severe and severe hypertension (diastolic blood pressure values in excess of 105 mm Hg), sporting activities and endurance training are contraindicated. If the exercise blood pressure values cannot be lowered below 220 mm Hg with the general measures mentioned, pharmacotherapy is to be considered. The drugs of choice for suppressing excessive rises in blood pressure during exercise are beta-blockers. In this group, beta 1-blockers are to be preferred to non-selective beta-blockers because of the metabolic neutrality of the former. beta-Blockers without intrinsic sympathomimetic activity (ISA) lower the blood pressure-pulse rate product more effectively than beta-blockers with ISA. Alternatively, calcium antagonists of the verapamil type and ACE inhibitors can be employed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adverse CNS-effects of beta-adrenoceptor blockers.

PubMed

Gleiter, C H; Deckert, J

1996-11-01

In 1962 propranolol, the first beta adrenoceptor antagonist (beta blocker), was brought on to the market. There is now a host of different beta blockers available, and these compounds are among the most commonly prescribed groups of drugs. The efficacy of beta blockers has been proven predominantly for the treatment of cardiovascular diseases. Beta blockers are also used for certain types of CNS disorders, such as anxiety disorders, essential tremor and migraine. While low toxicity means that they have a favorable risk-benefit ratio, given the high intensity of use, it is essential to have a comprehensive knowledge of adverse events. Adverse events of beta blockers that can be related to the CNS are quite often neglected, even in textbooks of clinical pharmacology or review articles, and thus often misdiagnosed. The following article, therefore, after summarizing the use of beta blockers for CNS indications, critically reviews the literature on centrally mediated adverse events. General pharmacological features of beta blockers and their molecular basis of action will briefly be addressed to the extent that they are or may become relevant for central nervous pharmacotherapy and side-effects.

A Three-Parameter Generalisation of the Beta-Binomial Distribution with Applications

DTIC Science & Technology

1987-07-01

York. Rust, R.T. and Klompmaker, J.E. (1981). Improving the estimation procedure for the beta binomial t.v. exposure model. Journal of Marketing ... Research . 18, 442-448. Sabavala, D.J. and Morrison, D.G. (1977). Television show loyalty: a beta- binomial model using recall data. Journal of Advertiuing

Using Digital Health Technologies to Understand the Association Between Movement Behaviors and Interstitial Glucose: Exploratory Analysis

PubMed Central

Whelan, Maxine E; Sanders, James P; Sherar, Lauren B; Esliger, Dale W

2018-01-01

Background Acute reductions in postprandial glucose excursions because of movement behaviors have been demonstrated in experimental studies but less so in free-living settings. Objective The objective of this study was to explore the nature of the acute stimulus-response model between accelerometer-assessed physical activity, sedentary time, and glucose variability over 13 days in nondiabetic adults. Methods This study measured physical activity, sedentary time, and interstitial glucose continuously over 13 days in 29 participants (mean age in years: 44.9 [SD 9.1]; female: 59%, 17/29; white: 90%, 26/29; mean body mass index: 25.3 [SD 4.1]) as part of the Sensing Interstitial Glucose to Nudge Active Lifestyles (SIGNAL) research program. Daily minutes spent sedentary, in light activity, and moderate to vigorous physical activity were associated with daily mean glucose, SD of glucose, and mean amplitude of glycemic excursions (MAGE) using generalized estimating equations. Results After adjustment for covariates, sedentary time in minutes was positively associated with a higher daily mean glucose (mmol/L; beta=0.0007; 95% CI 0.00030-0.00103; P<.001), SD of glucose (mmol/L; beta=0.0006; 95% CI 0.00037-0.00081; P<.001), and MAGE (mmol/L; beta=0.002; 95% CI 0.00131-0.00273; P<.001) for those of a lower fitness. Additionally, light activity was inversely associated with mean glucose (mmol/L; beta=−0.0004; 95% CI −0.00078 to −0.00006; P=.02), SD of glucose (mmol/L; beta=−0.0006; 95% CI −0.00085 to −0.00039; P<.001), and MAGE (mmol/L; beta=−0.002; 95% CI −0.00285 to −0.00146; P<.001) for those of a lower fitness. Moderate to vigorous physical activity was only inversely associated with mean glucose (mmol/L; beta=−0.002; 95% CI −0.00250 to −0.00058; P=.002). Conclusions Evidence of an acute stimulus-response model was observed between sedentary time, physical activity, and glucose variability in low fitness individuals, with sedentary time and light activity conferring the most consistent changes in glucose variability. Further work is required to investigate the coupling of movement behaviors and glucose responses in larger samples and whether providing these rich data sources as feedback could induce lifestyle behavior change. PMID:29724703

Efficient triple helix formation by oligodeoxyribonucleotides containing alpha- or beta-2-amino-5-(2-deoxy-D-ribofuranosyl) pyridine residues.

PubMed

Bates, P J; Laughton, C A; Jenkins, T C; Capaldi, D C; Roselt, P D; Reese, C B; Neidle, S

1996-11-01

Triple helices containing C+xGxC triplets are destabilised at physiological pH due to the requirement for base protonation of 2'-deoxycytidine (dC), which has a pKa of 4.3. The C nucleoside 2-amino-5-(2'-deoxy-beta-D-ribofuranosyl)pyridine (beta-AP) is structurally analogous to dC but is considerably more basic, with a pKa of 5.93. We have synthesised 5'-psoralen linked oligodeoxyribonucleotides (ODNs) containing thymidine (dT) and either beta-AP or its alpha-anomer (alpha-AP) and have assessed their ability to form triplexes with a double-stranded target derived from standard deoxynucleotides (i.e. beta-anomers). Third strand ODNs derived from dT and beta-AP were found to have considerably higher binding affinities for the target than the corresponding ODNs derived from dT and either dC or 5-methyl-2'-deoxycytidine (5-Me-dC). ODNs containing dT and alpha-AP also showed enhanced triplex formation with the duplex target and, in addition are more stable in serum-containing medium than standard oligopyrimidine-derived ODNs or ODNs derived from dT and beta-AP. Molecular modelling studies showed that an alpha-anomeric AP nucleotide can be accommodated within an otherwise beta-anomeric triplex with only minor perturbation of the triplex structure. Molecular dynamics (MD) simulations on triplexes containing either the alpha- or beta-anomer of (N1-protonated) AP showed that in both cases the base retained two standard hydrogen bonds to its associated guanine when the 'A-type' model of the triplex was used as the start-point for the simulation, but that bifurcated hydrogen bonds resulted when the alternative 'B-type' triplex model was used. The lack of a differential stability between alpha-AP- and beta-AP-containing triplexes at pH >7, predicted from the behaviour of the B-type models, suggests that the A-type models are more appropriate.

Synthesis and studies of polypeptide materials: Enantioselective polymerization of gamma-benzyl glutamate-N-carboxyanhydride and synthesis of optically active poly(beta-peptides)

NASA Astrophysics Data System (ADS)

Cheng, Jianjun

A class of zero-valent transition metal complexes have been developed by Deming et al for the controlled polymerization of alpha-aminoacid-N-carboxyanhydrides (alpha-NCAs). This discovery provided a superior starting point for the development of enantioselective polymerizations of racemic alpha-NCAs. Bidentate chiral ligands were synthesized and tested for their abilities to induce enantioselective polymerization of gamma-benzyl-glutamate NCA (Glu NCA) when they were coordinated to zero-valent nickel complexes. When optically active 2-pyridinyl oxazoline ligands were mixed with bis(1,5-cyclooctadiene)nickel in THF, chiral nickel complexes were formed that selectively polymerized one enantiomer of Glu NCA over the other. The highest selectivity was observed with the nickel complex of (S)-4-tert-butyl-2-pyridinyl oxazoline, which gave a ratio of enantiomeric polymerization rate constants (kD/kL) of 5.2. It was found that subtle modification of this ligand by incorporation of additional substituents had a substantial impact on initiator enantioselectivities. In separate efforts, methodology was developed for the general synthesis of optically active beta-aminoacid-N-carboxyanhydrides (beta-NCAs) via cyclization of Nbeta-Boc- or Nbeta-Cbz-beta-amino acids using phosphorus tribromide. The beta-NCA molecules could be polymerized in good yields using strong bases or transition metal complexes to give optically active poly(beta-peptides) bearing proteinogenic side chains. The resulting poly(beta-peptides), which have moderate molecular weights, adopt stable helical conformations in solution. Poly(beta-homoglutamate and poly(beta-homolysine), the side-chain deprotected polymers, were found to display pH dependent helix-coil conformation transitions in aqueous solution, similar to their alpha-analogs. A novel method for poly(beta-aspartate) synthesis was developed via the polymerization of L-aspartate alkyl ester beta lactams using metal-amido complexes. Poly(beta-aspartates) bearing short ethylene glycol side chains were obtained with controlled molecular weights and narrow molecular weight distributions when Sc(N(TMS)2)3 was used as initiator for the beta-lactam polymerizations. Polymer chain lengths could be controlled by both stoichiometry and monomer conversion, characteristic of a living polymerization system. Di- and tri-block copoly(beta-peptides) with desired chain lengths were also synthesized using this method. It was found that these techniques were generally applicable for the synthesis of poly(beta-peptides), bearing other proteinogetic side chains. Synthesis and studies of polypeptide materials were extended to unexplored areas by incorporation of both alpha- and beta-amino acid residues into single polymer chains. Two sequence specific polypeptides bearing alternating beta-alpha, or beta-alpha-alpha amino acid residues were synthesized. Both polymers were found to adopt unprecedented stable conformations in solution.

Endosulfan in China 2-emissions and residues.

PubMed

Jia, Hongliang; Sun, Yeqing; Li, Yi-Fan; Tian, Chongguo; Wang, Degao; Yang, Meng; Ding, Yongshen; Ma, Jianmin

2009-05-01

Endosulfan is one of the organochlorine pesticides (OCPs) and also a candidate to be included in a group of new persistent organic pollutants (UNEP 2007). The first national endosulfan usage inventories in China with 1/4 degrees longitude by 1/6 degrees latitude resolution has been reported in an accompanying paper. In the second part of the paper, we compiled the gridded historical emissions and soil residues of endosulfan in China from the usage inventories. Based on the residue/emission data, gridded concentrations of endosulfan in Chinese soil and air have been calculated. These inventories will provide valuable data for the further study of endosulfan. Emission and residue of endosulfan were calculated from endosulfan usage by using a simplified gridded pesticide emission and residue model-SGPERM, which is an integrated modeling system combining mathematical model, database management system, and geographic information system. By using the emission and residue inventories, annual air and soil concentrations of endosulfan in each cell were determined. Historical gridded emission and residue inventories of alpha- and beta-endosulfan in agricultural soil in China with 1/4 degrees longitude by 1/6 degrees latitude resolution have been created. Total emissions were around 10,800 t, with alpha-endosulfan at 7,400 t and beta-endosulfan at 3,400 t from 1994 to 2004. The highest residues were 140 t for alpha-endosulfan and 390 t for beta-endosulfan, and the lowest residues were 0.7 t for alpha-endosulfan and 170 t for beta-endosulfan in 2004 in Chinese agricultural soil where endosulfan was applied. Based on the emission and residue inventories, concentrations of alpha- and beta-endosulfan in Chinese air and agricultural surface soil were also calculated for each grid cell. We have estimated annual averaged air concentrations and the annual minimum and maximum soil concentrations across China. The real concentrations will be different from season to season. Although our model does not consider the transport of the insecticide in the atmosphere, which could be very important in some areas during some special time, the estimated concentrations of endosulfan in Chinese air and soil derived from the endosulfan emission and residue inventories are in general consistent with the published monitoring data. To our knowledge, this work is the first inventory of this kind for endosulfan published on a national scale. Concentrations of the chemical in Chinese air and agricultural surface soil were calculated for each grid cell. Results show that the estimated concentrations of endosulfan in Chinese air and soil agree reasonably well with the monitoring data in general. The gridded endosulfan emission/residue inventories and also the air and soil concentration inventories created in this study will be updated upon availability of new information, including usage and monitoring data. The establishment of these inventories for the OCP is important for both scientific communities and policy makers.

Three-residue turns in alpha/beta-peptides and their application in the design of tertiary structures.

PubMed

Sharma, Gangavaram V M; Nagendar, Pendem; Ramakrishna, Kallaganti V S; Chandramouli, Nagula; Choudhary, Madavi; Kunwar, Ajit C

2008-06-02

A new three-residue turn was serendipitously discovered in alpha/beta hybrid peptides derived from alternating C-linked carbo-beta-amino acids (beta-Caa) and L-Ala residues. The three-residue beta-alpha-beta turn at the C termini, nucleated by a helix at the N termini, resulted in helix-turn (HT) supersecondary structures in these peptides. The turn in the HT motif is stabilized by two H bonds-CO(i-2)-NH(i), with a seven-membered pseudoring (gamma turn) in the backward direction, and NH(i-2)-CO(i), with a 13-membered pseudoring in the forward direction (i being the last residue)--at the C termini. The study was extended to generalize the new three-residue turn (beta-alpha-beta) by using different alpha- and beta-amino acids. Furthermore, the HT motifs were efficiently converted, by an extension with helical oligomers at the C termini, into peptides with novel helix-turn-helix (HTH) tertiary structures. However, this resulted in the destabilization of the beta-alpha-beta turn with the concomitant nucleation of another three-residue turn, alpha-beta-beta, which is stabilized by 11- and 15-membered bifurcated H bonds. Extensive NMR spectroscopic studies were carried out to delineate the secondary and tertiary structures in these peptides, which are further supported by molecular dynamics (MD) investigations.

The involvement of AMPK/GSK3-beta signals in the control of metastasis and proliferation in hepato-carcinoma cells treated with anthocyanins extracted from Korea wild berry Meoru

PubMed Central

2014-01-01

Background Activation of the Wnt pathway is known to promote tumorigenesis and tumor metastasis, and targeting Wnt pathway inhibition has emerged as an attractive approach for controlling tumor invasion and metastasis. The major pathway for inhibiting Wnt is through the degradation of β-catenin by the GSK3-beta/CK1/Axin/APC complex. It was found that Hep3B hepato-carcinoma cells respond to anthocyanins through GSK3-beta-induced suppression of beta-catenin; however, they cannot dephosphorylate GSK3-beta without AMPK activation. Methods We tested the effects of anthocyanins on proliferation and apoptosis by MTT and Annexin V-PI staining in vitro. Mouse xenograft models of hepato-carcinomas were established by inoculation with Hep3B cells, and mice were injected with 50 mg/kg/ml of anthocyanins. In addition, protein levels of p-GSK3-beta, beta-catenin, p-AMPK, MMP-9, VEGF, and Ang-1 were also analyzed using western blot. Results Anthocyanins decrease phospho-GSK3-beta and beta-catenin expression in an in vivo tumor xenograft model, increase AMPK activity in this model, and inhibit cell migration and invasion, possibly by inhibiting MMP-2 (in vitro) and the panendothelial marker, CD31 (in vivo). To elucidate the role of the GSK3-beta/beta-catenin pathway in cancer control, we conditionally inactivated this pathway, using activated AMPK for inhibition. Further, we showed that AMPK siRNA treatment abrogated the ability of anthocyanins to control cell proliferation and metastatic potential, and Compound C, an AMPK inhibitor, could not restore GSK3-beta regulation, as exhibited by anthocyanins in Hep3B cells. Conclusion These observations imply that the AMPK-mediated GSK3-beta/beta-catenin circuit plays crucial roles in inhibiting cancer cell proliferation and metastasis in anthocyanin-treated hepato-carcinoma cells of Meoru origin. PMID:24666969

Beta Function Quintessence Cosmological Parameters and Fundamental Constants I: Power and Inverse Power Law Dark Energy Potentials

NASA Astrophysics Data System (ADS)

Thompson, Rodger I.

2018-04-01

This investigation explores using the beta function formalism to calculate analytic solutions for the observable parameters in rolling scalar field cosmologies. The beta function in this case is the derivative of the scalar ϕ with respect to the natural log of the scale factor a, β (φ )=d φ /d ln (a). Once the beta function is specified, modulo a boundary condition, the evolution of the scalar ϕ as a function of the scale factor is completely determined. A rolling scalar field cosmology is defined by its action which can contain a range of physically motivated dark energy potentials. The beta function is chosen so that the associated "beta potential" is an accurate, but not exact, representation of the appropriate dark energy model potential. The basic concept is that the action with the beta potential is so similar to the action with the model potential that solutions using the beta action are accurate representations of solutions using the model action. The beta function provides an extra equation to calculate analytic functions of the cosmologies parameters as a function of the scale factor that are that are not calculable using only the model action. As an example this investigation uses a quintessence cosmology to demonstrate the method for power and inverse power law dark energy potentials. An interesting result of the investigation is that the Hubble parameter H is almost completely insensitive to the power of the potentials and that ΛCDM is part of the family of quintessence cosmology power law potentials with a power of zero.

Beta function quintessence cosmological parameters and fundamental constants - I. Power and inverse power law dark energy potentials

NASA Astrophysics Data System (ADS)

Thompson, Rodger I.

2018-07-01

This investigation explores using the beta function formalism to calculate analytic solutions for the observable parameters in rolling scalar field cosmologies. The beta function in this case is the derivative of the scalar φ with respect to the natural log of the scale factor a, β (φ)=d φ/d ln (a). Once the beta function is specified, modulo a boundary condition, the evolution of the scalar φ as a function of the scale factor is completely determined. A rolling scalar field cosmology is defined by its action which can contain a range of physically motivated dark energy potentials. The beta function is chosen so that the associated `beta potential' is an accurate, but not exact, representation of the appropriate dark energy model potential. The basic concept is that the action with the beta potential is so similar to the action with the model potential that solutions using the beta action are accurate representations of solutions using the model action. The beta function provides an extra equation to calculate analytic functions of the cosmologies parameters as a function of the scale factor that are not calculable using only the model action. As an example, this investigation uses a quintessence cosmology to demonstrate the method for power and inverse power law dark energy potentials. An interesting result of the investigation is that the Hubble parameter H is almost completely insensitive to the power of the potentials and that Λ cold dark matter is part of the family of quintessence cosmology power-law potentials with a power of zero.

[The relationship of quality of life (QOL) with physical fitness, competence and stress response in elderly in Japan].

PubMed

Uemura, Shinichi; Machida, Kazuhiki

2003-09-01

In order to evaluate the relationship of quality of life (QOL) with physical fitness, competence and stress response in the elderly population in Japan, a cross sectional field survey of elderly subjects was conducted. This survey was taken in Naguri village, Saitama. The data collected included physical fitness, competence, stress response and QOL in addition to demographic variables. As for physical fitness indexes, grip strength (GS), single leg balance with eyes closed (SLB), bar grip ping reaction time (RT), trunk flexion (RF), ten-meter walking time (WT) and vital capacity (VC) were measured. The SF-36 was used for QOL assessment. A total of 120 elderly subjected participated to the survey. There were 42 males (73.5 +/- 5.74 years) and 78 females (74.2 +/- 6.17 years). The associations between physical health parameters in SF-36 and WT were highly significant: physical functioning (beta = -2.96, p < 0.001), role physical (beta = -3.64, p < 0.001), bodily pain (beta = -3.27, p < 0.001) and general health (beta = -3.14, p = 0.001). Psychological stress response had a negative correlation with social functioning (beta = -0.74, p = 0.024), role-emotional (beta = -2.34, p < 0.007) and mental health (beta = -0.97, p = 0.024) as determined by multiple regression analysis. The goodness-of-fit indexes of the structural equation model describing the relationships among physical fitness, competence, stress response and QOL indicated excellent fit to the data with GFI = 0.95 and AGFI = 0.88. Stress response showed relatively stronger influence on QOL than physical fitness or competence. Although there were slight differences in degree of influence, physical fitness, stress response and competence were found to be clearly related to QOL in elderly subjects. To keep good QOL status, it is important to maintain good physical fitness and level of competence and to reduce stress response.

A case of acute generalized exanthematous pustulosis due to amoxicillin-clavulanate with multiple positivity to beta-lactam patch testing.

PubMed

Bomarrito, L; Zisa, G; Delrosso, G; Farinelli, P; Galimberti, M

2013-09-01

We present a case of acute generalized exanthematous pustolosis (AGEP) induced by amoxicillin-clavulanate. Clinical diagnosis was confirmed by symptoms presentation and  histological features (Euroscar score point compatible with definite diagnosis). Patch testing performer six months later confirmed sensitization to the culprit drug and showed positivity also to other beta-lactam antibiotics (penicillin G and cephalexin). We believe that a T cell delayed response to betalactams common ring could be involved.

The beta distribution: A statistical model for world cloud cover

NASA Technical Reports Server (NTRS)

Falls, L. W.

1973-01-01

Much work has been performed in developing empirical global cloud cover models. This investigation was made to determine an underlying theoretical statistical distribution to represent worldwide cloud cover. The beta distribution with probability density function is given to represent the variability of this random variable. It is shown that the beta distribution possesses the versatile statistical characteristics necessary to assume the wide variety of shapes exhibited by cloud cover. A total of 160 representative empirical cloud cover distributions were investigated and the conclusion was reached that this study provides sufficient statical evidence to accept the beta probability distribution as the underlying model for world cloud cover.

Hierarchical multiple regression modelling on predictors of behavior and sexual practices at Takoradi Polytechnic, Ghana.

PubMed

Turkson, Anthony Joe; Otchey, James Eric

2015-01-14

Various psychosocial studies on health related lifestyles lay emphasis on the fact that the perception one has of himself as being at risk of HIV/AIDS infection was a necessary condition for preventive behaviors to be adopted. Hierarchical Multiple Regression models was used to examine the relationship between eight independent variables and one dependent variable to isolate predictors which have significant influence on behavior and sexual practices. A Cross-sectional design was used for the study. Structured close-ended interviewer-administered questionnaire was used to collect primary data. Multistage stratified technique was used to sample views from 380 students from Takoradi Polytechnic, Ghana. A Hierarchical multiple regression model was used to ascertain the significance of certain predictors of sexual behavior and practices. The variables that were extracted from the multiple regression were; for the constant; Beta=14.202, t=2.279, p=0.023, variable is significant; for the marital status; Beta=0.092, t=1.996, p<0.05, variable is significant; for the knowledge on AIDs; Beta=0.090, t=1.996, p<0.05, variable is significant; for the attitude towards HIV/AIDs; =0.486, t=10.575, p<0.001, variable is highly significant. Thus, the best fitting model for predicting behavior and sexual practices was a linear combination of the constant, one's marital status, knowledge on HIV/AIDs and Attitude towards HIV/AIDs., Y(Behavior and sexual practies)= Beta0+Beta1(Marital status)+Beta2(Knowledge on HIV/AIDs issues)+Beta3(Attitude towards HIV/AIDs issues) Beta0, Beta1, Beta2 and Beta3 are respectively 14.201, 2.038, 0.148 and 0.486; the higher the better. Attitude and behavior change education on HIV/AIDs should be intensified in the institution so that students could adopt better lifestyles.

Effects of concomitant use of fibroblast growth factor (FGF)-2 with beta-tricalcium phosphate ({beta}-TCP) on the beagle dog 1-wall periodontal defect model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Anzai, Jun, E-mail: anzai_jun@kaken.co.jp; Department of Periodontology, Osaka University Graduate School of Dentistry, 1-8 Yamadaoka, Suita, Osaka 565-0871; Kitamura, Masahiro, E-mail: kitamura@dent.osaka-u.ac.jp

Research highlights: {yields} Concomitant use of FGF-2 and {beta}-TCP (an osteo-conductive scaffold) significantly promotes periodontal regeneration in the severe periodontitis model (1-wall defect model) of beagle dog. {yields} FGF-2 enhanced new bone formation via {beta}-TCP at the defects. {yields} In particular, FGF-2 dramatically regenerated new periodontal ligament and cementum formations at the defects, that is one of the most important healing outcomes during the process of periodontal regeneration. {yields} Epithelial downgrowth (undesirable wound healing) was decreased by administration of FGF-2. {yields} This manuscript indicates for the first time that concomitant use of FGF-2 and {beta}-TCP is efficacious in regenerating periodontalmore » tissue following severe destruction of the tissue by progression of periodontitis. -- Abstract: The effects of concomitant use of fibroblast growth factor-2 (FGF-2) and beta-tricalcium phosphate ({beta}-TCP) on periodontal regeneration were investigated in the beagle dog 1-wall periodontal defect model. One-wall periodontal defects were created in the mesial portion of both sides of the mandibular first molars, and 0.3% FGF-2 plus {beta}-TCP or {beta}-TCP alone was administered. Radiographic evaluation was performed at 0, 3, and 6 weeks. At 6 weeks, the periodontium with the defect site was removed and histologically analyzed. Radiographic findings showed that co-administration of FGF-2 significantly increased bone mineral contents of the defect sites compared with {beta}-TCP alone. Histologic analysis revealed that the length of the regenerated periodontal ligament, the cementum, distance to the junctional epithelium, new bone height, and area of newly formed bone were significantly increased in the FGF-2 group. No abnormal inflammatory response or ankylosis was observed in either group. These findings indicate the efficacy of concomitant use of FGF-2 and {beta}-TCP as an osteoconductive material for periodontal regeneration following severe destruction by progressive periodontitis.« less

Application of global kinetic models to HMX beta-delta transition and cookoff processes.

PubMed

Wemhoff, Aaron P; Burnham, Alan K; Nichols, Albert L

2007-03-08

The reduction of the number of reactions in kinetic models for both the HMX (octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine) beta-delta phase transition and thermal cookoff provides an attractive alternative to traditional multi-stage kinetic models due to reduced calibration effort requirements. In this study, we use the LLNL code ALE3D to provide calibrated kinetic parameters for a two-reaction bidirectional beta-delta HMX phase transition model based on Sandia instrumented thermal ignition (SITI) and scaled thermal explosion (STEX) temperature history curves, and a Prout-Tompkins cookoff model based on one-dimensional time to explosion (ODTX) data. Results show that the two-reaction bidirectional beta-delta transition model presented here agrees as well with STEX and SITI temperature history curves as a reversible four-reaction Arrhenius model yet requires an order of magnitude less computational effort. In addition, a single-reaction Prout-Tompkins model calibrated to ODTX data provides better agreement with ODTX data than a traditional multistep Arrhenius model and can contain up to 90% fewer chemistry-limited time steps for low-temperature ODTX simulations. Manual calibration methods for the Prout-Tompkins kinetics provide much better agreement with ODTX experimental data than parameters derived from differential scanning calorimetry (DSC) measurements at atmospheric pressure. The predicted surface temperature at explosion for STEX cookoff simulations is a weak function of the cookoff model used, and a reduction of up to 15% of chemistry-limited time steps can be achieved by neglecting the beta-delta transition for this type of simulation. Finally, the inclusion of the beta-delta transition model in the overall kinetics model can affect the predicted time to explosion by 1% for the traditional multistep Arrhenius approach, and up to 11% using a Prout-Tompkins cookoff model.

Programmed disorders of beta-cell development and function as one cause for type 2 diabetes? The GK rat paradigm.

PubMed

Portha, Bernard

2005-01-01

Now that the reduction in beta-mass has been clearly established in humans with type 2 diabetes mellitus (T2DM) 1-4, the debate focuses on the possible mechanisms responsible for decreased beta-cell number and impaired beta-cell function and their multifactorial etiology. Appropriate inbred rodent models are essential tools for identification of genes and environmental factors that increase the risk of abnormal beta-cell function and of T2DM. The information available in the Goto-Kakizaki (GK) rat, one of the best characterized animal models of spontaneous T2DM, are reviewed in such a perspective. We propose that the defective beta-cell mass and function in the GK model reflect the complex interactions of three pathogenic players: (1) several independent loci containing genes causing impaired insulin secretion; (2) gestational metabolic impairment inducing a programming of endocrine pancreas (decreased beta-cell neogenesis) which is transmitted to the next generation; and (3) secondary (acquired) loss of beta-cell differentiation due to chronic exposure to hyperglycemia (glucotoxicity). An important message is that the 'heritable' determinants of T2DM are not simply dependant on genetic factors, but probably involve transgenerational epigenetic responses. Copyright (c) 2005 John Wiley & Sons, Ltd.

Granule cell excitability regulates gamma and beta oscillations in a model of the olfactory bulb dendrodendritic microcircuit

PubMed Central

Osinski, Bolesław L.

2016-01-01

Odors evoke gamma (40–100 Hz) and beta (20–30 Hz) oscillations in the local field potential (LFP) of the mammalian olfactory bulb (OB). Gamma (and possibly beta) oscillations arise from interactions in the dendrodendritic microcircuit between excitatory mitral cells (MCs) and inhibitory granule cells (GCs). When cortical descending inputs to the OB are blocked, beta oscillations are extinguished whereas gamma oscillations become larger. Much of this centrifugal input targets inhibitory interneurons in the GC layer and regulates the excitability of GCs, which suggests a causal link between the emergence of beta oscillations and GC excitability. We investigate the effect that GC excitability has on network oscillations in a computational model of the MC-GC dendrodendritic network with Ca2+-dependent graded inhibition. Results from our model suggest that when GC excitability is low, the graded inhibitory current mediated by NMDA channels and voltage-dependent Ca2+ channels (VDCCs) is also low, allowing MC populations to fire in the gamma frequency range. When GC excitability is increased, the activation of NMDA receptors and other VDCCs is also increased, allowing the slow decay time constants of these channels to sustain beta-frequency oscillations. Our model argues that Ca2+ flow through VDCCs alone could sustain beta oscillations and that the switch between gamma and beta oscillations can be triggered by an increase in the excitability state of a subpopulation of GCs. PMID:27121582

beta-diversity and species accumulation in antarctic coastal benthos: influence of habitat, distance and productivity on ecological connectivity.

PubMed

Thrush, Simon F; Hewitt, Judi E; Cummings, Vonda J; Norkko, Alf; Chiantore, Mariachiara

2010-07-30

High Antarctic coastal marine environments are comparatively pristine with strong environmental gradients, which make them important places to investigate biodiversity relationships. Defining how different environmental features contribute to shifts in beta-diversity is especially important as these shifts reflect both spatio-temporal variations in species richness and the degree of ecological separation between local and regional species pools. We used complementary techniques (species accumulation models, multivariate variance partitioning and generalized linear models) to assess how the roles of productivity, bio-physical habitat heterogeneity and connectivity change with spatial scales from metres to 100's of km. Our results demonstrated that the relative importance of specific processes influencing species accumulation and beta-diversity changed with increasing spatial scale, and that patterns were never driven by only one factor. Bio-physical habitat heterogeneity had a strong influence on beta-diversity at scales <290 km, while the effects of productivity were low and significant only at scales >40 km. Our analysis supports the emphasis on the analysis of diversity relationships across multiple spatial scales and highlights the unequal connectivity of individual sites to the regional species pool. This has important implications for resilience to habitat loss and community homogenisation, especially for Antarctic benthic communities where rates of recovery from disturbance are slow, there is a high ratio of poor-dispersing and brooding species, and high biogenic habitat heterogeneity and spatio-temporal variability in primary production make the system vulnerable to disturbance. Consequently, large areas need to be included within marine protected areas for effective management and conservation of these special ecosystems in the face of increasing anthropogenic disturbance.

Multiple interactions between maternally-activated signalling pathways control Xenopus nodal-related genes.

PubMed

Rex, Maria; Hilton, Emma; Old, Robert

2002-03-01

We have investigated the induction of the six Xenopus nodal-related genes, Xnr1-Xnr6, by maternal determinants. The beta-catenin pathway was modelled by stimulation using Xwnt8, activin-like signalling was modelled by activin, and VegT action was studied by overexpression in animal cap explants. Combinations of factors were examined, and previously unrecognised interactions were revealed in animal caps and whole embryos. For the induction of Xnr5 and Xnr6 in whole embryos, using a beta-catenin antisense morpholino oligonucleotide or a dominant negative XTcf3, we have demonstrated an absolute permissive requirement for the beta-catenin/Tcf pathway, in addition to the requirement for VegT action. In animal caps Xnr5 and Xnr6 are induced in response to VegT overexpression, and this induction is dependent upon the concomitant activation of the beta-catenin pathway that VegT initiates in animal caps. For the induction of Xnr3, VegT interacts negatively so as to inhibit the induction otherwise observed with wnt-signalling alone. The negative effect of VegT is not the result of a general inhibition of wnt-signalling, and does not result from an inhibition of wnt-induced siamois expression. A 294 bp proximal promoter fragment of the Xnr3 gene is sufficient to mediate the negative effect of VegT. Further experiments, employing cycloheximide to examine the dependence of Xnr gene expression upon proteins translated after the mid-blastula stage, demonstrated that Xnrs 4, 5 and 6 are 'primary' Xnr genes whose expression in the late blastula is solely dependent upon factors present before the mid-blastula stage.

Comparative activities of telavancin combined with nafcillin, imipenem, and gentamicin against Staphylococcus aureus.

PubMed

Leonard, Steven N; Supple, Megan E; Gandhi, Ronak G; Patel, Meghna D

2013-06-01

Beta-lactams enhance the killing activity of vancomycin. Due to structural and mechanistic similarities between vancomycin and telavancin, we investigated the activity of telavancin combined with nafcillin and imipenem compared to the known synergistic combination of telavancin and gentamicin. Thirty strains of Staphylococcus aureus, 10 methicillin-susceptible S. aureus (MSSA), 10 methicillin-resistant S. aureus (MRSA), and 10 heterogeneously vancomycin-intermediate S. aureus (hVISA), were tested for synergy by time-kill methodology. Six strains (2 each of MSSA, MRSA, and hVISA) were further evaluated in an in vitro pharmacokinetic/pharmacodynamic (PK/PD) model with simulated regimens of 10 mg/kg of body weight of telavancin once daily alone and combined with 2 g nafcillin every 4 h, 500 mg imipenem every 6 h, or 5 mg/kg gentamicin once daily over 72 h. In the synergy test, 67% of strains displayed synergy with the combination of telavancin and gentamicin, 70% with telavancin and nafcillin, and 63% with telavancin and imipenem. In the PK/PD model, the activities of all three combinations against MRSA and hVISA were superior to all individual drugs alone (P ≤ 0.002) and were similar to each other (P ≥ 0.187). The activities of all three combinations against MSSA were generally similar to each other except for one strain where the combination of telavancin and imipenem was superior to all other regimens (P ≤ 0.011). The activity of the combination of telavancin and beta-lactam agents was similar to that of telavancin and gentamicin against S. aureus, including resistant strains. Because beta-lactam combinations are less likely to be nephrotoxic than telavancin plus gentamicin, these beta-lactam combinations may have clinical utility.

Selective destruction of mouse islet beta cells by human T lymphocytes in a newly-established humanized type 1 diabetic model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhao, Yong, E-mail: yongzhao@uic.edu; Guo, Chengshan; Hwang, David

2010-09-03

Research highlights: {yields} Establish a human immune-mediated type 1 diabetic model in NOD-scid IL2r{gamma}{sup null} mice. {yields} Using the irradiated diabetic NOD mouse spleen mononuclear cells as trigger. {yields} The islet {beta} cells were selectively destroyed by infiltrated human T cells. {yields} The model can facilitate translational research to find a cure for type 1 diabetes. -- Abstract: Type 1 diabetes (T1D) is caused by a T cell-mediated autoimmune response that leads to the loss of insulin-producing {beta} cells. The optimal preclinical testing of promising therapies would be aided by a humanized immune-mediated T1D model. We develop this model inmore » NOD-scid IL2r{gamma}{sup null} mice. The selective destruction of pancreatic islet {beta} cells was mediated by human T lymphocytes after an initial trigger was supplied by the injection of irradiated spleen mononuclear cells (SMC) from diabetic nonobese diabetic (NOD) mice. This resulted in severe insulitis, a marked loss of total {beta}-cell mass, and other related phenotypes of T1D. The migration of human T cells to pancreatic islets was controlled by the {beta} cell-produced highly conserved chemokine stromal cell-derived factor 1 (SDF-1) and its receptor C-X-C chemokine receptor (CXCR) 4, as demonstrated by in vivo blocking experiments using antibody to CXCR4. The specificity of humanized T cell-mediated immune responses against islet {beta} cells was generated by the local inflammatory microenvironment in pancreatic islets including human CD4{sup +} T cell infiltration and clonal expansion, and the mouse islet {beta}-cell-derived CD1d-mediated human iNKT activation. The selective destruction of mouse islet {beta} cells by a human T cell-mediated immune response in this humanized T1D model can mimic those observed in T1D patients. This model can provide a valuable tool for translational research into T1D.« less

Effect of trial-to-trial variability on optimal event-related fMRI design: Implications for Beta-series correlation and multi-voxel pattern analysis

PubMed Central

Abdulrahman, Hunar; Henson, Richard N.

2016-01-01

Functional magnetic resonance imaging (fMRI) studies typically employ rapid, event-related designs for behavioral reasons and for reasons associated with statistical efficiency. Efficiency is calculated from the precision of the parameters (Betas) estimated from a General Linear Model (GLM) in which trial onsets are convolved with a Hemodynamic Response Function (HRF). However, previous calculations of efficiency have ignored likely variability in the neural response from trial to trial, for example due to attentional fluctuations, or different stimuli across trials. Here we compare three GLMs in their efficiency for estimating average and individual Betas across trials as a function of trial variability, scan noise and Stimulus Onset Asynchrony (SOA): “Least Squares All” (LSA), “Least Squares Separate” (LSS) and “Least Squares Unitary” (LSU). Estimation of responses to individual trials in particular is important for both functional connectivity using “Beta-series correlation” and “multi-voxel pattern analysis” (MVPA). Our simulations show that the ratio of trial-to-trial variability to scan noise impacts both the optimal SOA and optimal GLM, especially for short SOAs < 5 s: LSA is better when this ratio is high, whereas LSS and LSU are better when the ratio is low. For MVPA, the consistency across voxels of trial variability and of scan noise is also critical. These findings not only have important implications for design of experiments using Beta-series regression and MVPA, but also statistical parametric mapping studies that seek only efficient estimation of the mean response across trials. PMID:26549299

Development of a new family of conformationally restricted peptides as potent nucleators of beta-turns. Design, synthesis, structure, and biological evaluation of a beta-lactam peptide analogue of melanostatin.

PubMed

Palomo, Claudio; Aizpurua, Jesus M; Benito, Ana; Miranda, José Ignacio; Fratila, Raluca M; Matute, Carlos; Domercq, Maria; Gago, Federico; Martin-Santamaria, Sonsoles; Linden, Anthony

2003-12-31

Novel enantiopure (i)-(beta-lactam)-(Gly)-(i+3) peptide models, defined by the presence of a central alpha-alkyl-alpha-amino-beta-lactam ring placed as the (i+1) residue, have been synthesized in a totally stereocontrolled way by alpha-alkylation of suitable N-[bis(trimethylsilyl)methyl]-beta-lactams. The structural properties of these beta-lactam pseudopeptides have been studied by X-ray crystallography, Molecular Dynamics simulation, and NOESY-restrained NMR simulated annealing techniques, showing a strong tendency to form stable type II or type II' beta-turns either in the solid state or in highly coordinating DMSO solutions. Tetrapeptide models containing syn- or anti-alpha,beta-dialkyl-alpha-amino-beta-lactam rings have also been synthesized and their conformations analyzed, revealing that alpha-alkyl substitution is essential for beta-turn stabilization. A beta-lactam analogue of melanostatin (PLG amide) has also been prepared, characterized as a type-II beta-turn in DMSO-d6 solution, and tested by competitive binding assay as a dopaminergic D2 modulator in rat neuron cultured cells, displaying moderate agonist activity in the micromolar concentration range. On the basis of these results, a novel peptidomimetic design concept, based on the separation of constraint and recognition elements, is proposed.

Vector space methods of photometric analysis - Applications to O stars and interstellar reddening

NASA Technical Reports Server (NTRS)

Massa, D.; Lillie, C. F.

1978-01-01

A multivariate vector-space formulation of photometry is developed which accounts for error propagation. An analysis of uvby and H-beta photometry of O stars is presented, with attention given to observational errors, reddening, general uvby photometry, early stars, and models of O stars. The number of observable parameters in O-star continua is investigated, the way these quantities compare with model-atmosphere predictions is considered, and an interstellar reddening law is derived. It is suggested that photospheric expansion affects the formation of the continuum in at least some O stars.

Gibbs motif sampling: detection of bacterial outer membrane protein repeats.

PubMed Central

Neuwald, A. F.; Liu, J. S.; Lawrence, C. E.

1995-01-01

The detection and alignment of locally conserved regions (motifs) in multiple sequences can provide insight into protein structure, function, and evolution. A new Gibbs sampling algorithm is described that detects motif-encoding regions in sequences and optimally partitions them into distinct motif models; this is illustrated using a set of immunoglobulin fold proteins. When applied to sequences sharing a single motif, the sampler can be used to classify motif regions into related submodels, as is illustrated using helix-turn-helix DNA-binding proteins. Other statistically based procedures are described for searching a database for sequences matching motifs found by the sampler. When applied to a set of 32 very distantly related bacterial integral outer membrane proteins, the sampler revealed that they share a subtle, repetitive motif. Although BLAST (Altschul SF et al., 1990, J Mol Biol 215:403-410) fails to detect significant pairwise similarity between any of the sequences, the repeats present in these outer membrane proteins, taken as a whole, are highly significant (based on a generally applicable statistical test for motifs described here). Analysis of bacterial porins with known trimeric beta-barrel structure and related proteins reveals a similar repetitive motif corresponding to alternating membrane-spanning beta-strands. These beta-strands occur on the membrane interface (as opposed to the trimeric interface) of the beta-barrel. The broad conservation and structural location of these repeats suggests that they play important functional roles. PMID:8520488

Work routines moderate the association between eveningness and poor psychological well-being

PubMed Central

de Souza, Camila Morelatto; Hidalgo, Maria Paz Loayza

2018-01-01

Well-being is a useful screening method for the detection of mood disorders. Evidence associating psychological well-being with sleep-wake patterns exists, as well as associations with sleep-wake patterns, work-related parameters, and perceived self-efficacy. Despite the growing research regarding the relationship between these factors and mental health, there are few studies that analyze them together. OBJECTIVE: To investigate if the association between sleep-wake patterns and psychological well-being is mediated or moderated by perceived self-efficacy, work flexibility and work routines. MATERIAL AND METHODS: This cohort study was performed in southern Brazil. A sample of 987 individuals was analyzed (66.9% women; mean age = 43.9 years). Work routines parameters and work schedule flexibility were evaluated, most participants were farmers (46%) and most worked 7 days a week (69.1%). Munich Chronotype Questionnaire (MCTQ) was administered for evaluation of sleep-wake patterns, General Self-Efficacy Scale (GSE) for assessment the participants’ beliefs about how they coped with daily hassles, and World Health Organization Five-item Well-being Index (WHO-5) for evaluation of psychological well-being levels. Moderation and mediation models were tested. RESULTS: The moderation model showed influences of work end time on the relationship between sleep onset time and psychological well-being (R2 = 0.147; F = 24.16; p<0.001). The final regression model showed an association of psychological well-being with sex (Beta = -0.086; p = 0.004), sleep onset time (Beta = -0.086; p = 0.006), and self-efficacy (Beta = 0.316; p<0.001); the work end time showed association in the interaction with sleep onset time (Beta = -0.075; p = 0.016). CONCLUSION: The findings support the direct association of psychological well-being with sleep-wake patterns and self-efficacy, and show an interaction between work routines and sleep-wake patterns. Our results draw attention to the importance of the interplay between individual and social rhythms in relation to psychological well-being. PMID:29624593

On the phosphorylase activity of GH3 enzymes: A β-N-acetylglucosaminidase from Herbaspirillum seropedicae SmR1 and a glucosidase from Saccharopolyspora erythraea.

PubMed

Ducatti, Diogo R B; Carroll, Madison A; Jakeman, David L

2016-11-29

A phosphorolytic activity has been reported for beta-N-acetylglucosaminidases from glycoside hydrolase family 3 (GH3) giving an interesting explanation for an unusual histidine as catalytic acid/base residue and suggesting that members from this family may be phosphorylases [J. Biol. Chem. 2015, 290, 4887]. Here, we describe the characterization of Hsero1941, a GH3 beta-N-acetylglucosaminidase from the endophytic nitrogen-fixing bacterium Herbaspirillum seropedicae SmR1. The enzyme has significantly higher activity against pNP-beta-D-GlcNAcp (K m  = 0.24 mM, k cat  = 1.2 s -1 , k cat /K m  = 5.0 mM -1 s -1 ) than pNP-beta-D-Glcp (K m  = 33 mM, k cat  = 3.3 × 10 -3 s -1 , k cat /K m  = 9 × 10 -4  mM -1 s -1 ). The presence of phosphate failed to significantly modify the kinetic parameters of the reaction. The enzyme showed a broad aglycone site specificity, being able to hydrolyze sugar phosphates beta-D-GlcNAc 1P and beta-D-Glc 1P, albeit at a fraction of the rate of hydrolysis of aryl glycosides. GH3 beta-glucosidase EryBI, that does not have a histidine as the general acid/base residue, also hydrolyzed beta-D-Glc 1P, at comparable rates to Hsero1941. These data indicate that Hsero1941 functions primarily as a hydrolase and that phosphorolytic activity is likely adventitious. The prevalence of histidine as a general acid/base residue is not predictive, nor correlative, with GH3 beta-N-acetylglucosaminidases having phosphorolytic activity. Copyright © 2016 Elsevier Ltd. All rights reserved.

Model for the alpha and beta shear-mechanical properties of supercooled liquids and its comparison to squalane data

NASA Astrophysics Data System (ADS)

Hecksher, Tina; Olsen, Niels Boye; Dyre, Jeppe C.

2017-04-01

This paper presents data for supercooled squalane's frequency-dependent shear modulus covering frequencies from 10 mHz to 30 kHz and temperatures from 168 K to 190 K; measurements are also reported for the glass phase down to 146 K. The data reveal a strong mechanical beta process. A model is proposed for the shear response of the metastable equilibrium liquid phase of supercooled liquids. The model is an electrical equivalent-circuit characterized by additivity of the dynamic shear compliances of the alpha and beta processes. The nontrivial parts of the alpha and beta processes are each represented by a "Cole-Cole retardation element" defined as a series connection of a capacitor and a constant-phase element, resulting in the Cole-Cole compliance function well-known from dielectrics. The model, which assumes that the high-frequency decay of the alpha shear compliance loss varies with the angular frequency as ω-1 /2, has seven parameters. Assuming time-temperature superposition for the alpha and beta processes separately, the number of parameters varying with temperature is reduced to four. The model provides a better fit to the data than an equally parametrized Havriliak-Negami type model. From the temperature dependence of the best-fit model parameters, the following conclusions are drawn: (1) the alpha relaxation time conforms to the shoving model; (2) the beta relaxation loss-peak frequency is almost temperature independent; (3) the alpha compliance magnitude, which in the model equals the inverse of the instantaneous shear modulus, is only weakly temperature dependent; (4) the beta compliance magnitude decreases by a factor of three upon cooling in the temperature range studied. The final part of the paper briefly presents measurements of the dynamic adiabatic bulk modulus covering frequencies from 10 mHz to 10 kHz in the temperature range from 172 K to 200 K. The data are qualitatively similar to the shear modulus data by having a significant beta process. A single-order-parameter framework is suggested to rationalize these similarities.

Model for the alpha and beta shear-mechanical properties of supercooled liquids and its comparison to squalane data.

PubMed

Hecksher, Tina; Olsen, Niels Boye; Dyre, Jeppe C

2017-04-21

This paper presents data for supercooled squalane's frequency-dependent shear modulus covering frequencies from 10 mHz to 30 kHz and temperatures from 168 K to 190 K; measurements are also reported for the glass phase down to 146 K. The data reveal a strong mechanical beta process. A model is proposed for the shear response of the metastable equilibrium liquid phase of supercooled liquids. The model is an electrical equivalent-circuit characterized by additivity of the dynamic shear compliances of the alpha and beta processes. The nontrivial parts of the alpha and beta processes are each represented by a "Cole-Cole retardation element" defined as a series connection of a capacitor and a constant-phase element, resulting in the Cole-Cole compliance function well-known from dielectrics. The model, which assumes that the high-frequency decay of the alpha shear compliance loss varies with the angular frequency as ω -1/2 , has seven parameters. Assuming time-temperature superposition for the alpha and beta processes separately, the number of parameters varying with temperature is reduced to four. The model provides a better fit to the data than an equally parametrized Havriliak-Negami type model. From the temperature dependence of the best-fit model parameters, the following conclusions are drawn: (1) the alpha relaxation time conforms to the shoving model; (2) the beta relaxation loss-peak frequency is almost temperature independent; (3) the alpha compliance magnitude, which in the model equals the inverse of the instantaneous shear modulus, is only weakly temperature dependent; (4) the beta compliance magnitude decreases by a factor of three upon cooling in the temperature range studied. The final part of the paper briefly presents measurements of the dynamic adiabatic bulk modulus covering frequencies from 10 mHz to 10 kHz in the temperature range from 172 K to 200 K. The data are qualitatively similar to the shear modulus data by having a significant beta process. A single-order-parameter framework is suggested to rationalize these similarities.

Pressure-induced subunit dissociation and unfolding of dimeric beta-lactoglobulin.

PubMed Central

Valente-Mesquita, V L; Botelho, M M; Ferreira, S T

1998-01-01

Effects of hydrostatic pressure on dimeric beta-lactoglobulin A (beta-Lg) were investigated. Application of pressures of up to 3.5 kbar induced a significant red shift ( approximately 11 nm) and a 60% increase in intrinsic fluorescence emission of beta-Lg. These changes were very similar to those induced by guanidine hydrochloride, which caused subunit dissociation and unfolding of beta-Lg. A large hysteresis in the recovery of fluorescence parameters was observed upon decompression of beta-Lg. Pressure-induced dissociation and unfolding were not fully reversible, because of the formation of a nonnative intersubunit disulfide bond that hampered correct refolding of the dimer. Comparison between pressure dissociation/unfolding at 3 degrees C and 23 degrees C revealed a marked destabilization of beta-Lg at low temperature. The stability of beta-Lg toward pressure was significantly enhanced by 1 M NaCl, but not by glycerol (up to 20% v/v). These observations suggest that salt stabilization was not related to a general cosolvent effect, but may reflect charge screening. Interestingly, pressure-induced dissociation/unfolding was completely independent of beta-Lg concentration, in apparent violation of the law of mass action. Possible causes for this anomalous behavior are discussed. PMID:9649408

Lymphotoxin beta receptor (Lt betaR): dual roles in demyelination and remyelination and successful therapeutic intervention using Lt betaR-Ig protein.

PubMed

Plant, Sheila R; Iocca, Heather A; Wang, Ying; Thrash, J Cameron; O'Connor, Brian P; Arnett, Heather A; Fu, Yang-Xin; Carson, Monica J; Ting, Jenny P-Y

2007-07-11

Inflammation mediated by macrophages is increasingly found to play a central role in diseases and disorders that affect a myriad of organs, prominent among these are diseases of the CNS. The neurotoxicant-induced, cuprizone model of demyelination is ideally suited for the analysis of inflammatory events. Demyelination on exposure to cuprizone is accompanied by predictable microglial activation and astrogliosis, and, after cuprizone withdrawal, this activation reproducibly diminishes during remyelination. This study demonstrates enhanced expression of lymphotoxin beta receptor (Lt betaR) during the demyelination phase of this model, and Lt betaR is found in areas enriched with microglial and astroglial cells. Deletion of the Lt betaR gene (Lt betaR-/-) resulted in a significant delay in demyelination but also a slight delay in remyelination. Inhibition of Lt betaR signaling by an Lt betaR-Ig fusion decoy protein successfully delayed demyelination in wild-type mice. Unexpectedly, this Lt betaR-Ig decoy protein dramatically accelerated the rate of remyelination, even after the maximal pathological disease state had been reached. This strongly indicates the beneficial role of Lt betaR-Ig in the delay of demyelination and the acceleration of remyelination. The discrepancy between remyelination rates in these systems could be attributed to developmental abnormalities in the immune systems of Lt betaR-/- mice. These findings bode well for the use of an inhibitory Lt betaR-Ig as a candidate biological therapy in demyelinating disorders, because it is beneficial during both demyelination and remyelination.

Symmetric Fold/Super-Hopf Bursting, Chaos and Mixed-Mode Oscillations in Pernarowski Model of Pancreatic Beta-Cells

NASA Astrophysics Data System (ADS)

Fallah, Haniyeh

Pancreatic beta-cells produce insulin to regularize the blood glucose level. Bursting is important in beta cells due to its relation to the release of insulin. Pernarowski model is a simple polynomial model of beta-cell activities indicating bursting oscillations in these cells. This paper presents bursting behaviors of symmetric type in this model. In addition, it is shown that the current system exhibits the phenomenon of period doubling cascades of canards which is a route to chaos. Canards are also observed symmetrically near folds of slow manifold which results in a chaotic transition between n and n + 1 spikes symmetric bursting. Furthermore, mixed-mode oscillations (MMOs) and combination of symmetric bursting together with MMOs are illustrated during the transition between symmetric bursting and continuous spiking.

Designing Predictive Models for Beta-Lactam Allergy Using the Drug Allergy and Hypersensitivity Database.

PubMed

Chiriac, Anca Mirela; Wang, Youna; Schrijvers, Rik; Bousquet, Philippe Jean; Mura, Thibault; Molinari, Nicolas; Demoly, Pascal

Beta-lactam antibiotics represent the main cause of allergic reactions to drugs, inducing both immediate and nonimmediate allergies. The diagnosis is well established, usually based on skin tests and drug provocation tests, but cumbersome. To design predictive models for the diagnosis of beta-lactam allergy, based on the clinical history of patients with suspicions of allergic reactions to beta-lactams. The study included a retrospective phase, in which records of patients explored for a suspicion of beta-lactam allergy (in the Allergy Unit of the University Hospital of Montpellier between September 1996 and September 2012) were used to construct predictive models based on a logistic regression and decision tree method; a prospective phase, in which we performed an external validation of the chosen models in patients with suspicion of beta-lactam allergy recruited from 3 allergy centers (Montpellier, Nîmes, Narbonne) between March and November 2013. Data related to clinical history and allergy evaluation results were retrieved and analyzed. The retrospective and prospective phases included 1991 and 200 patients, respectively, with a different prevalence of confirmed beta-lactam allergy (23.6% vs 31%, P = .02). For the logistic regression method, performances of the models were similar in both samples: sensitivity was 51% (vs 60%), specificity 75% (vs 80%), positive predictive value 40% (vs 57%), and negative predictive value 83% (vs 82%). The decision tree method reached a sensitivity of 29.5% (vs 43.5%), specificity of 96.4% (vs 94.9%), positive predictive value of 71.6% (vs 79.4%), and negative predictive value of 81.6% (vs 81.3%). Two different independent methods using clinical history predictors were unable to accurately predict beta-lactam allergy and replace a conventional allergy evaluation for suspected beta-lactam allergy. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

A comparison of observation-level random effect and Beta-Binomial models for modelling overdispersion in Binomial data in ecology & evolution.

PubMed

Harrison, Xavier A

2015-01-01

Overdispersion is a common feature of models of biological data, but researchers often fail to model the excess variation driving the overdispersion, resulting in biased parameter estimates and standard errors. Quantifying and modeling overdispersion when it is present is therefore critical for robust biological inference. One means to account for overdispersion is to add an observation-level random effect (OLRE) to a model, where each data point receives a unique level of a random effect that can absorb the extra-parametric variation in the data. Although some studies have investigated the utility of OLRE to model overdispersion in Poisson count data, studies doing so for Binomial proportion data are scarce. Here I use a simulation approach to investigate the ability of both OLRE models and Beta-Binomial models to recover unbiased parameter estimates in mixed effects models of Binomial data under various degrees of overdispersion. In addition, as ecologists often fit random intercept terms to models when the random effect sample size is low (<5 levels), I investigate the performance of both model types under a range of random effect sample sizes when overdispersion is present. Simulation results revealed that the efficacy of OLRE depends on the process that generated the overdispersion; OLRE failed to cope with overdispersion generated from a Beta-Binomial mixture model, leading to biased slope and intercept estimates, but performed well for overdispersion generated by adding random noise to the linear predictor. Comparison of parameter estimates from an OLRE model with those from its corresponding Beta-Binomial model readily identified when OLRE were performing poorly due to disagreement between effect sizes, and this strategy should be employed whenever OLRE are used for Binomial data to assess their reliability. Beta-Binomial models performed well across all contexts, but showed a tendency to underestimate effect sizes when modelling non-Beta-Binomial data. Finally, both OLRE and Beta-Binomial models performed poorly when models contained <5 levels of the random intercept term, especially for estimating variance components, and this effect appeared independent of total sample size. These results suggest that OLRE are a useful tool for modelling overdispersion in Binomial data, but that they do not perform well in all circumstances and researchers should take care to verify the robustness of parameter estimates of OLRE models.

Effect of beta-amyloid block of the fast-inactivating K+ channel on intracellular Ca2+ and excitability in a modeled neuron.

PubMed

Good, T A; Murphy, R M

1996-12-24

beta-Amyloid peptide (A beta), one of the primary protein components of senile plaques found in Alzheimer disease, is believed to be toxic to neurons by a mechanism that may involve loss of intracellular calcium regulation. We have previously shown that A beta blocks the fast-inactivating potassium (A) current. In this work, we show, through the use of a mathematical model, that the A beta-mediated block of the A current could result in increased intracellular calcium levels and increased membrane excitability, both of which have been observed in vitro upon acute exposure to A beta. Simulation results are compared with experimental data from the literature; the simulations quantitatively capture the observed concentration dependence of the neuronal response and the level of increase in intracellular calcium.

Comparative molecular field analysis of fenoterol derivatives: A platform towards highly selective and effective beta(2)-adrenergic receptor agonists.

PubMed

Jozwiak, Krzysztof; Woo, Anthony Yiu-Ho; Tanga, Mary J; Toll, Lawrence; Jimenez, Lucita; Kozocas, Joseph A; Plazinska, Anita; Xiao, Rui-Ping; Wainer, Irving W

2010-01-15

To use a previously developed CoMFA model to design a series of new structures of high selectivity and efficacy towards the beta(2)-adrenergic receptor. Out of 21 computationally designed structures 6 compounds were synthesized and characterized for beta(2)-AR binding affinities, subtype selectivities and functional activities. the best compound is (R,R)-4-methoxy-1-naphthylfelnoterol with K(i)beta(2)-AR=0.28microm, K(i)beta(1)-AR/K(i)beta(2)-AR=573, EC(50cAMP)=3.9nm, EC(50cardio)=16nm. The CoMFA model appears to be an effective predictor of the cardiomocyte contractility of the studied compounds which are targeted for use in congestive heart failure. Copyright 2009 Elsevier Ltd. All rights reserved.

New precision measurements of free neutron beta decay with cold neutrons

DOE PAGES

Baeßler, Stefan; Bowman, James David; Penttilä, Seppo I.; ...

2014-10-14

Precision measurements in free neutron beta decay serve to determine the coupling constants of beta decay, and offer several stringent tests of the standard model. This study describes the free neutron beta decay program planned for the Fundamental Physics Beamline at the Spallation Neutron Source at Oak Ridge National Laboratory, and finally puts it into the context of other recent and planned measurements of neutron beta decay observables.

Dynamics of beta-cell turnover: evidence for beta-cell turnover and regeneration from sources of beta-cells other than beta-cell replication in the HIP rat.

PubMed

Manesso, Erica; Toffolo, Gianna M; Saisho, Yoshifumi; Butler, Alexandra E; Matveyenko, Aleksey V; Cobelli, Claudio; Butler, Peter C

2009-08-01

Type 2 diabetes is characterized by hyperglycemia, a deficit in beta-cells, increased beta-cell apoptosis, and islet amyloid derived from islet amyloid polypeptide (IAPP). These characteristics are recapitulated in the human IAPP transgenic (HIP) rat. We developed a mathematical model to quantify beta-cell turnover and applied it to nondiabetic wild type (WT) vs. HIP rats from age 2 days to 10 mo to establish 1) whether beta-cell formation is derived exclusively from beta-cell replication, or whether other sources of beta-cells (OSB) are present, and 2) to what extent, if any, there is attempted beta-cell regeneration in the HIP rat and if this is through beta-cell replication or OSB. We conclude that formation and maintenance of adult beta-cells depends largely ( approximately 80%) on formation of beta-cells independent from beta-cell duplication. Moreover, this source adaptively increases in the HIP rat, implying attempted beta-cell regeneration that substantially slows loss of beta-cell mass.

[Predicting the outcome in severe injuries: an analysis of 2069 patients from the trauma register of the German Society of Traumatology (DGU)].

PubMed

Rixen, D; Raum, M; Bouillon, B; Schlosser, L E; Neugebauer, E

2001-03-01

On hospital admission numerous variables are documented from multiple trauma patients. The value of these variables to predict outcome are discussed controversially. The aim was the ability to initially determine the probability of death of multiple trauma patients. Thus, a multivariate probability model was developed based on data obtained from the trauma registry of the Deutsche Gesellschaft für Unfallchirurgie (DGU). On hospital admission the DGU trauma registry collects more than 30 variables prospectively. In the first step of analysis those variables were selected, that were assumed to be clinical predictors for outcome from literature. In a second step a univariate analysis of these variables was performed. For all primary variables with univariate significance in outcome prediction a multivariate logistic regression was performed in the third step and a multivariate prognostic model was developed. 2069 patients from 20 hospitals were prospectively included in the trauma registry from 01.01.1993-31.12.1997 (age 39 +/- 19 years; 70.0% males; ISS 22 +/- 13; 18.6% lethality). From more than 30 initially documented variables, the age, the GCS, the ISS, the base excess (BE) and the prothrombin time were the most important prognostic factors to predict the probability of death (P(death)). The following prognostic model was developed: P(death) = 1/1 + e(-[k + beta 1(age) + beta 2(GCS) + beta 3(ISS) + beta 4(BE) + beta 5(prothrombin time)]) where: k = -0.1551, beta 1 = 0.0438 with p < 0.0001, beta 2 = -0.2067 with p < 0.0001, beta 3 = 0.0252 with p = 0.0071, beta 4 = -0.0840 with p < 0.0001 and beta 5 = -0.0359 with p < 0.0001. Each of the five variables contributed significantly to the multifactorial model. These data show that the age, GCS, ISS, base excess and prothrombin time are potentially important predictors to initially identify multiple trauma patients with a high risk of lethality. With the base excess and prothrombin time value, as only variables of this multifactorial model that can be therapeutically influenced, it might be possible to better guide early and aggressive therapy.

Statistical methods for the beta-binomial model in teratology.

PubMed Central

Yamamoto, E; Yanagimoto, T

1994-01-01

The beta-binomial model is widely used for analyzing teratological data involving littermates. Recent developments in statistical analyses of teratological data are briefly reviewed with emphasis on the model. For statistical inference of the parameters in the beta-binomial distribution, separation of the likelihood introduces an likelihood inference. This leads to reducing biases of estimators and also to improving accuracy of empirical significance levels of tests. Separate inference of the parameters can be conducted in a unified way. PMID:8187716

Meta-analysis for deriving age- and gender-specific dose-response relationships between urinary cadmium concentration and {beta} {sub 2}-microglobulinuria under environmental exposure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gamo, Masashi; Ono, Kyoko; Nakanishi, Junko

2006-05-15

A meta-analysis was conducted to derive age- and gender-specific dose-response relationships between urinary cadmium (Cd) concentration and {beta} {sub 2}-microglobulinuria ({beta}2MG-uria) under environmental exposure. {beta}2MG-uria was defined by a cutoff point of 1000 {mu}g {beta} {sub 2}-microglobulin/g creatinine. We proposed a model for describing the relationships among the interindividual variabilities in urinary Cd concentration, the ratio of Cd concentrations in the target organ and in urine, and the threshold Cd concentration in the target organ. The parameters in the model were determined so that good agreement might be achieved between the prevalence rates of {beta}2MG-uria reported in the literature andmore » those estimated by the model. In this analysis, only the data from the literature on populations environmentally exposed to Cd were used. Using the model and estimated parameters, the prevalence rate of {beta}2MG-uria can be estimated for an age- and gender-specific subpopulation for which the distribution of urinary Cd concentrations is known. The maximum permissible level of urinary Cd concentration was defined as the maximum geometric mean of the urinary Cd concentration in an age- and gender-specific subpopulation that would not result in a statistically significant increase in the prevalence rate of {beta}2MG-uria. This was estimated to be approximately 3 {mu}g/g creatinine for a population in a small geographical area and approximately 2 {mu}g/g creatinine for a nationwide population.« less

Differential effects of five 'classical' scorpion {beta}-toxins on rNa{sub v}1.2a and DmNav1 provide clues on species-selectivity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bosmans, Frank; Martin-Eauclaire, Marie-France; Tytgat, Jan

2007-01-01

In general, scorpion {beta}-toxins have been well examined. However, few in-depth studies have been devoted to species selectivity and affinity comparisons on the different voltage-activated Na{sup +} channels since they have become available as cloned channels that can be studied in heterologous expression systems. As a result, their classification is largely historical and dates from early in vivo experiments on mice and cockroach and fly larvae. In this study, we aimed to provide an updated overview of selectivity and affinity of scorpion {beta}-toxins towards voltage-activated Na{sup +} channels of vertebrates or invertebrates. As pharmacological tools, we used the classic {beta}-toxinsmore » AaHIT, Css II, Css IV, Css VI and Ts VII and tested them on the neuronal vertebrate voltage-activated Na{sup +} channel, rNa{sub v}1.2a. For comparison, its invertebrate counterpart, DmNav1, was also tested. Both these channels were expressed in Xenopus laevis oocytes and the currents measured with the two-electrode voltage-clamp technique. We supplemented this data with several binding displacement studies on rat brain synaptosomes. The results lead us to propose a general classification and a novel nomenclature of scorpion {beta}-toxins based on pharmacological activity.« less

Human APC sequesters beta-catenin even in the absence of GSK-3beta in a Drosophila model.

PubMed

Rao, P R; Makhijani, K; Shashidhara, L S

2008-04-10

There have been conflicting reports on the requirement of GSK-3beta-mediated phosphorylation of the tumor suppressor adenomatous polyposis coli (APC) vis-à-vis its ability to bind and degrade beta-catenin. Using a unique combination of loss of function for Shaggy/GSK-3beta and a gain of function for human APC in Drosophila, we show that misexpressed human APC (hAPC) can still sequester Armadillo/beta-catenin. In addition, human APC could suppress gain of Wnt/Wingless phenotypes associated with loss of Shaggy/GSK-3beta activity, suggesting that sequestered Armadillo/beta-catenin is non-functional. Based on these studies, we propose that binding per se of beta-catenin by APC does not require phosphorylation by GSK-3beta.

Electroencephalographic response following midazolam-induced general anesthesia: relationship to plasma and effect-site midazolam concentrations.

PubMed

Miyake, Wakako; Oda, Yutaka; Ikeda, Yuko; Hagihira, Satoshi; Iwaki, Hiroyoshi; Asada, Akira

2010-06-01

To examine the relationships between effect-site concentrations and electroencephalographic parameters after the induction of general anesthesia with midazolam. Twenty-four patients with American Society of Anesthesiologists status I or II were randomly allocated to receive either an intravenous (i.v.) bolus of midazolam 0.2 mg kg(-1) (small-dose group, n = 12) or 0.3 mg kg(-1) (large-dose group, n = 12) for induction of general anesthesia in a double-blind experimental design. The bispectral index (BIS), 95% spectral edge frequency (SEF95), spectral power density, and plasma concentrations of midazolam were measured for 60 min following the induction of general anesthesia. Plasma and simulated effect-site concentrations of midazolam were significantly higher in the large-dose group than in the small-dose group (P = 0.005 and <0.001, respectively). There was a correlation between the relative beta ratio and BIS (r (2) = 0.30, P < 0.001; n = 168); however, effect-site concentrations of midazolam showed no association with BIS, relative beta ratio, or SEF95 (r (2) = 0.07, 0.11 and 0.01, respectively; n = 168). The electroencephalographic spectral power density in the beta-band (>/=13 and <30 Hz) was significantly increased after induction and was significantly larger in the large-dose group than in the small-dose group (P = 0.009). Following the induction of general anesthesia with i.v. midazolam 0.2 or 0.3 mg kg(-1), the BIS was positively correlated with the relative beta ratio. Despite a rapid decrease in the plasma and effect-site concentrations of midazolam, the average BIS remained >60 for 60 min after induction, reflecting an increased power of the electroencephalographic high-frequency band.

Structural relaxation in the hydrogen-bonding liquids N-methylacetamide and water studied by optical Kerr effect spectroscopy.

PubMed

Turton, David A; Wynne, Klaas

2008-04-21

Structural relaxation in the peptide model N-methylacetamide (NMA) is studied experimentally by ultrafast optical Kerr effect spectroscopy over the normal-liquid temperature range and compared to the relaxation measured in water at room temperature. It is seen that in both hydrogen-bonding liquids, beta relaxation is present, and in each case, it is found that this can be described by the Cole-Cole function. For NMA in this temperature range, the alpha and beta relaxations are each found to have an Arrhenius temperature dependence with indistinguishable activation energies. It is known that the variations on the Debye function, including the Cole-Cole function, are unphysical, and we introduce two general modifications: One allows for the initial rise of the function, determined by the librational frequencies, and the second allows the function to be terminated in the alpha relaxation.

Contribution from neutrino Yukawa couplings to lepton electric dipole moments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Farzan, Yasaman; Scuola Internazionale di Studi Avanzati; Peskin, Michael E.

2004-11-01

To explain the observed neutrino masses through the seesaw mechanism, a supersymmetric generalization of the standard model should include heavy right-handed neutrino supermultiplets. Then the neutrino Yukawa couplings can induce CP violation in the lepton sector. In this paper, we compute the contribution of these CP violating terms to lepton electric dipole moments. We introduce a new formalism that makes use of supersymmetry to expose the Glashow-Iliopoulos-Maiani cancellations. In the region of small tan{beta}, we find a different result from that given previously by Ellis, Hisano, Raidal, and Shimizu. We confirm the structure found by this group, but with amore » much smaller overall coefficient. In the region of large tan{beta}, we recompute the leading term that has been identified by Masina and confirm her result up to minor factors. We discuss the implications of these results for constraints on the Y{sub {nu}}.« less

The Contribution from Neutrino Yukawa Couplings to Lepton Electric Dipole Moments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Farzan, Y

2004-05-24

To explain the observed neutrino masses through the seesaw mechanism, a supersymmetric generalization of the Standard Model should include heavy right-handed neutrino supermultiplets. Then the neutrino Yukawa couplings can induce CP violation in the lepton sector. In this paper, we compute the contribution of these CP violating terms to lepton electric dipole moments. We introduce a new formalism that makes use of supersymmetry to expose the GIM cancellations. In the region of small tan {beta}, we find a different result from that given previously by Ellis, Hisano, Raidal, and Shimizu. We confirm the structure found by this group, but withmore » a much smaller overall coefficient. In the region of large tan {beta}, we recompute the leading term that has been identified by Masina and confirm her result up to minor factors. We discuss the implications of these results for constraints on the Y{sub v}.« less

Confirmatory and quantitative analysis of beta-lactam antibiotics in bovine kidney tissue by dispersive solid-phase extraction and liquid chromatography-tandem mass spectrometry.

PubMed

Fagerquist, Clifton K; Lightfield, Alan R; Lehotay, Steven J

2005-03-01

A simple, rapid, rugged, sensitive, and specific method for the confirmation and quantitation of 10 beta-lactam antibiotics in fortified and incurred bovine kidney tissue has been developed. The method uses a simple solvent extraction, dispersive solid-phase extraction (dispersive-SPE) cleanup, and liquid chromatography-tandem mass spectrometry (LC/MS/MS) for confirmation and quantitation. Dispersive-SPE greatly simplifies and accelerates sample cleanup and improves overall recoveries compared with conventional SPE cleanup. The beta-lactam antibiotics tested were as follows: deacetylcephapirin (an antimicrobial metabolite of cephapirin), amoxicillin, desfuroylceftiofur cysteine disulfide (DCCD, an antimicrobial metabolite of ceftiofur), ampicillin, cefazolin, penicillin G, oxacillin, cloxacillin, naficillin, and dicloxacillin. Average recoveries of fortified samples were 70% or better for all beta-lactams except DCCD, which had an average recovery of 58%. The LC/MS/MS method was able to demonstrate quantitative recoveries at established tolerance levels and provide confirmatory data for unambiguous analyte identification. The method was also tested on 30 incurred bovine kidney samples obtained from the USDA Food Safety and Inspection Service, which had previously tested the samples using the approved semiquantitative microbial assay. The results from the quantitative LC/MS/MS analysis were in general agreement with the microbial assay for 23 samples although the LC/MS/MS method was superior in that it could specifically identify which beta-lactam was present and quantitate its concentration, whereas the microbial assay could only identify the type of beta-lactam present and report a concentration with respect to the microbial inhibition of a penicillin G standard. In addition, for 6 of the 23 samples, LC/MS/MS analysis detected a penicillin and a cephalosporin beta-lactam, whereas the microbial assay detected only a penicillin beta-lactam. For samples that do not fall into the "general agreement" category, the most serious discrepancy involves two samples where the LC/MS/MS method detected a violative level of a cephalosporin beta-lactam (deacetylcephapirin) in the first sample and a possibly violative level of desfuroylceftiofur in the second, whereas the microbial assay identified the two samples as having only violative levels of a penicillin beta-lactam.

Gene Editing and Human Pluripotent Stem Cells: Tools for Advancing Diabetes Disease Modeling and Beta-Cell Development.

PubMed

Millette, Katelyn; Georgia, Senta

2017-10-05

This review will focus on the multiple approaches to gene editing and address the potential use of genetically modified human pluripotent stem cell-derived beta cells (SC-β) as a tool to study human beta-cell development and model their function in diabetes. We will explore how new variations of CRISPR/Cas9 gene editing may accelerate our understanding of beta-cell developmental biology, elucidate novel mechanisms that establish and regulate beta-cell function, and assist in pioneering new therapeutic modalities for treating diabetes. Improvements in CRISPR/Cas9 target specificity and homology-directed recombination continue to advance its use in engineering stem cells to model and potentially treat disease. We will review how CRISPR/Cas9 gene editing is informing our understanding of beta-cell development and expanding the therapeutic possibilities for treating diabetes and other diseases. Here we focus on the emerging use of gene editing technology, specifically CRISPR/Cas9, as a means of manipulating human gene expression to gain novel insights into the roles of key factors in beta-cell development and function. Taken together, the combined use of SC-β cells and CRISPR/Cas9 gene editing will shed new light on human beta-cell development and function and accelerate our progress towards developing new therapies for patients with diabetes.

Attitudes towards and knowledge about homosexuality among medical students in Zagreb.

PubMed

Grabovac, Igor; Abramović, Marija; Komlenović, Gordana; Milosević, Milan; Mustajbegović, Jadranka

2014-03-01

The aim of the study was to investigate whether students in their fifth and sixth years of medical school in Zagreb have homophobic attitudes and assess their knowledge about homosexuality. A survey was conducted among fifth and sixth year medical students during the 2009/2010 academic year. The survey consisted of general demographic data, two validated questionnaires--"Knowledge about Homosexuality Questionnaire" and "Heterosexual Attitudes towards Homosexuality Scale"--and questions about personal experiences created for this study. The mean knowledge scores were X = 14.8 out of 20. Furthermore, gender differences in attitudes were observed, indicating less negative attitudes among the female participants. The regression model was significant (ANOVA: Sum of Squares = 38.065; df = 17, Mean Square= 2239, F = 10.6; p < 0.001) with 38% of explained variance. The significant predictor variables that indicate lower attitudes about homosexuality score were female gender (beta= -0.14, p = 0.015), sixth year of study (beta = -0.16, p = 0.009) and more knowledge about homosexuality (beta = -0.48, p < 0.001). Negative attitudes are present among the students; therefore, educational efforts should be included in the curricula of medical schools to diminish the negative perceptions of the lesbian, gay, bisexual and transgender community.

Allyl m-Trifluoromethyldiazirine Mephobarbital: An Unusually Potent Enantioselective and Photoreactive Barbiturate General Anesthetic

DOE Office of Scientific and Technical Information (OSTI.GOV)

Savechenkov, Pavel Y.; Zhang, Xi; Chiara, David C.

2012-12-10

We synthesized 5-allyl-1-methyl-5-(m-trifluoromethyl-diazirynylphenyl)barbituric acid (14), a trifluoromethyldiazirine-containing derivative of general anesthetic mephobarbital, separated the racemic mixture into enantiomers by chiral chromatography, and determined the configuration of the (+)-enantiomer as S by X-ray crystallography. Additionally, we obtained the {sup 3}H-labeled ligand with high specific radioactivity. R-(-)-14 is an order of magnitude more potent than the most potent clinically used barbiturate, thiopental, and its general anesthetic EC{sub 50} approaches those for propofol and etomidate, whereas S-(+)-14 is 10-fold less potent. Furthermore, at concentrations close to its anesthetic potency, R-(-)-14 both potentiated GABA-induced currents and increased the affinity for the agonist muscimol inmore » human {alpha}1{beta}2/3{gamma}2L GABA{sub A} receptors. Finally, R-(-)-14 was found to be an exceptionally efficient photolabeling reagent, incorporating into both {alpha}1 and {beta}3 subunits of human {alpha}1{beta}3 GABAA receptors. These results indicate R-(-)-14 is a functional general anesthetic that is well-suited for identifying barbiturate binding sites on Cys-loop receptors.« less

A kinetic model for beta-amyloid adsorption at the air/solution interface and its implication to the beta-amyloid aggregation process.

PubMed

Jiang, Dianlu; Dinh, Kim Lien; Ruthenburg, Travis C; Zhang, Yi; Su, Lei; Land, Donald P; Zhou, Feimeng

2009-03-12

At the air/buffer solution interface the kinetics of adsorption of amyloid beta peptide, Abeta(1-42), whose bulk concentration (submicromolar) is more than 2 orders of magnitude lower than that typically used in other in vitro aggregation studies, has been studied using a Langmuir-Blodgett trough. The pressure-time curves exhibit a lag phase, wherein the surface pressure essentially remains at zero, and a rising phase, corresponding to the Abeta adsorption at the interface. The duration of the lag phase was found to be highly dependent on both the Abeta bulk concentration and the solution temperature. A large activation energy (62.2 +/- 4.1 KJ/mol) was determined and the apparent adsorption rate constant was found to be linearly dependent on the Abeta bulk concentration. Attenuated total reflection-IR spectra of the adsorbed Abeta transferred to a solid substrate and circular dichroism measurements of Abeta in the solution layer near the interface reveal that the natively unstructured Abeta in the bulk undergo a conformation change (folding) to mainly the alpha-helical structure. The results suggest that, prior to the adsorption step, an equilibrium between Abeta conformations is established within the subsurface. The kinetic equation derived from this model confirms that the overall Abeta adsorption is kinetically controlled and the apparent rate constant is proportional to the Abeta bulk concentration. This model also indicates that interfaces such as cell membranes and lipid bilayers may facilitate Abeta aggregation/ fibrillation by providing a thin hydrophobic layer adjacent to the interface for the initial A/beta conformation change (misfolding) and accumulation. Such a preconcentration effect offers a plausible explanation of the fact that Abeta fibrillation occurs in vivo at nanomolar concentrations. Another important biological implication from our work is that Abeta misfolding may occur before its adsorption onto a cell membrane. This general kinetic model should also find applications in adsorption studies of other types of biomolecules whose overall kinetics exhibits a lag phase that is dependent on the bulk concentration of the adsorbate.

A structural equation model of the determinants of malnutrition among children in rural Kelantan, Malaysia.

PubMed

Cheah, Whye Lian; Muda, Wan Abdul Manan Wan; Zamh, Zabidi-Hussin

2010-01-01

Many studies had shown that poor growth in children is associated with malnutrition. The underlying factors are diverse, multisectoral and interrelated, ranging from biological to social, cultural and economically related. Because the highest levels of under-nutrition worldwide are found in South Asia, it is essential that policymakers in the region understand the underlying determinants, in order to design effective public health intervention programs. This is especially so if public resources are limited. The purpose of this cross-sectional study was to examine causal relationships among the biological, behavioural and environmental factors related to malnutrition in children aged 5 years and under. The instrument used in this study was based on a previously described conceptual framework for malnutrition in children, and tested for its psycometric component, using both qualitative and quantitative methods. As well as the use of a questionnaire, anthropometric and dietary data were collected from 295 children aged 5 years and below, randomly selected from clinics in Tumpat, Kelantan. The proposed model was tested and modified using structural equation modelling (AMOS software: ADC, Chicago, IL, USA). The modified model fitted the data adequately. The results demonstrated that an environmental construct (with factors that included total household income beta = 0.68, p <0.01; total expenditure beta = 0.67, p <0.01; number of rooms in the house beta = 0.46, p <0.01; and socioeconomic status beta = 0.71, p <0.01) had a significant effect on malnutrition. Neither the biological nor behavioural constructs had significant effects. These findings provide useful insights into the importance of focusing on environmental factors as the main target when designing intervention programs. This information will be useful for the prioritization of preventive programs when resources are limited, especially in a rural setting. Future studies should focus on the issues of the ability of the households to meet their basic needs, inequality in the population, and the effectiveness of intervention at both micro and macro levels. This study focused on a rural community, therefore the results can only be generalized to areas with similar characteristics.

A neural mass model of basal ganglia nuclei simulates pathological beta rhythm in Parkinson's disease

NASA Astrophysics Data System (ADS)

Liu, Fei; Wang, Jiang; Liu, Chen; Li, Huiyan; Deng, Bin; Fietkiewicz, Chris; Loparo, Kenneth A.

2016-12-01

An increase in beta oscillations within the basal ganglia nuclei has been shown to be associated with movement disorder, such as Parkinson's disease. The motor cortex and an excitatory-inhibitory neuronal network composed of the subthalamic nucleus (STN) and the external globus pallidus (GPe) are thought to play an important role in the generation of these oscillations. In this paper, we propose a neuron mass model of the basal ganglia on the population level that reproduces the Parkinsonian oscillations in a reciprocal excitatory-inhibitory network. Moreover, it is shown that the generation and frequency of these pathological beta oscillations are varied by the coupling strength and the intrinsic characteristics of the basal ganglia. Simulation results reveal that increase of the coupling strength induces the generation of the beta oscillation, as well as enhances the oscillation frequency. However, for the intrinsic properties of each nucleus in the excitatory-inhibitory network, the STN primarily influences the generation of the beta oscillation while the GPe mainly determines its frequency. Interestingly, describing function analysis applied on this model theoretically explains the mechanism of pathological beta oscillations.

Distinct modes of gene regulation by a cell-specific transcriptional activator.

PubMed

Sengupta, Tanushri; Cohet, Nathalie; Morlé, François; Bieker, James J

2009-03-17

The architectural layout of a eukaryotic RNA polymerase II core promoter plays a role in general transcriptional activation. However, its role in tissue-specific expression is not known. For example, differing modes of its recognition by general transcription machinery can provide an additional layer of control within which a single tissue-restricted transcription factor may operate. Erythroid Kruppel-like factor (EKLF) is a hematopoietic-specific transcription factor that is critical for the activation of subset of erythroid genes. We find that EKLF interacts with TATA binding protein-associated factor 9 (TAF9), which leads to important consequences for expression of adult beta-globin. First, TAF9 functionally supports EKLF activity by enhancing its ability to activate the beta-globin gene. Second, TAF9 interacts with a conserved beta-globin downstream promoter element, and ablation of this interaction by beta-thalassemia-causing mutations decreases its promoter activity and disables superactivation. Third, depletion of EKLF prevents recruitment of TAF9 to the beta-globin promoter, whereas depletion of TAF9 drastically impairs beta-promoter activity. However, a TAF9-independent mode of EKLF transcriptional activation is exhibited by the alpha-hemoglobin-stabilizing protein (AHSP) gene, which does not contain a discernable downstream promoter element. In this case, TAF9 does not enhance EKLF activity and depletion of TAF9 has no effect on AHSP promoter activation. These studies demonstrate that EKLF directs different modes of tissue-specific transcriptional activation depending on the architecture of its target core promoter.

Structure and Active Stie Residues of Pg1D, an N-Acetyltransferase from the Bacillosamine Synthetic Pathway Required for N-Glycan Synthesis in Campylobacter jejuni

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rangarajan,E.; Ruane, K.; Sulea, T.

2008-01-01

Campylobacter jejuni is highly unusual among bacteria in forming N-linked glycoproteins. The heptasaccharide produced by its pgl system is attached to protein Asn through its terminal 2, 4-diacetamido-2, 4,6-trideoxy-d-Glc (QuiNAc4NAc or N, N'-diacetylbacillosamine) moiety. The crucial, last part of this sugar's synthesis is the acetylation of UDP-2-acetamido-4-amino-2, 4,6-trideoxy-d-Glc by the enzyme PglD, with acetyl-CoA as a cosubstrate. We have determined the crystal structures of PglD in CoA-bound and unbound forms, refined to 1.8 and 1.75 Angstroms resolution, respectively. PglD is a trimer of subunits each comprised of two domains, an N-terminal {alpha}/{beta}-domain and a C-terminal left-handed {beta}-helix. Few structural differencesmore » accompany CoA binding, except in the C-terminal region following the {beta}-helix (residues 189-195), which adopts an extended structure in the unbound form and folds to extend the {beta}-helix upon binding CoA. Computational molecular docking suggests a different mode of nucleotide-sugar binding with respect to the acetyl-CoA donor, with the molecules arranged in an 'L-shape', compared with the 'in-line' orientation in related enzymes. Modeling indicates that the oxyanion intermediate would be stabilized by the NH group of Gly143', with His125' the most likely residue to function as a general base, removing H+ from the amino group prior to nucleophilic attack at the carbonyl carbon of acetyl-CoA. Site-specific mutations of active site residues confirmed the importance of His125', Glu124', and Asn118. We conclude that Asn118 exerts its function by stabilizing the intricate hydrogen bonding network within the active site and that Glu124' may function to increase the pKa of the putative general base, His125'.« less

Transcriptional regulatory dynamics of the hypothalamic-pituitary-gonadal axis and its peripheral pathways as impacted by the 3-beta HSD inhibitor Trilostane in zebrafish (Danio rerio)

EPA Science Inventory

To identify transcription factors (TFs), members of hypothalamic-pituitary- gonadal axis (HPG-axis), TF networks and signaling pathways underlying generalized effects of 3-beta hydroxysteroid dehydrogenase (HSD3B) inhibition, reproductively mature zebrafish (Danio rerio) were exp...

Chaperones of F[subscript 1]-ATPase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ludlam, Anthony; Brunzelle, Joseph; Pribyl, Thomas

2009-09-25

Mitochondrial F{sub 1}-ATPase contains a hexamer of alternating {alpha} and {beta} subunits. The assembly of this structure requires two specialized chaperones, Atp11p and Atp12p, that bind transiently to {beta} and {alpha}. In the absence of Atp11p and Atp12p, the hexamer is not formed, and {alpha} and {beta} precipitate as large insoluble aggregates. An early model for the mechanism of chaperone-mediated F{sub 1} assembly (Wang, Z. G., Sheluho, D., Gatti, D. L., and Ackerman, S. H. (2000) EMBO J. 19, 1486--1493) hypothesized that the chaperones themselves look very much like the {alpha} and {beta} subunits, and proposed an exchange of Atp11pmore » for {alpha} and of Atp12p for {beta}; the driving force for the exchange was expected to be a higher affinity of {alpha} and {beta} for each other than for the respective chaperone partners. One important feature of this model was the prediction that as long as Atp11p is bound to {beta} and Atp12p is bound to {alpha}, the two F{sub 1} subunits cannot interact at either the catalytic site or the noncatalytic site interface. Here we present the structures of Atp11p from Candida glabrata and Atp12p from Paracoccus denitrificans, and we show that some features of the Wang model are correct, namely that binding of the chaperones to {alpha} and {beta} prevents further interactions between these F1 subunits. However, Atp11p and Atp12p do not resemble {alpha} or {beta}, and it is instead the F{sub 1} {gamma} subunit that initiates the release of the chaperones from {alpha} and {beta} and their further assembly into the mature complex.« less

Burnout Subtypes and Absence of Self-Compassion in Primary Healthcare Professionals: A Cross-Sectional Study

PubMed Central

Montero-Marin, Jesus; Zubiaga, Fernando; Cereceda, Maria; Piva Demarzo, Marcelo Marcos; Trenc, Patricia; Garcia-Campayo, Javier

2016-01-01

Background Primary healthcare professionals report high levels of distress and burnout. A new model of burnout has been developed to differentiate three clinical subtypes: ‘frenetic’, ‘underchallenged’ and ‘worn-out’. The aim of this study was to confirm the validity and reliability of the burnout subtype model in Spanish primary healthcare professionals, and to assess the explanatory power of the self-compassion construct as a possible protective factor. Method The study employed a cross-sectional design. A sample of n = 440 Spanish primary healthcare professionals (214 general practitioners, 184 nurses, 42 medical residents) completed the Burnout Clinical Subtype Questionnaire (BCSQ-36), the Maslach Burnout Inventory General Survey (MBI-GS), the Self-Compassion Scale (SCS), the Utrecht Work Engagement Scale (UWES) and the Positive and Negative Affect Schedule (PANAS). The factor structure of the BCSQ-36 was estimated using confirmatory factor analysis (CFA) by the unweighted least squares method from polychoric correlations. Internal consistency (R) was assessed by squaring the correlation between the latent true variable and the observed variables. The relationships between the BCSQ-36 and the other constructs were analysed using Spearman’s r and multiple linear regression models. Results The structure of the BCSQ-36 fit the data well, with adequate CFA indices for all the burnout subtypes. Reliability was adequate for all the scales and sub-scales (R≥0.75). Self-judgement was the self-compassion factor that explained the frenetic subtype (Beta = 0.36; p<0.001); isolation explained the underchallenged (Beta = 0.16; p = 0.010); and over-identification the worn-out (Beta = 0.25; p = 0.001). Other significant associations were observed between the different burnout subtypes and the dimensions of the MBI-GS, UWES and PANAS. Conclusions The typological definition of burnout through the BCSQ-36 showed good structure and appropriate internal consistence in Spanish primary healthcare professionals. The negative self-compassion dimensions seem to play a relevant role in explaining the burnout profiles in this population, and they should be considered when designing specific treatments and interventions tailored to the specific vulnerability of each subtype. PMID:27310426

Discovery of isonicotinamide derived beta-secretase inhibitors: in vivo reduction of beta-amyloid.

PubMed

Stanton, Matthew G; Stauffer, Shaun R; Gregro, Alison R; Steinbeiser, Melissa; Nantermet, Philippe; Sankaranarayanan, Sethu; Price, Eric A; Wu, Guoxin; Crouthamel, Ming-Chih; Ellis, Joan; Lai, Ming-Tain; Espeseth, Amy S; Shi, Xiao-Ping; Jin, Lixia; Colussi, Dennis; Pietrak, Beth; Huang, Qian; Xu, Min; Simon, Adam J; Graham, Samuel L; Vacca, Joseph P; Selnick, Harold

2007-07-26

beta-Secretase inhibition offers an exciting opportunity for therapeutic intervention in the progression of Alzheimer's disease. A series of isonicotinamides derived from traditional aspartyl protease transition state isostere inhibitors has been optimized to yield low nanomolar inhibitors with sufficient penetration across the blood-brain barrier to demonstrate beta-amyloid lowering in a murine model.

Deep Learning with Hierarchical Convolutional Factor Analysis

PubMed Central

Chen, Bo; Polatkan, Gungor; Sapiro, Guillermo; Blei, David; Dunson, David; Carin, Lawrence

2013-01-01

Unsupervised multi-layered (“deep”) models are considered for general data, with a particular focus on imagery. The model is represented using a hierarchical convolutional factor-analysis construction, with sparse factor loadings and scores. The computation of layer-dependent model parameters is implemented within a Bayesian setting, employing a Gibbs sampler and variational Bayesian (VB) analysis, that explicitly exploit the convolutional nature of the expansion. In order to address large-scale and streaming data, an online version of VB is also developed. The number of basis functions or dictionary elements at each layer is inferred from the data, based on a beta-Bernoulli implementation of the Indian buffet process. Example results are presented for several image-processing applications, with comparisons to related models in the literature. PMID:23787342

Assessment of nickel titanium and beta titanium corrosion resistance behavior in fluoride and chloride environments.

PubMed

Kassab, Elisa J; Gomes, José Ponciano

2013-09-01

To assess the influence of fluoride concentration on the corrosion behavior of nickel titanium (NiTi) superelastic wire and to compare the corrosion resistance of NiTi with that of beta titanium alloy in physiological solution with and without addition of fluoride. NiTi corrosion resistance was investigated through electrochemical impedance spectroscopy and anodic polarization in sodium chloride (NaCl 0.15 M) with and without addition of 0.02 M sodium fluoride (NaF), and the results were compared with those associated with beta titanium. The influence of fluoride concentration on NiTi corrosion behavior was assessed in NaCl (0.15 M) with and without 0.02, 0.04, 0.05, 0.07, and 0.12 M NaF solution. Galvanic corrosion between NiTi and beta titanium were investigated. All samples were characterized by scanning electron microscopy. Polarization resistance decreased when NaF concentration was increased, and, depending on NaF concentration, NiTi can suffer localized or generalized corrosion. In NaCl solution with 0.02 M NaF, NiTi suffer localized corrosion, while beta titanium alloys remained passive. Current values near zero were observed by galvanic coupling of NiTi and beta titanium. There is a decrease in NiTi corrosion resistance in the presence of fluoride. The corrosion behavior of NiTi alloy depends on fluoride concentration. When 0.02 and 0.04 M of NaF were added to the NaCl solution, NiTi presented localized corrosion. When NaF concentration increased to 0.05, 0.07, and 0.12 M, the alloy presented general corrosion. NiTi corrosion resistance behavior is lower than that of beta titanium. Galvanic coupling of these alloys does not increase corrosion rates.

Protein-induced Photophysical Changes to the Amyloid Indicator Dye Thioflavin T

DOE Office of Scientific and Technical Information (OSTI.GOV)

L Wolfe; M Calabrese; A Nath

2011-12-31

The small molecule thioflavin T (ThT) is a defining probe for the identification and mechanistic study of amyloid fiber formation. As such, ThT is fundamental to investigations of serious diseases such as Alzheimer's disease, Parkinson disease, and type II diabetes. For each disease, a different protein undergoes conformational conversion to a {beta}-sheet rich fiber. The fluorescence of ThT exhibits an increase in quantum yield upon binding these fibers. Despite its widespread use, the structural basis for binding specificity and for the changes to the photophysical properties of ThT remain poorly understood. Here, we report the co-crystal structures of ThT withmore » two alternative states of {beta}-2 microglobulin ({beta}2m); one monomeric, the other an amyloid-like oligomer. In the latter, the dye intercalates between {beta}-sheets orthogonal to the {beta}-strands. Importantly, the fluorophore is bound in such a manner that a photophysically relevant torsion is limited to a range of angles generally associated with low, not high, quantum yield. Quantum mechanical assessment of the fluorophore shows the electronic distribution to be strongly stabilized by aromatic interactions with the protein. Monomeric {beta}2m gives little increase in ThT fluorescence despite showing three fluorophores, at two binding sites, in configurations generally associated with high quantum yield. Our efforts fundamentally extend existing understanding about the origins of amyloid-induced photophysical changes. Specifically, the {beta}-sheet interface that characterizes amyloid acts both sterically and electronically to stabilize the fluorophore's ground state electronic distribution. By preventing the fluorophore from adopting its preferred excited state configuration, nonradiative relaxation pathways are minimized and quantum yield is increased.« less

Protein-induced photophysical changes to the amyloid indicator dye thioflavin T

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wolfe, Leslie S.; Calabrese, Matthew F.; Nath, Abhinav

2010-10-04

The small molecule thioflavin T (ThT) is a defining probe for the identification and mechanistic study of amyloid fiber formation. As such, ThT is fundamental to investigations of serious diseases such as Alzheimer's disease, Parkinson disease, and type II diabetes. For each disease, a different protein undergoes conformational conversion to a {beta}-sheet rich fiber. The fluorescence of ThT exhibits an increase in quantum yield upon binding these fibers. Despite its widespread use, the structural basis for binding specificity and for the changes to the photophysical properties of ThT remain poorly understood. Here, we report the co-crystal structures of ThT withmore » two alternative states of {beta}-2 microglobulin ({beta}2m); one monomeric, the other an amyloid-like oligomer. In the latter, the dye intercalates between {beta}-sheets orthogonal to the {beta}-strands. Importantly, the fluorophore is bound in such a manner that a photophysically relevant torsion is limited to a range of angles generally associated with low, not high, quantum yield. Quantum mechanical assessment of the fluorophore shows the electronic distribution to be strongly stabilized by aromatic interactions with the protein. Monomeric {beta}2m gives little increase in ThT fluorescence despite showing three fluorophores, at two binding sites, in configurations generally associated with high quantum yield. Our efforts fundamentally extend existing understanding about the origins of amyloid-induced photophysical changes. Specifically, the {beta}-sheet interface that characterizes amyloid acts both sterically and electronically to stabilize the fluorophore's ground state electronic distribution. By preventing the fluorophore from adopting its preferred excited state configuration, nonradiative relaxation pathways are minimized and quantum yield is increased.« less

A comparative analysis reveals weak relationships between ecological factors and beta diversity of stream insect metacommunities at two spatial levels.

PubMed

Heino, Jani; Melo, Adriano S; Bini, Luis Mauricio; Altermatt, Florian; Al-Shami, Salman A; Angeler, David G; Bonada, Núria; Brand, Cecilia; Callisto, Marcos; Cottenie, Karl; Dangles, Olivier; Dudgeon, David; Encalada, Andrea; Göthe, Emma; Grönroos, Mira; Hamada, Neusa; Jacobsen, Dean; Landeiro, Victor L; Ligeiro, Raphael; Martins, Renato T; Miserendino, María Laura; Md Rawi, Che Salmah; Rodrigues, Marciel E; Roque, Fabio de Oliveira; Sandin, Leonard; Schmera, Denes; Sgarbi, Luciano F; Simaika, John P; Siqueira, Tadeu; Thompson, Ross M; Townsend, Colin R

2015-03-01

The hypotheses that beta diversity should increase with decreasing latitude and increase with spatial extent of a region have rarely been tested based on a comparative analysis of multiple datasets, and no such study has focused on stream insects. We first assessed how well variability in beta diversity of stream insect metacommunities is predicted by insect group, latitude, spatial extent, altitudinal range, and dataset properties across multiple drainage basins throughout the world. Second, we assessed the relative roles of environmental and spatial factors in driving variation in assemblage composition within each drainage basin. Our analyses were based on a dataset of 95 stream insect metacommunities from 31 drainage basins distributed around the world. We used dissimilarity-based indices to quantify beta diversity for each metacommunity and, subsequently, regressed beta diversity on insect group, latitude, spatial extent, altitudinal range, and dataset properties (e.g., number of sites and percentage of presences). Within each metacommunity, we used a combination of spatial eigenfunction analyses and partial redundancy analysis to partition variation in assemblage structure into environmental, shared, spatial, and unexplained fractions. We found that dataset properties were more important predictors of beta diversity than ecological and geographical factors across multiple drainage basins. In the within-basin analyses, environmental and spatial variables were generally poor predictors of variation in assemblage composition. Our results revealed deviation from general biodiversity patterns because beta diversity did not show the expected decreasing trend with latitude. Our results also call for reconsideration of just how predictable stream assemblages are along ecological gradients, with implications for environmental assessment and conservation decisions. Our findings may also be applicable to other dynamic systems where predictability is low.

Intracerebral beta-endorphin, met-enkephalin and morphine: kindling of seizures and handling-induced potentiation of epileptiform effects.

PubMed

Cain, D P; Corcoran, M E

1984-06-18

The effects of repeated infusion of small, initially subconvulsive amounts of beta-endorphin, met-enkephalin or morphine sulfate into the amygdala and hippocampus were investigated. beta-endorphin and met-enkephalin evoked epileptiform spiking when infused into the posterior amygdala or ventral hippocampus. Morphine evoked epileptiform spiking when infused into the anterior amygdala. Naloxone blocked or terminated the spiking. Repetition of the infusions led to the gradual development of bilateral generalized convulsions by beta-endorphin and met-enkephalin and to the development of tolerance to morphine. An unexpected observation was that handling, immobilization or conspecific threat potentiated the epileptiform effects of beta-endorphin and morphine in many cases. These results suggest that endogenous opiate mechanisms might play a role in convulsive seizures and that stressful stimuli can exacerbate opiate seizures.

Sex hormones and quantitative ultrasound parameters at the heel in men and women from the general population.

PubMed

Pätzug, Konrad; Friedrich, Nele; Kische, Hanna; Hannemann, Anke; Völzke, Henry; Nauck, Matthias; Keevil, Brian G; Haring, Robin

2017-12-01

The present study investigates potential associations between liquid chromatography-mass spectrometry (LC-MS) measured sex hormones, dehydroepiandrosterone sulphate, sex hormone-binding globulin (SHBG) and bone ultrasound parameters at the heel in men and women from the general population. Data from 502 women and 425 men from the population-based Study of Health in Pomerania (SHIP-TREND) were used. Cross-sectional associations of sex hormones including testosterone (TT), calculated free testosterone (FT), dehydroepiandrosterone sulphate (DHEAS), androstenedione (ASD), estrone (E1) and SHBG with quantitative ultrasound (QUS) parameters at the heel, including broadband ultrasound attenuation (BUA), speed of sound (SOS) and stiffness index (SI) were examined by analysis of variance (ANOVA) and multivariable quantile regression models. Multivariable regression analysis showed a sex-specific inverse association of DHEAS with SI in men (Beta per SI unit = - 3.08, standard error (SE) = 0.88), but not in women (Beta = - 0.01, SE = 2.09). Furthermore, FT was positively associated with BUA in men (Beta per BUA unit = 29.0, SE = 10.1). None of the other sex hormones (ASD, E1) or SHBG was associated with QUS parameters after multivariable adjustment. This cross-sectional population-based study revealed independent associations of DHEAS and FT with QUS parameters in men, suggesting a potential influence on male bone metabolism. The predictive role of DHEAS and FT as a marker for osteoporosis in men warrants further investigation in clinical trials and large-scale observational studies.

Discovery of novel acetanilide derivatives as potent and selective beta3-adrenergic receptor agonists.

PubMed

Maruyama, Tatsuya; Onda, Kenichi; Hayakawa, Masahiko; Matsui, Tetsuo; Takasu, Toshiyuki; Ohta, Mitsuaki

2009-06-01

In the search for potent and selective human beta3-adrenergic receptor (AR) agonists as potential drugs for the treatment of obesity and noninsulin-dependent (type II) diabetes, a novel series of acetanilide-based analogues were prepared and their biological activities were evaluated at the human beta3-, beta2-, and beta1-ARs. Among these compounds, 2-pyridylacetanilide (2f), pyrimidin-2-ylacetanilide (2u), and pyrazin-2-ylacetanilide (2v) derivatives exhibited potent agonistic activity at the beta3-AR with functional selectivity over the beta1- and beta2-ARs. In particular, compound 2u was found to be the most potent and selective beta3-AR agonist with an EC(50) value of 0.11 microM and no agonistic activity for either the beta1- or beta2-AR. In addition, 2f, 2u, and 2v showed significant hypoglycemic activity in a rodent diabetic model.

Peginterferon Beta-1a Shows Antitumor Activity as a Single Agent and Enhances Efficacy of Standard of Care Cancer Therapeutics in Human Melanoma, Breast, Renal, and Colon Xenograft Models.

PubMed

Boccia, Antonio; Virata, Cyrus; Lindner, Daniel; English, Nicki; Pathan, Nuzhat; Brickelmaier, Margot; Hu, Xiao; Gardner, Jennifer L; Peng, Liaomin; Wang, Xinzhong; Zhang, Xiamei; Yang, Lu; Perron, Keli; Yco, Grace; Kelly, Rebecca; Gamez, James; Scripps, Thomas; Bennett, Donald; Joseph, Ingrid B; Baker, Darren P

2017-01-01

Because of its tumor-suppressive effect, interferon-based therapy has been used for the treatment of melanoma. However, limited data are available regarding the antitumor effects of pegylated interferons, either alone or in combination with approved anticancer drugs. We report that treatment of human WM-266-4 melanoma cells with peginterferon beta-1a induced apoptotic markers. Additionally, peginterferon beta-1a significantly inhibited the growth of human SK-MEL-1, A-375, and WM-266-4 melanoma xenografts established in immunocompromised mice. Peginterferon beta-1a regressed large, established WM-266-4 xenografts in nude mice. Treatment of SK-MEL-1 tumor-bearing mice with a combination of peginterferon beta-1a and the MEK inhibitor PD325901 ((R)-N-(2,3-dihydroxypropoxy)-3,4-difluoro-2-(2-fluoro-4-iodophenylamino)benzamide) significantly improved tumor growth inhibition compared with either agent alone. Examination of the antitumor activity of peginterferon beta-1a in combination with approved anticancer drugs in breast and renal carcinomas revealed improved antitumor activity in these preclinical xenograft models, as did the combination of peginterferon beta-1a and bevacizumab in a colon carcinoma xenograft model.

Simultaneous determination of specific alpha and beta emitters by LSC-PLS in water samples.

PubMed

Fons-Castells, J; Tent-Petrus, J; Llauradó, M

2017-01-01

Liquid scintillation counting (LSC) is a commonly used technique for the determination of alpha and beta emitters. However, LSC has poor resolution and the continuous spectra for beta emitters hinder the simultaneous determination of several alpha and beta emitters from the same spectrum. In this paper, the feasibility of multivariate calibration by partial least squares (PLS) models for the determination of several alpha ( nat U, 241 Am and 226 Ra) and beta emitters ( 40 K, 60 Co, 90 Sr/ 90 Y, 134 Cs and 137 Cs) in water samples is reported. A set of alpha and beta spectra from radionuclide calibration standards were used to construct three PLS models. Experimentally mixed radionuclides and intercomparision materials were used to validate the models. The results had a maximum relative bias of 25% when all the radionuclides in the sample were included in the calibration set; otherwise the relative bias was over 100% for some radionuclides. The results obtained show that LSC-PLS is a useful approach for the simultaneous determination of alpha and beta emitters in multi-radionuclide samples. However, to obtain useful results, it is important to include all the radionuclides expected in the studied scenario in the calibration set. Copyright © 2016 Elsevier Ltd. All rights reserved.

[Effect of ginsenoside Rb1 on cerebral infarction volume and IL-1 beta in the brain tissue and sera of focal cerebral ischemia/reperfusion injury model rats].

PubMed

Liu, Jun-Wei; Ren, Ye-Long; Liu, Xu-Ling; Xia, Hong-Lian; Zhang, Hui-Ling; Jin, Shen-Hui; Dai, Qin-Xue; Wang, Jun-Lu

2013-12-01

To investigate the effect of ginsenoside Rb1 on cerebral infarction volume as well as IL-1 beta in the brain tissue and sera of focal cerebral ischemia/reperfusion (I/R) injury model rats. The I/R rat model was established by using thread according to Zea-Longa. SD rats were randomly divided into five groups, i.e., the sham-operation group, the model group, the low dose ginsenoside Rb1 (20 mg/kg) group, the medium dose ginsenoside Rb1 group (40 mg/kg), and the high dose ginsenoside Rb1 group (80 mg/kg), 12 in each group. Rats in the sham-operation group only received middle cerebral artery occlusion (MCAO) but without thread insertion. The MCAO model was prepared in the rest 4 groups, followed by MCAO2 h later. Ginsenoside Rb1 at each dose was peritoneally administrated to rats in corresponding groups immediately after cerebral ischemia. Equal volume of normal saline was administered to rats in the sham-operation group. Rats' cerebral infarction volume, integrals of neurologic defect degree, expression of IL-1 beta content in the brain tissue and sera were observed 24 h after 2-h cerebral I/R. In the model group, integrals of neurologic defect degree were improved (P < 0.01), IL-1 beta positive cells in the brain tissue increased and serum IL-1 beta content elevated (P < 0.05), when compared with the sham-operation group. In comparison of the model group, integrals of neurologic defect degree were lowered in the medium dose and high dose ginsenoside Rb1 groups (P < 0.05, P < 0.01). The cerebral infarction volume was all shrunken in each ginsenoside Rb1 group, IL-1 beta positive cells in the brain tissue decreased, and IL-1 beta content in serum reduced (P < 0.01, P < 0.05). Compared with the low dose ginsenoside Rb1 group, integrals of neurologic defect degree decreased, the cerebral infarction volume shrunken, and IL-1 beta content in serum reduced in the high dose ginsenoside Rb1 group (P < 0.01, P < 0.05). Ginsenoside Rb1 (20, 40, 80 mg/kg) might effectively release local cerebral ischemia by down-regulating the IL-1 beta expression.

Bone sialoprotein mediates the tumor cell-targeted prometastatic activity of transforming growth factor beta in a mouse model of breast cancer.

PubMed

Nam, Jeong-Seok; Suchar, Adam M; Kang, Mi-Jin; Stuelten, Christina H; Tang, Binwu; Michalowska, Aleksandra M; Fisher, Larry W; Fedarko, Neal S; Jain, Alka; Pinkas, Jan; Lonning, Scott; Wakefield, Lalage M

2006-06-15

Transforming growth factor betas (TGF-beta) play a dual role in carcinogenesis, functioning as tumor suppressors early in the process, and then switching to act as prometastatic factors in late-stage disease. We have previously shown that high molecular weight TGF-beta antagonists can suppress metastasis without the predicted toxicities. To address the underlying mechanisms, we have used the 4T1 syngeneic mouse model of metastatic breast cancer. Treatment of mice with a monoclonal anti-TGF-beta antibody (1D11) significantly suppressed metastasis of 4T1 cells to the lungs. When metastatic 4T1 cells were recovered from lungs of 1D11-treated and control mice, the most differentially expressed gene was found to be bone sialoprotein (Bsp). Immunostaining confirmed the loss of Bsp protein in 1D11-treated lung metastases, and TGF-beta was shown to regulate and correlate with Bsp expression in vitro. Functionally, knockdown of Bsp in 4T1 cells reduced the ability of TGF-beta to induce local collagen degradation and invasion in vitro, and treatment with recombinant Bsp protected 4T1 cells from complement-mediated lysis. Finally, suppression of Bsp in 4T1 cells reduced metastasis in vivo. We conclude that Bsp is a plausible mediator of at least some of the tumor cell-targeted prometastatic activity of TGF-beta in this model and that Bsp expression in metastases can be successfully suppressed by systemic treatment with anti-TGF-beta antibodies.

Factors associated with blood oxygen partial pressure and carbon dioxide partial pressure regulation during respiratory extracorporeal membrane oxygenation support: data from a swine model.

PubMed

Park, Marcelo; Mendes, Pedro Vitale; Costa, Eduardo Leite Vieira; Barbosa, Edzangela Vasconcelos Santos; Hirota, Adriana Sayuri; Azevedo, Luciano Cesar Pontes

2016-01-01

The aim of this study was to explore the factors associated with blood oxygen partial pressure and carbon dioxide partial pressure. The factors associated with oxygen - and carbon dioxide regulation were investigated in an apneic pig model under veno-venous extracorporeal membrane oxygenation support. A predefined sequence of blood and sweep flows was tested. Oxygenation was mainly associated with extracorporeal membrane oxygenation blood flow (beta coefficient = 0.036mmHg/mL/min), cardiac output (beta coefficient = -11.970mmHg/L/min) and pulmonary shunting (beta coefficient = -0.232mmHg/%). Furthermore, the initial oxygen partial pressure and carbon dioxide partial pressure measurements were also associated with oxygenation, with beta coefficients of 0.160 and 0.442mmHg/mmHg, respectively. Carbon dioxide partial pressure was associated with cardiac output (beta coefficient = 3.578mmHg/L/min), sweep gas flow (beta coefficient = -2.635mmHg/L/min), temperature (beta coefficient = 4.514mmHg/ºC), initial pH (beta coefficient = -66.065mmHg/0.01 unit) and hemoglobin (beta coefficient = 6.635mmHg/g/dL). In conclusion, elevations in blood and sweep gas flows in an apneic veno-venous extracorporeal membrane oxygenation model resulted in an increase in oxygen partial pressure and a reduction in carbon dioxide partial pressure 2, respectively. Furthermore, without the possibility of causal inference, oxygen partial pressure was negatively associated with pulmonary shunting and cardiac output, and carbon dioxide partial pressure was positively associated with cardiac output, core temperature and initial hemoglobin.

Amino acid sequence requirements at residues 69 and 238 for the SME-1 beta-lactamase to confer resistance to beta-lactam antibiotics.

PubMed

Majiduddin, Fahd K; Palzkill, Timothy

2003-03-01

Carbapenem antibiotics have been used to counteract resistant strains of bacteria harboring beta-lactamases and extended-spectrum beta-lactamases. Four enzymes from the class A group of beta-lactamases, NMC-A, IMI-1, SME-1, and KPC-1, efficiently hydrolyze carbapenem antibiotics. Sequence comparisons and structural information indicate that cysteines at amino acid residues 69 and 238, which are conserved in all four of these enzymes, form a disulfide bond that is unique to these beta-lactamases. To test whether this disulfide bond is required for catalytic activity, the codons for residues Cys69 and Cys238 were randomized individually and simultaneously by PCR-based mutagenesis to create random replacement libraries for these positions. Mutants that were able to confer resistance to ampicillin, imipenem, or cefotaxime were selected from these libraries. The results indicate that positions Cys69 and Cys238 are critical for hydrolysis of all of the antibiotics tested, suggesting that the disulfide bond is generally required for this enzyme to catalyze the hydrolysis of beta-lactam antibiotics.

Neutrinoless double beta decay in type I+II seesaw models

NASA Astrophysics Data System (ADS)

Borah, Debasish; Dasgupta, Arnab

2015-11-01

We study neutrinoless double beta decay in left-right symmetric extension of the standard model with type I and type II seesaw origin of neutrino masses. Due to the enhanced gauge symmetry as well as extended scalar sector, there are several new physics sources of neutrinoless double beta decay in this model. Ignoring the left-right gauge boson mixing and heavy-light neutrino mixing, we first compute the contributions to neutrinoless double beta decay for type I and type II dominant seesaw separately and compare with the standard light neutrino contributions. We then repeat the exercise by considering the presence of both type I and type II seesaw, having non-negligible contributions to light neutrino masses and show the difference in results from individual seesaw cases. Assuming the new gauge bosons and scalars to be around a TeV, we constrain different parameters of the model including both heavy and light neutrino masses from the requirement of keeping the new physics contribution to neutrinoless double beta decay amplitude below the upper limit set by the GERDA experiment and also satisfying bounds from lepton flavor violation, cosmology and colliders.

Beta particle transport and its impact on betavoltaic battery modeling.

PubMed

Alam, Tariq R; Pierson, Mark A; Prelas, Mark A

2017-12-01

Simulation of beta particle transport from a Ni-63 radioisotope in silicon using the Monte Carlo N-Particle (MCNP) transport code for monoenergetic beta particle average energy, monoenergetic beta particle maximum energy, and the more precise full beta energy spectrum of Ni-63 were demonstrated. The beta particle penetration depth and the shape of the energy deposition varied significantly for different transport approaches. A penetration depth of 2.25±0.25µm with a peak in energy deposition was found when using a monoenergetic beta particle average energy and a depth of 14.25±0.25µm with an exponential decrease in energy deposition was found when using a full beta energy spectrum and a 0° angular variation. For a 90° angular variation, i.e. an isotropic source, the penetration depth was decreased to 12.75±0.25µm and the backscattering coefficient increased to 0.46 with 30.55% of the beta energy escaping when using a full beta energy spectrum. Similarly, for a 0° angular variation and an isotropic source, an overprediction in the short circuit current and open circuit voltage solved by a simplified drift-diffusion model was observed when compared to experimental results from the literature. A good agreement in the results was found when self-absorption and isotope dilution in the source was considered. The self-absorption effect was 15% for a Ni-63 source with an activity of 0.25mCi. This effect increased to about 28.5% for a higher source activity of 1mCi due to an increase in thickness of the Ni-63 source. Source thicknesses of approximately 0.1µm and 0.4µm for these Ni-63 activities predicted about 15% and 28.5% self-absorption in the source, respectively, using MCNP simulations with an isotropic source. The modeling assumptions with different beta particle energy inputs, junction depth of the semiconductor, backscattering of beta particles, an isotropic beta source, and self-absorption of the radioisotope have significant impacts in betavoltaic battery design. Copyright © 2017 Elsevier Ltd. All rights reserved.

Functional cloning of the proto-oncogene brain factor-1 (BF-1) as a Smad-binding antagonist of transforming growth factor-beta signaling.

PubMed

Rodriguez, C; Huang, L J; Son, J K; McKee, A; Xiao, Z; Lodish, H F

2001-08-10

Using the plasminogen activator inhibitor (PAI) promoter to drive the expression of a reporter gene (mouse CD2), we devised a system to clone negative regulators of the transforming growth factor-beta (TGF-beta) signaling pathway. We infected a TGF-beta-responsive cell line (MvLu1) with a retroviral cDNA library, selecting by fluorescence-activated cell sorter single cells displaying low PAI promoter activity in response to TGF-beta. Using this strategy we cloned the proto-oncogene brain factor-1 (BF-1). BF-1 represses the PAI promoter in part by associating with both unphosphorylated Smad3 (in the cytoplasm) and phosphorylated Smad3 (in the nucleus), thus preventing its binding to DNA. BF-1 also associates with Smad1, -2, and -4; the Smad MH2 domain binds to BF-1, and the C-terminal segment of BF-1 is uniquely and solely required for binding to Smads. Further, BF-1 represses another TGF-beta-induced promoter (p15), it up-regulates a TGF-beta-repressed promoter (Cyclin A), and it reverses the growth arrest caused by TGF-beta. Our results suggest that BF-1 is a general inhibitor of TGF-beta signaling and as such may play a key role during brain development.

High frequency capacitance-voltage characteristics of thermally grown SiO2 films on beta-SiC

NASA Technical Reports Server (NTRS)

Tang, S. M.; Berry, W. B.; Kwor, R.; Zeller, M. V.; Matus, L. G.

1990-01-01

Silicon dioxide films grown under dry and wet oxidation environment on beta-SiC films have been studied. The beta-SiC films had been heteroepitaxially grown on both on-axis and 2-deg off-axis (001) Si substrates. Capacitance-voltage and conductance-voltage characteristics of metal-oxide-semiconductor structures were measured in a frequency range of 10 kHz to 1 MHz. From these measurements, the interface trap density and the effective fixed oxide charge density were observed to be generally lower for off-axis samples.

The treatment of anxiety with beta-blocking drugs.

PubMed

Peet, M

1988-01-01

Evidence supporting the efficacy of beta blockers in anxiety is reviewed. Propranolol and oxprenolol are the most clearly established in efficacy. A placebo-controlled trial is described, in which propranolol and atenolol were both effective in the symptomatic treatment of generalized anxiety in patients who had been referred by their family doctors for specialist treatment. If initial psychological treatment for chronic anxiety is ineffective, and a drug is considered necessary, then a beta blocker or an antidepressant should be considered as first choice in preference to a benzodiazepine.

The role of large-scale eddies in the climate equilibrium. Part 2: Variable static stability

NASA Technical Reports Server (NTRS)

Zhou, Shuntai; Stone, Peter H.

1993-01-01

Lorenz's two-level model on a sphere is used to investigate how the results of Part 1 are modified when the interaction of the vertical eddy heat flux and static stability is included. In general, the climate state does not depend very much on whether or not this interaction is included, because the poleward eddy heat transport dominates the eddy forcing of mean temperature and wind fields. However, the climatic sensitivity is significantly affected. Compared to two-level model results with fixed static stability, the poleward eddy heat flux is less sensitive to the meridional temperature gradient and the gradient is more sensitive to the forcing. For example, the logarithmic derivative of the eddy flux with respect to the gradient has a slope that is reduced from approximately 15 on a beta-plane with fixed static stability and approximately 6 on a sphere with fixed static stability, to approximately 3 to 4 in the present model. This last result is more in line with analyses from observations. The present model also has a stronger baroclinic adjustment than that in Part 1, more like that in two-level beta-plane models with fixed static stability, that is, the midlatitude isentropic slope is very insensitive to the forcing, the diabatic heating, and the friction, unless the forcing is very weak.

Hinge residue I174 is critical for proper dNTP selection by DNA polymerase beta.

PubMed

Yamtich, Jen; Starcevic, Daniela; Lauper, Julia; Smith, Elenoe; Shi, Idina; Rangarajan, Sneha; Jaeger, Joachim; Sweasy, Joann B

2010-03-23

DNA polymerase beta (pol beta) is the key gap-filling polymerase in base excision repair, the DNA repair pathway responsible for repairing up to 20000 endogenous lesions per cell per day. Pol beta is also widely used as a model polymerase for structure and function studies, and several structural regions have been identified as being critical for the fidelity of the enzyme. One of these regions is the hydrophobic hinge, a network of hydrophobic residues located between the palm and fingers subdomains. Previous work by our lab has shown that hinge residues Y265, I260, and F272 are critical for polymerase fidelity by functioning in discrimination of the correct from incorrect dNTP during ground state binding. Our work aimed to elucidate the role of hinge residue I174 in polymerase fidelity. To study this residue, we conducted a genetic screen to identify mutants with a substitution at residue I174 that resulted in a mutator polymerase. We then chose the mutator mutant I174S for further study and found that it follows the same general kinetic pathway as and has an overall protein folding similar to that of wild-type (WT) pol beta. Using single-turnover kinetic analysis, we found that I174S exhibits decreased fidelity when inserting a nucleotide opposite a template base G, and this loss of fidelity is due primarily to a loss of discrimination during ground state dNTP binding. Molecular dynamics simulations show that mutation of residue I174 to serine results in an overall tightening of the hinge region, resulting in aberrant protein dynamics and fidelity. These results point to the hinge region as being critical in the maintenance of the proper geometry of the dNTP binding pocket.

Multifactorial inheritance with cultural transmission and assortative mating. II. a general model of combined polygenic and cultural inheritance.

PubMed Central

Cloninger, C R; Rice, J; Reich, T

1979-01-01

A general linear model of combined polygenic-cultural inheritance is described. The model allows for phenotypic assortative mating, common environment, maternal and paternal effects, and genic-cultural correlation. General formulae for phenotypic correlation between family members in extended pedigrees are given for both primary and secondary assortative mating. A FORTRAN program BETA, available upon request, is used to provide maximum likelihood estimates of the parameters from reported correlations. American data about IQ and Burks' culture index are analyzed. Both cultural and genetic components of phenotypic variance are observed to make significant and substantial contributions to familial resemblance in IQ. The correlation between the environments of DZ twins is found to equal that of singleton sibs, not that of MZ twins. Burks' culture index is found to be an imperfect measure of midparent IQ rather than an index of home environment as previously assumed. Conditions under which the parameters of the model may be uniquely and precisely estimated are discussed. Interpretation of variance components in the presence of assortative mating and genic-cultural covariance is reviewed. A conservative, but robust, approach to the use of environmental indices is described. PMID:453202

All of the human beta-type globin genes compete for LCR enhancer activity in embryonic erythroid cells of yeast artificial chromosome transgenic mice.

PubMed

Okamura, Eiichi; Matsuzaki, Hitomi; Campbell, Andrew D; Engel, James Douglas; Fukamizu, Akiyoshi; Tanimoto, Keiji

2009-12-01

In primitive erythroid cells of human beta-globin locus transgenic mice (TgM), the locus control region (LCR)-proximal epsilon- and gamma-globin genes are transcribed, whereas the distal delta- and beta-globin genes are silent. It is generally accepted that the beta-globin gene is competitively suppressed by gamma-globin gene expression at this developmental stage. Previously, however, we observed that epsilon-globin gene expression was severely attenuated when its distance from the LCR was extended, implying that beta-globin gene might also be silenced because of its great distance from the LCR. Here, to clarify the beta-globin gene silencing mechanism, we established TgM lines carrying either gamma- or epsilon- plus gamma-globin promoter deletions, without significantly altering the distance between the beta-globin gene and the LCR. Precocious expression of delta- and beta-globin genes was observed in primitive erythroid cells of mutant, but not wild-type TgM, which was most evident when both the epsilon and gamma promoters were deleted. Thus, we clearly demonstrated that the repression of the delta- and beta-globin genes in primitive erythroid cells is dominated by competitive silencing by the epsilon- and gamma-globin gene promoters, and that epsilon- and the other beta-like globin genes might be activated by two distinct mechanisms by the LCR.

Gross-alpha and gross-beta activities in airborne particulate samples. Analysis and prediction models.

PubMed

Dueñas, C; Fernández, M C; Carretero, J; Liger, E; Cañete, S

2001-04-01

Measurements of gross-alpha and gross-beta activities were made every week during the years 1992-1997 for airborne particulate samples collected using air filters at a clear site. The data are sufficiently numerous to allow the examination of variations in time and by these measurements to establish several features that should be important in understanding any trends of atmospheric radioactivity. Two models were used to predict the gross-alpha and gross-beta activities. A good agreement between the results of these models and the measurements was highlighted.

Effect of inhibition of glycogen synthase kinase-3 on cardiac hypertrophy during acute pressure overload.

PubMed

Tateishi, Atsushi; Matsushita, Masayuki; Asai, Tomohiro; Masuda, Zenichi; Kuriyama, Mitsuhito; Kanki, Kazushige; Ishino, Kozo; Kawada, Masaaki; Sano, Shunji; Matsui, Hideki

2010-06-01

A large number of diverse signaling molecules in cell and animal models participate in the stimulus-response pathway through which the hypertrophic growth of the myocardium is controlled. However, the mechanisms of signaling pathway including the influence of lithium, which is known as an inhibitor of glycogen synthase kinase-3beta, in pressure overload hypertrophy remain unclear. The aim of our study was to determine whether glycogen synthase kinase-3beta inhibition by lithium has acute effects on the myocyte growth mechanism in a pressure overload rat model. First, we created a rat model of acute pressure overload cardiac hypertrophy by abdominal aortic banding. Protein expression time courses for beta-catenin, glycogen synthase kinase-3beta, and phosphoserine9-glycogen synthase kinase-3beta were then examined. The rats were divided into four groups: normal rats with or without lithium administration and pressure-overloaded rats with or without lithium administration. Two days after surgery, Western blot analysis of beta-catenin, echo-cardiographic evaluation, left ventricular (LV) weight, and LV atrial natriuretic peptide mRNA levels were evaluated. We observed an increase in the level of glycogen synthase kinase-3beta phosphorylation on Ser 9. A significant enhancement of LV heart weight (P < 0.05) and interventricular septum and posterior wall thickness (P < 0.05) with pressure-overloaded hypertrophy in animals treated with lithium were also observed. Atrial natriuretic peptide mRNA levels were significantly increased with pressure overload hypertrophy in animals treated with lithium. We have shown in an animal model that inhibition of glycogen synthase kinase-3beta by lithium has an additive effect on pressure overload cardiac hypertrophy.

Respiratory effect of beta-blockers in people with asthma and cardiovascular disease: population-based nested case control study.

PubMed

Morales, Daniel R; Lipworth, Brian J; Donnan, Peter T; Jackson, Cathy; Guthrie, Bruce

2017-01-27

Cardiovascular disease (CVD) is a common comorbidity in people with asthma. However, safety concerns have caused heterogeneity in clinical guideline recommendations over the use of cardioselective beta-blockers in people with asthma and CVD, partly because risk in the general population has been poorly quantified. The aim of this study was to measure the risk of asthma exacerbations with beta-blockers prescribed to a general population with asthma and CVD. Linked data from the UK Clinical Practice Research Datalink was used to perform nested case-control studies among people with asthma and CVD matched on age, sex and calendar time. Adjusted incidence rate ratios (IRR) were calculated for the association between oral beta-blocker use and moderate asthma exacerbations (rescue oral steroids) or severe asthma exacerbations (hospitalisation or death) using conditional logistic regression. The cohort consisted of 35,502 people identified with active asthma and CVD, of which 14.1% and 1.2% were prescribed cardioselective and non-selective beta-blockers, respectively, during follow-up. Cardioselective beta-blocker use was not associated with a significantly increased risk of moderate or severe asthma exacerbations. Consistent results were obtained following sensitivity analyses and a self-controlled case series approach. In contrast, non-selective beta-blockers were associated with a significantly increased risk of moderate asthma exacerbations when initiated at low to moderate doses (IRR 5.16, 95% CI 1.83-14.54, P = 0.002), and both moderate and severe exacerbations when prescribed chronically at high dose (IRR 2.68, 95% CI 1.08-6.64, P = 0.033 and IRR 12.11, 95% CI 1.02-144.11, P = 0.048, respectively). Cardioselective beta-blockers prescribed to people with asthma and CVD were not associated with a significantly increased risk of moderate or severe asthma exacerbations and potentially could be used more widely when strongly indicated.

Early Stages of Microstructure and Texture Evolution during Beta Annealing of Ti-6Al-4V

NASA Astrophysics Data System (ADS)

Pilchak, A. L.; Sargent, G. A.; Semiatin, S. L.

2018-03-01

The early stages of microstructure evolution during annealing of Ti-6Al-4V in the beta phase field were established. For this purpose, a series of short-time heat treatments was performed using sheet samples that had a noticeable degree of alpha-phase microtexture in the as-received condition. Reconstruction of the beta-grain structure from electron-backscatter-diffraction measurements of the room-temperature alpha-phase texture revealed that microstructure evolution at short times was controlled not by general grain growth, but rather by nucleation-and-growth events analogous to discontinuous recrystallization. The nuclei comprised a small subset of beta grains that were highly misoriented relative to those comprising the principal texture component of the beta matrix. From a quantitative standpoint, the transformation kinetics were characterized by an Avrami exponent of approximately unity, thus suggestive of metadynamic recrystallization. The recrystallization process led to the weakening and eventual elimination of the initial beta texture through the growth of a population of highly misoriented grains.

Exploring species and site contributions to beta diversity in stream insect assemblages.

PubMed

Heino, Jani; Grönroos, Mira

2017-01-01

It was recently suggested that beta diversity can be partitioned into contributions of single sites to overall beta diversity (LCBD) or into contributions of individual species to overall beta diversity (SCBD). We explored the relationships of LCBD and SCBD to site and species characteristics, respectively, in stream insect assemblages. We found that LCBD was mostly explained by variation in species richness, with a negative relationship being detected. SCBD was strongly related to various species characteristics, such as occupancy, abundance, niche position and niche breadth, but was only weakly related to biological traits of species. In particular, occupancy and its quadratic terms showed a very strong unimodal relationship with SCBD, suggesting that intermediate species in terms of site occupancy contribute most to beta diversity. Our findings of unravelling the contributions of sites or species to overall beta diversity are of high importance to community ecology, conservation and bioassessment using stream insect assemblages, and may bear some overall generalities to be found in other organism groups.

Insight into multi-site mechanisms of glycosyl transfer in (1-->4)beta-D-glycans provided by the cereal mixed-linkage (1-->3),(1-->4)beta-D-glucan synthase.

PubMed

Buckeridge, M S; Vergara, C E; Carpita, N C

2001-08-01

Synthases of cellulose, chitin, hyaluronan, and all other polymers containing (1-->4)beta-linked glucosyl, mannosyl and xylosyl units have overcome a substrate orientation problem in catalysis because the (1-->4)beta-linkage requires that each of these sugar units be inverted nearly 180 degrees with respect to its neighbors. We and others have proposed that this problem is solved by two modes of glycosyl transfer within a single catalytic subunit to generate disaccharide units, which, when linked processively, maintain the proper orientation without rotation or re-orientation of the synthetic machinery in 3-dimensional space. A variant of the strict (1-->4)beta-D-linkage structure is the mixed-linkage (1-->3),(1-->4)beta-D-glucan, a growth-specific cell wall polysaccharide found in grasses and cereals. beta-Glucan is composed primarily of cellotriosyl and cellotetraosyl units linked by single (1-->3)beta-D-linkages. In reactions in vitro at high substrate concentration, a polymer composed of almost entirely cellotriosyl and cellopentosyl units is made. These results support a model in which three modes of glycosyl transfer occur within the synthase complex instead of just two. The generation of odd numbered units demands that they are connected by (1-->3)beta-linkages and not (1-->4)beta-. In this short review of beta-glucan synthesis in maize, we show how such a model not only provides simple mechanisms of synthesis for all (1-->4)beta-D-glycans but also explains how the synthesis of callose, or strictly (1-->3)beta-D-glucans, occurs upon loss of the multiple modes of glycosyl transfer to a single one.

Turbulent kinetic energy and a possible hierarchy of length scales in a generalization of the Navier-Stokes alpha theory.

PubMed

Fried, Eliot; Gurtin, Morton E

2007-05-01

We present a continuum-mechanical formulation and generalization of the Navier-Stokes alpha theory based on a general framework for fluid-dynamical theories with gradient dependencies. Our flow equation involves two additional problem-dependent length scales alpha and beta. The first of these scales enters the theory through the internal kinetic energy, per unit mass, alpha2|D|2, where D is the symmetric part of the gradient of the filtered velocity. The remaining scale is associated with a dissipative hyperstress which depends linearly on the gradient of the filtered vorticity. When alpha and beta are equal, our flow equation reduces to the Navier-Stokes alpha equation. In contrast to the original derivation of the Navier-Stokes alpha equation, which relies on Lagrangian averaging, our formulation delivers boundary conditions. For a confined flow, our boundary conditions involve an additional length scale l characteristic of the eddies found near walls. Based on a comparison with direct numerical simulations for fully developed turbulent flow in a rectangular channel of height 2h, we find that alphabeta approximately Re(0.470) and lh approximately Re(-0.772), where Re is the Reynolds number. The first result, which arises as a consequence of identifying the internal kinetic energy with the turbulent kinetic energy, indicates that the choice alpha=beta required to reduce our flow equation to the Navier-Stokes alpha equation is likely to be problematic. The second result evinces the classical scaling relation eta/L approximately Re(-3/4) for the ratio of the Kolmogorov microscale eta to the integral length scale L . The numerical data also suggests that l < or = beta . We are therefore led to conjecture a tentative hierarchy, l < or = beta < alpha , involving the three length scales entering our theory.

Inflammatory parameters in Caco-2 cells: effect of stimuli nature, concentration, combination and cell differentiation.

PubMed

Van De Walle, Jacqueline; Hendrickx, Aurélie; Romier, Béatrice; Larondelle, Yvan; Schneider, Yves-Jacques

2010-08-01

Enterocytes regulate gut maintenance and defence by secreting and responding to inflammatory mediators and by modulating the intestinal epithelial permeability. In order to develop an in vitro model of the acute phase of intestinal inflammation, Caco-2 cells were exposed to the inflammatory mediators IL-1beta, TNF-alpha, IFN-gamma and LPS, and the importance of several experimental parameters, i.e. cell differentiation, stimulus nature, concentration and combination on the inflammatory response was assessed by measuring the production of IL-6, IL-8, PGE-2 and NO and by evaluating the monolayer permeability. A maximal increase in IL-8, IL-6 and PGE-2 production and monolayer permeability was observed when using the cytokines simultaneously at their highest level, but this relied mainly on IL-1beta. The effects of TNF-alpha on IL-8 and IL-6 or NO production were stronger upon combination with IL-1beta or IFN-gamma, respectively, whereas cells were unaffected by the presence of LPS. Although NO production, induced by IFN-gamma-containing combinations, was observed only in differentiated cells, general inflammatory response was higher in proliferating cells. The use of a mixture of IL-1beta, TNF-alpha and IFN-gamma thus accurately mimics intestinal inflammatory processes, but cell differentiation and stimuli combination are important parameters to take into account for in vitro studies on intestinal inflammation. Copyright (c) 2010. Published by Elsevier Ltd.

Flexible work arrangements and work-family conflict after childbirth.

PubMed

Grice, Mira M; McGovern, Patricia M; Alexander, Bruce H

2008-10-01

Previous research has revealed that work-family conflict negatively influences women's health following childbirth. To examine if flexible work arrangements were associated with work-family conflict among women, 1 year after childbirth. Employed women, aged >or=18, were recruited while hospitalized for childbirth. Flexible work arrangements were measured at 6 months and work-family conflict was measured at 12 months. General linear models estimated the association between flexible work arrangements and work-family conflict. Of 1157 eligible participants, 522 were included in this analysis giving a 45% response rate. Compared to women who reported that taking time off was very hard, those who reported it was not too hard (beta = -0.80, SE = 0.36, P < 0.05) and not at all hard (beta = -1.08, SE = 0.35, P < 0.01) had lower average job spillover scores. There was no association between taking time off and home spillover. The ability to change hours was associated with greater home spillover (beta = 0.46, SE = 0.18, P < 0.05) but not with job spillover. The ability to take work home was associated with increased home spillover (beta = 0.35, SE = 0.14, P < 0.05) but not with job spillover. The ability to change work hours and the ability to take work home were associated with increased home spillover to work. The ability to take time off was associated with decreased job spillover to home. Additional research is needed to examine the intentional and unintentional consequences of flexible work arrangements.

Convenient QSAR model for predicting the complexation of structurally diverse compounds with beta-cyclodextrins.

PubMed

Pérez-Garrido, Alfonso; Morales Helguera, Aliuska; Abellán Guillén, Adela; Cordeiro, M Natália D S; Garrido Escudero, Amalio

2009-01-15

This paper reports a QSAR study for predicting the complexation of a large and heterogeneous variety of substances (233 organic compounds) with beta-cyclodextrins (beta-CDs). Several different theoretical molecular descriptors, calculated solely from the molecular structure of the compounds under investigation, and an efficient variable selection procedure, like the Genetic Algorithm, led to models with satisfactory global accuracy and predictivity. But the best-final QSAR model is based on Topological descriptors meanwhile offering a reasonable interpretation. This QSAR model was able to explain ca. 84% of the variance in the experimental activity, and displayed very good internal cross-validation statistics and predictivity on external data. It shows that the driving forces for CD complexation are mainly hydrophobic and steric (van der Waals) interactions. Thus, the results of our study provide a valuable tool for future screening and priority testing of beta-CDs guest molecules.

A simultaneous beta and coincidence-gamma imaging system for plant leaves

NASA Astrophysics Data System (ADS)

Ranjbar, Homayoon; Wen, Jie; Mathews, Aswin J.; Komarov, Sergey; Wang, Qiang; Li, Ke; O'Sullivan, Joseph A.; Tai, Yuan-Chuan

2016-05-01

Positron emitting isotopes, such as 11C, 13N, and 18F, can be used to label molecules. The tracers, such as 11CO2, are delivered to plants to study their biological processes, particularly metabolism and photosynthesis, which may contribute to the development of plants that have a higher yield of crops and biomass. Measurements and resulting images from PET scanners are not quantitative in young plant structures or in plant leaves due to poor positron annihilation in thin objects. To address this problem we have designed, assembled, modeled, and tested a nuclear imaging system (simultaneous beta-gamma imager). The imager can simultaneously detect positrons ({β+} ) and coincidence-gamma rays (γ). The imaging system employs two planar detectors; one is a regular gamma detector which has a LYSO crystal array, and the other is a phoswich detector which has an additional BC-404 plastic scintillator for beta detection. A forward model for positrons is proposed along with a joint image reconstruction formulation to utilize the beta and coincidence-gamma measurements for estimating radioactivity distribution in plant leaves. The joint reconstruction algorithm first reconstructs beta and gamma images independently to estimate the thickness component of the beta forward model and afterward jointly estimates the radioactivity distribution in the object. We have validated the physics model and reconstruction framework through a phantom imaging study and imaging a tomato leaf that has absorbed 11CO2. The results demonstrate that the simultaneously acquired beta and coincidence-gamma data, combined with our proposed joint reconstruction algorithm, improved the quantitative accuracy of estimating radioactivity distribution in thin objects such as leaves. We used the structural similarity (SSIM) index for comparing the leaf images from the simultaneous beta-gamma imager with the ground truth image. The jointly reconstructed images yield SSIM indices of 0.69 and 0.63, whereas the separately reconstructed beta alone and gamma alone images had indices of 0.33 and 0.52, respectively.

A simultaneous beta and coincidence-gamma imaging system for plant leaves.

PubMed

Ranjbar, Homayoon; Wen, Jie; Mathews, Aswin J; Komarov, Sergey; Wang, Qiang; Li, Ke; O'Sullivan, Joseph A; Tai, Yuan-Chuan

2016-05-07

Positron emitting isotopes, such as (11)C, (13)N, and (18)F, can be used to label molecules. The tracers, such as (11)CO2, are delivered to plants to study their biological processes, particularly metabolism and photosynthesis, which may contribute to the development of plants that have a higher yield of crops and biomass. Measurements and resulting images from PET scanners are not quantitative in young plant structures or in plant leaves due to poor positron annihilation in thin objects. To address this problem we have designed, assembled, modeled, and tested a nuclear imaging system (simultaneous beta-gamma imager). The imager can simultaneously detect positrons ([Formula: see text]) and coincidence-gamma rays (γ). The imaging system employs two planar detectors; one is a regular gamma detector which has a LYSO crystal array, and the other is a phoswich detector which has an additional BC-404 plastic scintillator for beta detection. A forward model for positrons is proposed along with a joint image reconstruction formulation to utilize the beta and coincidence-gamma measurements for estimating radioactivity distribution in plant leaves. The joint reconstruction algorithm first reconstructs beta and gamma images independently to estimate the thickness component of the beta forward model and afterward jointly estimates the radioactivity distribution in the object. We have validated the physics model and reconstruction framework through a phantom imaging study and imaging a tomato leaf that has absorbed (11)CO2. The results demonstrate that the simultaneously acquired beta and coincidence-gamma data, combined with our proposed joint reconstruction algorithm, improved the quantitative accuracy of estimating radioactivity distribution in thin objects such as leaves. We used the structural similarity (SSIM) index for comparing the leaf images from the simultaneous beta-gamma imager with the ground truth image. The jointly reconstructed images yield SSIM indices of 0.69 and 0.63, whereas the separately reconstructed beta alone and gamma alone images had indices of 0.33 and 0.52, respectively.

An assumed joint-Beta PDF approach for supersonic turbulent combustion

NASA Technical Reports Server (NTRS)

Baurle, R. A.; Alexopoulos, G. A.; Hassan, H. A.; Drummond, J. P.

1992-01-01

In a recent experiment, Cheng et al. (1991) used ultraviolet spontaneous vibrational Raman scattering and laser-induced predissociative fluorescence techniques for simultaneous measurements of temperature and concentrations of O2, H2, H2O, OH, and N2 (and their rms) in supersonic turbulent reacting shear layers. Because present computational techniques are not suited for prediction of all of the above measurements, a new approach has been developed and is being used to predict all relevant flow properties and their rms (where appropriate). The approach explores the use of a joint-Beta PDF for concentrations. It was found that the general expression of this PDF was impractical because of decoding problems resulting from determining the various parameters of the PDF. Thus, a special case of this general expression was considered. Calculations using this simplified version of the joint-Beta PDF were not consistent with the available data from the experiment.

Prolonged peritoneal gene expression using a helper-dependent adenovirus.

PubMed

Liu, Limin; Shi, Chang-Xin; Ghayur, Ayesha; Zhang, Claire; Su, Je Yen; Hoff, Catherine M; Margetts, Peter J

2009-01-01

Encapsulating peritoneal sclerosis (EPS) is a rare complication of peritoneal dialysis. The causes of EPS are not well defined and are likely multifactorial. A suitable animal model would facilitate research into the pathophysiology and treatment of EPS. We developed a helper-dependent adenovirus that expresses both green fluorescent protein (GFP) and active transforming growth factor-beta (TGF-beta1; HDAdTGF-beta1). Mice were administered HDAdTGF-beta1 via intraperitoneal injection and the response was compared with mice administered either first-generation adenovirus expressing TGF-beta1 (AdTGF-beta1) or control adenovirus (AdGFP). HDAdTGF-beta1-treated mice continued to express the GFP reporter transgene to day 74, the end of the observation period. Transgene expression lasted less than 28 days in the animals treated with first-generation adenoviruses. Animals treated with first-generation AdTGF-beta1 demonstrated submesothelial thickening and angiogenesis at day 7, with almost complete resolution by day 28. The HDAdTGF-beta1-treated mice demonstrated progressive peritoneal fibrosis with adhesion formation and encapsulation of bowels. Weight gain was significantly reduced in animals treated with HDAdTGF-beta1 compared to both the control-treated animals and the AdTGF-beta1-treated animals. Inflammation was not a major component of the fibroproliferative response. Peritoneal administration of a first-generation AdTGF-beta1 leads to transient gene expression, resulting in a resolving fibrotic response and histology similar to that seen in simple peritoneal sclerosis. Prolonged TGF-beta1 expression induced by the helper-dependent HDAdTGF-beta1 led to changes in peritoneal morphology resembling EPS. This suggests that TGF-beta1 may be a contributing factor in both simple peritoneal sclerosis and EPS. This model will be useful for elucidation of the mechanism of EPS and evaluation of potential treatment.

Discovery of nonsteroidal 17beta-hydroxysteroid dehydrogenase 1 inhibitors by pharmacophore-based screening of virtual compound libraries.

PubMed

Schuster, Daniela; Nashev, Lyubomir G; Kirchmair, Johannes; Laggner, Christian; Wolber, Gerhard; Langer, Thierry; Odermatt, Alex

2008-07-24

17Beta-hydroxysteroid dehydrogenase type 1 (17beta-HSD1) plays a pivotal role in the local synthesis of the most potent estrogen estradiol. Its expression is a prognostic marker for the outcome of patients with breast cancer and inhibition of 17beta-HSD1 is currently under consideration for breast cancer prevention and treatment. We aimed to identify nonsteroidal 17beta-HSD1 inhibitor scaffolds by virtual screening with pharmacophore models built from crystal structures containing steroidal compounds. The most promising model was validated by comparing predicted and experimentally determined inhibitory activities of several flavonoids. Subsequently, a virtual library of nonsteroidal compounds was screened against the 3D pharmacophore. Analysis of 14 selected compounds yielded four that inhibited the activity of human 17beta-HSD1 (IC 50 below 50 microM). Specificity assessment of identified 17beta-HSD1 inhibitors emphasized the importance of including related short-chain dehydrogenase/reductase (SDR) members to analyze off-target effects. Compound 29 displayed at least 10-fold selectivity over the related SDR enzymes tested.

The antifibrotic effects of TGF-{beta}1 siRNA on hepatic fibrosis in rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lang, Qing; Liu, Qi; Xu, Ning

2011-06-10

Highlights: {yields} We constructed CCL4 induced liver fibrosis model successfully. {yields} We proofed that the TGF-{beta}1 siRNA had a definite therapy effect to CCL4 induced liver fibrosis. {yields} The therapy effect of TGF-{beta}1 siRNA had dose-dependent. -- Abstract: Background/aims: Hepatic fibrosis results from the excessive secretion of matrix proteins by hepatic stellate cells (HSCs), which proliferate during fibrotic liver injury. Transforming growth factor (TGF)-{beta}1 is the dominant stimulus for extracellular matrix (ECM) production by stellate cells. Our study was designed to investigate the antifibrotic effects of using short interference RNA (siRNA) to target TGF-{beta}1 in hepatic fibrosis and its mechanismmore » in rats exposed to a high-fat diet and carbon tetrachloride (CCL4). Methods: A total of 40 healthy, male SD (Sprague-Dawley) rats were randomly divided into five even groups containing of eight rats each: normal group, model group, TGF-{beta}1 siRNA 0.125 mg/kg treatment group, TGF-{beta}1 siRNA 0.25 mg/kg treatment group and TGF-{beta}1 siRNA negative control group (0.25 mg/kg). CCL4 and a high-fat diet were used for 8 weeks to induce hepatic fibrosis. All the rats were then sacrificed to collect liver tissue samples. A portion of the liver samples were soaked in formalin for Hematoxylin-Eosin staining, classifying the degree of liver fibrosis, and detecting the expression of type I and III collagen and TGF-{beta}1; the remaining liver samples were stored in liquid nitrogen to be used for detecting TGF-{beta}1 by Western blotting and for measuring the mRNA expression of type I and III collagen and TGF-{beta}1 by quantitative real-time polymerase chain reaction. Results: Comparing the TGF-{beta}1 siRNA 0.25 mg/kg treatment group to the model group, the TGF-{beta}1 siRNA negative control group and the TGF-{beta}1 siRNA 0.125 mg/kg treatment group showed significantly reduced levels of pathological changes, protein expression and the mRNA expression of TGF-{beta}1, type I collagen and type III collagen (P < 0.01). Conclusions: Using siRNA to target TGF-{beta}1 can inhibit the expression of TGF-{beta}1 and attenuate rat hepatic fibrosis induced by a high-fat diet and CCL4. A possible mechanism is through the down-regulation of TGF-{beta}1 expression, which could inhibit HSC activation, as well as the proliferation and collagen production of collagen reducing, so that collagen deposition in the liver is reduced.« less

The effects of interferon-alpha/beta in a model of rat heart transplantation

NASA Technical Reports Server (NTRS)

Slater, A. D.; Klein, J. B.; Sonnenfeld, G.; Ogden, L. L. 2nd; Gray, L. A. Jr

1992-01-01

Interferons have multiple immunologic effects. One such effect is the activation of expression of cell surface antigens. Interferon alpha/beta enhance expression of class I but not class II histocompatibility antigens. Contradictory information has been published regarding the effect of interferon-alpha/beta administration in patients with kidney transplantation. In a model of rat heart transplantation we demonstrated that administration of interferon-alpha/beta accelerated rejection in a dose-dependent fashion in the absence of maintenance cyclosporine. Animals treated with maintenance cyclosporine had evidence of increased rejection at 20 days that was resolved completely at 45 days with cyclosporine alone.

Testing the gravitational instability hypothesis?

NASA Technical Reports Server (NTRS)

Babul, Arif; Weinberg, David H.; Dekel, Avishai; Ostriker, Jeremiah P.

1994-01-01

We challenge a widely accepted assumption of observational cosmology: that successful reconstruction of observed galaxy density fields from measured galaxy velocity fields (or vice versa), using the methods of gravitational instability theory, implies that the observed large-scale structures and large-scale flows were produced by the action of gravity. This assumption is false, in that there exist nongravitational theories that pass the reconstruction tests and gravitational theories with certain forms of biased galaxy formation that fail them. Gravitational instability theory predicts specific correlations between large-scale velocity and mass density fields, but the same correlations arise in any model where (a) structures in the galaxy distribution grow from homogeneous initial conditions in a way that satisfies the continuity equation, and (b) the present-day velocity field is irrotational and proportional to the time-averaged velocity field. We demonstrate these assertions using analytical arguments and N-body simulations. If large-scale structure is formed by gravitational instability, then the ratio of the galaxy density contrast to the divergence of the velocity field yields an estimate of the density parameter Omega (or, more generally, an estimate of beta identically equal to Omega(exp 0.6)/b, where b is an assumed constant of proportionality between galaxy and mass density fluctuations. In nongravitational scenarios, the values of Omega or beta estimated in this way may fail to represent the true cosmological values. However, even if nongravitational forces initiate and shape the growth of structure, gravitationally induced accelerations can dominate the velocity field at late times, long after the action of any nongravitational impulses. The estimated beta approaches the true value in such cases, and in our numerical simulations the estimated beta values are reasonably accurate for both gravitational and nongravitational models. Reconstruction tests that show correlations between galaxy density and velocity fields can rule out some physically interesting models of large-scale structure. In particular, successful reconstructions constrain the nature of any bias between the galaxy and mass distributions, since processes that modulate the efficiency of galaxy formation on large scales in a way that violates the continuity equation also produce a mismatch between the observed galaxy density and the density inferred from the peculiar velocity field. We obtain successful reconstructions for a gravitational model with peaks biasing, but we also show examples of gravitational and nongravitational models that fail reconstruction tests because of more complicated modulations of galaxy formation.

Kinetics and mechanisms of crystal growth inhibition of indomethacin by model precipitation inhibitors

NASA Astrophysics Data System (ADS)

Patel, Dhaval

Supersaturating Drug Delivery Systems (SDDS) could enhance oral bioavailability of poorly water soluble drugs (PWSD). Precipitation inhibitors (PIs) in SDDS could maintain supersaturation by inhibiting nucleation, crystal growth, or both. The mechanisms by which these effects are realized are generally unknown. The goal of this dissertation was to explore the mechanisms underpinning the effects of model PIs including hydroxypropyl beta-cyclodextrins (HP-beta-CD), hydroxypropyl methylcellulose (HPMC), and polyvinylpyrrolidone (PVP) on the crystal growth of indomethacin, a model PWSD. At high degrees of supersaturation (S), the crystal growth kinetics of indomethacin was bulk diffusion-controlled, which was attributed to a high energy form deposited on the seed crystals. At lower S, indomethacin growth kinetics was surface integration-controlled. The effect of HP-beta-CD at high S was successfully modeled using the reactive diffusion layer theory. The superior effects of PVP and HPMC as compared to HP-beta-CD at high S were attributed to a change in the rate limiting step from bulk diffusion to surface integration largely due to prevention of the high energy form formation. The effects of PIs at low S were attributed to significant retardation of the surface integration rate, a phenomenon that may reflect the adsorption of PIs onto the growing surface. PVP was selected to further understand the relationship between adsorption and crystal growth inhibition. The Langmuir adsorption isotherm model fit the adsorption isotherms of PVP and N-vinylpyrrolidone well. The affinity and extent of adsorption of PVP were significantly higher than those of N-vinylpyrrolidone, which was attributed to cooperative interactions between PVP and indomethacin. The extent of PVP adsorption on a weight-basis was greater for higher molecular weight PVP but less on a molar-basis indicating an increased percentage of loops and tails for higher molecular weight PVPs. PVP significantly inhibited indomethacin crystal growth at high S as compared to N-vinylpyrrolidone, which was attributed to a change in the growth mechanism resulting in a change in the rate limiting step from bulk diffusion to surface integration. Higher molecular weight PVPs were better inhibitors than lower molecular weight PVPs, which was attributed to a greater crystal growth barrier provided by a thicker adsorption layer.

Effects of intracerebroventricular administration of beta-amyloid on the dynamics of learning in purebred and mongrel rats.

PubMed

Stepanov, I I; Kuznetsova, N N; Klement'ev, B I; Sapronov, N S

2007-07-01

The effects of intracerebroventricular administration of the beta-amyloid peptide fragment Abeta(25-35) on the dynamics of the acquisition of a conditioned reflex in a Y maze were studied in Wistar and mongrel rats. The dynamics of decreases in the number of errors were assessed using an exponential mathematical model describing the transfer function of a first-order system in response to stepped inputs using non-linear regression analysis. This mathematical model provided a good approximation to the learning dynamics in inbred and mongrel mice. In Wistar rats, beta-amyloid impaired learning, with reduced memory between the first and second training sessions, but without complete blockade of learning. As a result, learning dynamics were no longer approximated by the mathematical model. At the same time, comparison of the number of errors in each training sessions between the control group of Wistar rats and the group given beta-amyloid showed no significant differences (Student's t test). This result demonstrates the advantage of regression analysis based on a mathematical model over the traditionally used statistical methods. In mongrel rats, the effect of beta-amyloid was limited to an a slowing of the process of learning as compared with control mongrel rats, with retention of the approximation by the mathematical model. It is suggested that mongrel animals have some kind of innate, genetically determined protective mechanism against the harmful effects of beta-amyloid.

Effect of dietary fiber on the activity of intestinal and fecal beta-glucuronidase activity during 1,2-dimethylhydrazine induced colon carcinogenesis.

PubMed

Manoj, G; Thampi, B S; Leelamma, S; Menon, P V

2001-01-01

The effects of fiber isolated from black gram (Phaseolus mungo) and coconut (Cocos nucifera) kernel on the metabolic activity of intestinal and fecal beta glucuronidase activity during 1,2-dimethylhydrazine induced colon carcinogenesis were studied. The results indicated that the inclusion of fiber from black gram and coconut kernel generally supported lower specific activities and less fecal output of beta-glucuronidase than did the fiber free diet. This study suggests that the fibers isolated from coconut or black gram may potentially play a role in preventing the formation of colon tumors induced by the carcinogen 1,2-dimethylhydrazine by reducing the activity of the intestinal as well as fecal beta-glucuronidase.

How disturbing are side effects of beta blockers.

PubMed

Besterman, E M

1983-07-01

Drug side effects are notoriously difficult to evaluate accurately. In this particular context there are further problems arising from the exclusion of many patients in some of the few published series of populations exposed to beta-blocking drugs. In some of these same series, placebo side effects appear to affect almost as many patients as the active drug. However, detailed breakdown of these side effects show significant differences in the actual complaints made by patients of each group. Apart from the well known major complications of beta-blocking drugs, the lesser but still disturbing ones to mention include generalized fatigue, muscle weakness, cold extremities, nightmares and impotence. A change of beta-blocking preparation or else lowering the dosage often ameliorates these problems.

An unconventional hypothesis of oxidation in Alzheimer's disease: intersections with excitotoxicity.

PubMed

Barger, Steven W

2004-09-01

There are two major lines of investigation from which a connection has been traditionally drawn between chemical oxidation and Alzheimer's disease. First, a major risk factor for AD is age, and oxidative stress has long been a component of general hypotheses about biological aging. The second line of reasoning is a corollary of the Amyloid Hypothesis, the assumption that the amyloid beta-peptide (A-beta) which comprises AD's pathognomic plaques is a key mediator of the neurodegeneration occurring in this disorder. Under many experimental conditions, A-beta has been shown to evoke oxidative damage to tissues, cells, and biomolecules; even the redox properties of the peptide itself have been hotly debated. These two modalities of conjecture intersect under the Inflammatory Hypothesis of AD, as inflammation produces oxidation, old age is associated with elevation in inflammatory events, and A-beta can further exacerbate such inflammatory reactions in brain cells. This review discusses these arguments about the pathogenesis of AD and how they might be generalized to other neurodegenerative conditions. But, additional speculation is offered in the form of an inclusionary mechanism that may be specific and novel enough to qualify as a third line of theory; namely, the possibility that inflammatory reactions in microglia--activated by A-beta or other factors among the "usual suspects"--initiate programmed oxidation that is converted to the neuron-specific stress of excitotoxicity.

Factors associated with blood oxygen partial pressure and carbon dioxide partial pressure regulation during respiratory extracorporeal membrane oxygenation support: data from a swine model

PubMed Central

Park, Marcelo; Mendes, Pedro Vitale; Costa, Eduardo Leite Vieira; Barbosa, Edzangela Vasconcelos Santos; Hirota, Adriana Sayuri; Azevedo, Luciano Cesar Pontes

2016-01-01

Objective The aim of this study was to explore the factors associated with blood oxygen partial pressure and carbon dioxide partial pressure. Methods The factors associated with oxygen - and carbon dioxide regulation were investigated in an apneic pig model under veno-venous extracorporeal membrane oxygenation support. A predefined sequence of blood and sweep flows was tested. Results Oxygenation was mainly associated with extracorporeal membrane oxygenation blood flow (beta coefficient = 0.036mmHg/mL/min), cardiac output (beta coefficient = -11.970mmHg/L/min) and pulmonary shunting (beta coefficient = -0.232mmHg/%). Furthermore, the initial oxygen partial pressure and carbon dioxide partial pressure measurements were also associated with oxygenation, with beta coefficients of 0.160 and 0.442mmHg/mmHg, respectively. Carbon dioxide partial pressure was associated with cardiac output (beta coefficient = 3.578mmHg/L/min), sweep gas flow (beta coefficient = -2.635mmHg/L/min), temperature (beta coefficient = 4.514mmHg/ºC), initial pH (beta coefficient = -66.065mmHg/0.01 unit) and hemoglobin (beta coefficient = 6.635mmHg/g/dL). Conclusion In conclusion, elevations in blood and sweep gas flows in an apneic veno-venous extracorporeal membrane oxygenation model resulted in an increase in oxygen partial pressure and a reduction in carbon dioxide partial pressure 2, respectively. Furthermore, without the possibility of causal inference, oxygen partial pressure was negatively associated with pulmonary shunting and cardiac output, and carbon dioxide partial pressure was positively associated with cardiac output, core temperature and initial hemoglobin. PMID:27096671

Deficiency of bone marrow beta3-integrin enhances non-functional neovascularization.

PubMed

Watson, Alan R; Pitchford, Simon C; Reynolds, Louise E; Direkze, Natalie; Brittan, Mairi; Alison, Malcolm R; Rankin, Sara; Wright, Nicholas A; Hodivala-Dilke, Kairbaan M

2010-03-01

beta3-Integrin is a cell surface adhesion and signalling molecule important in the regulation of tumour angiogenesis. Mice with a global deficiency in beta3-integrin show increased pathological angiogenesis, most likely due to increased vascular endothelial growth factor receptor 2 expression on beta3-null endothelial cells. Here we transplanted beta3-null bone marrow (BM) into wild-type (WT) mice to dissect the role of BM beta3-integrin deficiency in pathological angiogenesis. Mice transplanted with beta3-null bone marrow show significantly enhanced angiogenesis in subcutaneous B16F0 melanoma and Lewis lung carcinoma (LLC) cell models and in B16F0 melanoma lung metastasis when compared with tumours grown in mice transplanted with WT bone marrow. The effect of bone marrow beta3-integrin deficiency was also assessed in the RIPTAg mouse model of pancreatic tumour growth. Again, angiogenesis in mice lacking BM beta3-integrin was enhanced. However, tumour weight between the groups was not significantly altered, suggesting that the enhanced blood vessel density in the mice transplanted with beta3-null bone marrow was not functional. Indeed, we demonstrate that in mice transplanted with beta3-null bone marrow a significant proportion of tumour blood vessels are non-functional when compared with tumour blood vessels in WT-transplanted controls. Furthermore, beta3-null-transplanted mice showed an increased angiogenic response to VEGF in vivo when compared with WT-transplanted animals. BM beta3-integrin deficiency affects the mobilization of progenitor cells to the peripheral circulation. We show that VEGF-induced mobilization of endothelial progenitor cells is enhanced in mice transplanted with beta3-null bone marrow when compared with WT-transplanted controls, suggesting a possible mechanism underlying the increased blood vessel density seen in beta3-null-transplanted mice. In conclusion, although BM beta3-integrin is not required for pathological angiogenesis, our studies demonstrate a role for BM beta3-integrin in VEGF-induced mobilization of bone marrow-derived cells to the peripheral circulation and for the functionality of those vessels in which BM-derived cells become incorporated.

Riemannian geometry of Hamiltonian chaos: hints for a general theory.

PubMed

Cerruti-Sola, Monica; Ciraolo, Guido; Franzosi, Roberto; Pettini, Marco

2008-10-01

We aim at assessing the validity limits of some simplifying hypotheses that, within a Riemmannian geometric framework, have provided an explanation of the origin of Hamiltonian chaos and have made it possible to develop a method of analytically computing the largest Lyapunov exponent of Hamiltonian systems with many degrees of freedom. Therefore, a numerical hypotheses testing has been performed for the Fermi-Pasta-Ulam beta model and for a chain of coupled rotators. These models, for which analytic computations of the largest Lyapunov exponents have been carried out in the mentioned Riemannian geometric framework, appear as paradigmatic examples to unveil the reason why the main hypothesis of quasi-isotropy of the mechanical manifolds sometimes breaks down. The breakdown is expected whenever the topology of the mechanical manifolds is nontrivial. This is an important step forward in view of developing a geometric theory of Hamiltonian chaos of general validity.

Prevalence of shigellosis in the U.S.: consistency with dose-response information.

PubMed

Crockett, C S; Haas, C N; Fazil, A; Rose, J B; Gerba, C P

1996-06-01

Every year there are estimated 300000 cases of Shigella in the United States (Bennett et al., 1987, Am. J. Prev. Med. 3, 102-114). A beta-poisson model was fit to human dose-response information on pathogenic Shigella using the Maximum Likelihood Estimation technique (Haas, 1983, Am. J. Epidemiol. 118, 573-582). Pooled and separate data sets for the Shigella species were fit to the beta-Poisson model and 95% confidence limits and regions were calculated. Shigella dysentariae and Shigella flexneri confidence regions and limits overlapped with each other and with the pooled data set, suggesting that this model can describe Shigella in general. The pooled Shigella model as well as the upper and lower confidence limits of the three data sets showed average exposures based on the estimated U.S. caseload of pathogenic Shigella of 0.01 to 0.014 organisms (confidence limits 0.001-0.05) for a 7-day per annum period of exposure and ranges from 0.07 to 0.1 organisms (confidence limits 0.006-0.4). for a 1-day per annum period of exposure. The plausibility of the pooled dose-response model was then evaluated by comparison with two known cruise ship outbreaks. The pooled model estimated that the two outbreaks studied could have been due to ingestion of 344 (confidence limits 72-915) Shigella cells per meal and 10.5-12 (confidence limits 1-44) Shigella cells per glass of water by passengers.

Environmental and historical imprints on beta diversity: insights from variation in rates of species turnover along gradients

PubMed Central

Fitzpatrick, Matthew C.; Sanders, Nathan J.; Normand, Signe; Svenning, Jens-Christian; Ferrier, Simon; Gove, Aaron D.; Dunn, Robert R.

2013-01-01

A common approach for analysing geographical variation in biodiversity involves using linear models to determine the rate at which species similarity declines with geographical or environmental distance and comparing this rate among regions, taxa or communities. Implicit in this approach are weakly justified assumptions that the rate of species turnover remains constant along gradients and that this rate can therefore serve as a means to compare ecological systems. We use generalized dissimilarity modelling, a novel method that accommodates variation in rates of species turnover along gradients and between different gradients, to compare environmental and spatial controls on the floras of two regions with contrasting evolutionary and climatic histories: southwest Australia and northern Europe. We find stronger signals of climate history in the northern European flora and demonstrate that variation in rates of species turnover is persistent across regions, taxa and different gradients. Such variation may represent an important but often overlooked component of biodiversity that complicates comparisons of distance–decay relationships and underscores the importance of using methods that accommodate the curvilinear relationships expected when modelling beta diversity. Determining how rates of species turnover vary along and between gradients is relevant to understanding the sensitivity of ecological systems to environmental change. PMID:23926147

Atomic decomposition of the protein solvation free energy and its application to amyloid-beta protein in water

NASA Astrophysics Data System (ADS)

Chong, Song-Ho; Ham, Sihyun

2011-07-01

We report the development of an atomic decomposition method of the protein solvation free energy in water, which ascribes global change in the solvation free energy to local changes in protein conformation as well as in hydration structure. So far, empirical decomposition analyses based on simple continuum solvation models have prevailed in the study of protein-protein interactions, protein-ligand interactions, as well as in developing scoring functions for computer-aided drug design. However, the use of continuum solvation model suffers serious drawbacks since it yields the protein free energy landscape which is quite different from that of the explicit solvent model and since it does not properly account for the non-polar hydrophobic effects which play a crucial role in biological processes in water. Herein, we develop an exact and general decomposition method of the solvation free energy that overcomes these hindrances. We then apply this method to elucidate the molecular origin for the solvation free energy change upon the conformational transitions of 42-residue amyloid-beta protein (Aβ42) in water, whose aggregation has been implicated as a primary cause of Alzheimer's disease. We address why Aβ42 protein exhibits a great propensity to aggregate when transferred from organic phase to aqueous phase.

Microstructures and Grain Refinement of Additive-Manufactured Ti- xW Alloys

NASA Astrophysics Data System (ADS)

Mendoza, Michael Y.; Samimi, Peyman; Brice, David A.; Martin, Brian W.; Rolchigo, Matt R.; LeSar, Richard; Collins, Peter C.

2017-07-01

It is necessary to better understand the composition-processing-microstructure relationships that exist for materials produced by additive manufacturing. To this end, Laser Engineered Net Shaping (LENS™), a type of additive manufacturing, was used to produce a compositionally graded titanium binary model alloy system (Ti- xW specimen (0 ≤ x ≤ 30 wt pct), so that relationships could be made between composition, processing, and the prior beta grain size. Importantly, the thermophysical properties of the Ti- xW, specifically its supercooling parameter ( P) and growth restriction factor ( Q), are such that grain refinement is expected and was observed. The systematic, combinatorial study of this binary system provides an opportunity to assess the mechanisms by which grain refinement occurs in Ti-based alloys in general, and for additive manufacturing in particular. The operating mechanisms that govern the relationship between composition and grain size are interpreted using a model originally developed for aluminum and magnesium alloys and subsequently applied for titanium alloys. The prior beta grain factor observed and the interpretations of their correlations indicate that tungsten is a good grain refiner and such models are valid to explain the grain-refinement process. By extension, other binary elements or higher order alloy systems with similar thermophysical properties should exhibit similar grain refinement.

First demonstration of cerebrospinal fluid and plasma A beta lowering with oral administration of a beta-site amyloid precursor protein-cleaving enzyme 1 inhibitor in nonhuman primates.

PubMed

Sankaranarayanan, Sethu; Holahan, Marie A; Colussi, Dennis; Crouthamel, Ming-Chih; Devanarayan, Viswanath; Ellis, Joan; Espeseth, Amy; Gates, Adam T; Graham, Samuel L; Gregro, Allison R; Hazuda, Daria; Hochman, Jerome H; Holloway, Katharine; Jin, Lixia; Kahana, Jason; Lai, Ming-tain; Lineberger, Janet; McGaughey, Georgia; Moore, Keith P; Nantermet, Philippe; Pietrak, Beth; Price, Eric A; Rajapakse, Hemaka; Stauffer, Shaun; Steinbeiser, Melissa A; Seabrook, Guy; Selnick, Harold G; Shi, Xiao-Ping; Stanton, Matthew G; Swestock, John; Tugusheva, Katherine; Tyler, Keala X; Vacca, Joseph P; Wong, Jacky; Wu, Guoxin; Xu, Min; Cook, Jacquelynn J; Simon, Adam J

2009-01-01

beta-Site amyloid precursor protein (APP)-cleaving enzyme (BACE) 1 cleavage of amyloid precursor protein is an essential step in the generation of the potentially neurotoxic and amyloidogenic A beta 42 peptides in Alzheimer's disease. Although previous mouse studies have shown brain A beta lowering after BACE1 inhibition, extension of such studies to nonhuman primates or man was precluded by poor potency, brain penetration, and pharmacokinetics of available inhibitors. In this study, a novel tertiary carbinamine BACE1 inhibitor, tertiary carbinamine (TC)-1, was assessed in a unique cisterna magna ported rhesus monkey model, where the temporal dynamics of A beta in cerebrospinal fluid (CSF) and plasma could be evaluated. TC-1, a potent inhibitor (IC(50) approximately 0.4 nM), has excellent passive membrane permeability, low susceptibility to P-glycoprotein transport, and lowered brain A beta levels in a mouse model. Intravenous infusion of TC-1 led to a significant but transient lowering of CSF and plasma A beta levels in conscious rhesus monkeys because it underwent CYP3A4-mediated metabolism. Oral codosing of TC-1 with ritonavir, a potent CYP3A4 inhibitor, twice daily over 3.5 days in rhesus monkeys led to sustained plasma TC-1 exposure and a significant and sustained reduction in CSF sAPP beta, A beta 40, A beta 42, and plasma A beta 40 levels. CSF A beta 42 lowering showed an EC(50) of approximately 20 nM with respect to the CSF [TC-1] levels, demonstrating excellent concordance with its potency in a cell-based assay. These results demonstrate the first in vivo proof of concept of CSF A beta lowering after oral administration of a BACE1 inhibitor in a nonhuman primate.

Simultaneous measurements of the hydrogen airglow emissions of Lyman alpha, Lyman beta, and Balmer alpha.

NASA Technical Reports Server (NTRS)

Weller, C. S.; Meier, R. R.; Tinsley, B. A.

1971-01-01

Comparison of Lyman-alpha, 740- to 1050-A, and Balmer-alpha airglow measurements made at 134 deg solar-zenith angle on Oct. 13, 1969, with resonance-scattering models of solar radiation. Model comparison with Lyman-alpha data fixes the hydrogen column abundance over 215 km to 2 x 10 to the 13th per cu cm within a factor of 2. Differences between the Lyman-alpha model and data indicate a polar-equatorial departure from spherical symmetry in the hydrogen distribution. A Lyman-beta model based on the hydrogen distribution found to fit the Lyman-alpha data fits the spatial variation of the 740- to 1050-A data well from 100 to 130 km, but it does not fit the data well at higher altitudes; thus the presence of more rapidly absorbed shorter-wavelength radiation is indicated. This same resonance-scattering model yields Balmer-alpha intensities that result in good spatial agreement with the Balmer-alpha measurements, but a fivefold increase in the measured solar line center Lyman-beta flux is required (as required for the Lyman-beta measurement). The intensity ratio of Lyman-beta and Balmer-alpha at night is found to be a simple measure of the hydrogen optical depth if measurements with good accuracy can be made in the visible and ultraviolet spectrum.

17 beta-estradiol and tamoxifen upregulate estrogen receptor beta expression and control podocyte signaling pathways in a model of type 2 diabetes.

PubMed

Catanuto, Paola; Doublier, Sophie; Lupia, Enrico; Fornoni, Alessia; Berho, Mariana; Karl, Michael; Striker, Gary E; Xia, Xiaomei; Elliot, Sharon

2009-06-01

Diabetic nephropathy remains one of the most important causes of end-stage renal disease. This is particularly true for women from racial/ethnic minorities. Although administration of 17beta-estradiol to diabetic animals has been shown to reduce extracellular matrix deposition in glomeruli and mesangial cells, effects on podocytes are lacking. Given that podocyte injury has been implicated as a factor leading to the progression of proteinuria and diabetic nephropathy, we treated db/db mice, a model of type 2 diabetic glomerulosclerosis, with 17beta-estradiol or tamoxifen to determine whether these treatments reduce podocyte injury and decrease glomerulosclerosis. We found that albumin excretion, glomerular volume, and extracellular matrix accumulation were decreased in these mice compared to placebo treatment. Podocytes isolated from all treatment groups were immortalized and these cell lines were found to express the podocyte markers WT-1, nephrin, and the TRPC6 cation channel. Tamoxifen and 17beta-estradiol treatment decreased podocyte transforming growth factor-beta mRNA expression but increased that of the estrogen receptor subtype beta protein. 17beta-estradiol, but not tamoxifen, treatment decreased extracellular-regulated kinase phosphorylation. These data, combined with improved albumin excretion, reduced glomerular size, and decreased matrix accumulation, suggest that both 17beta-estradiol and tamoxifen may protect podocytes against injury and therefore ameliorate diabetic nephropathy.

The relationships between half-life (t1/2) and mean residence time (MRT) in the two-compartment open body model.

PubMed

Sobol, Eyal; Bialer, Meir

2004-05-01

In the one-compartment model following i.v. administration the mean residence time (MRT) of a drug is always greater than its half-life (t(1/2)). However, following i.v. administration, drug plasma concentration (C) versus time (t) is best described by a two-compartment model or a two exponential equation:C=Ae(-alpha t)+Be(-beta t), where A and B are concentration unit-coefficients and alpha and beta are exponential coefficients. The relationships between t(1/2) and MRT in the two-compartment model have not been explored and it is not clear whether in this model too MRT is always greater than t(1/2). In the current paper new equations have been developed that describe the relationships between the terminal t(1/2) (or t(1/2 beta)) and MRT in the two-compartment model following administration of i.v. bolus, i.v. infusion (zero order input) and oral administration (first order input). A critical value (CV) equals to the quotient of (1-ln2) and (1-beta/alpha) (CV=(1-ln2)/(1-beta/alpha)=0.307/(1-beta/alpha)) has been derived and was compared with the fraction (f(1)) of drug elimination or AUC (AUC-area under C vs t curve) associated with the first exponential term of the two-compartment equation (f(1)=A/alpha/AUC). Following i.v. bolus, CV ranges between a minimal value of 0.307 (1-ln2) and infinity. As long as f(1)t(1/2) and vice versa, and when f(1)=CV, then MRT=t(1/2). Following i.v. infusion and oral administration the denominator of the CV equation does not change but its numerator increases to (0.307+beta T/2) (T-infusion duration) and (0.307+beta/ka) (ka-absorption rate constant), respectively. Examples of various drugs are provided. For every drug that after i.v. bolus shows two-compartment disposition kinetics the following conclusions can be drawn (a) When f(1)<0.307, then f(1)t(1/2). (b) When beta/alpha>ln2, then CV>1>f(1) and thus(,) MRT>t(1/2). (c) When ln2>beta/alpha>(ln4-1), then 1>CV>0.5 and thus, in order for t(1/2)>MRT, f(1) has to be greater than its complementary fraction f(2) (f(1)>f(2)). (d) When beta/alpha<(ln4-1), it is possible that t(1/2)>MRT even when f(2)>f(1), as long as f(1)>CV. (e) As beta gets closer to alpha, CV approaches its maximal value (infinity) and therefore, the chances of MRT>t(1/2) are growing. (f) As beta becomes smaller compared with alpha, beta/alpha approaches zero, the denominator approaches unity and consequently, CV gets its minimal value and thus, the chances of t(1/2)>MRT are growing. (g) Following zero and first order input MRT increases compared with i.v. bolus and so does CV and thus, the chances of MRT>t(1/2) are growing. Copyright 2004 John Wiley & Sons, Ltd.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baserga, S.J.; Benz, E.J. Jr.

A number of premature translation termination mutations (nonsense mutations) have been described in the human {alpha}- and {beta}-globin genes. Studies on mRNA isolated from patients with {beta}{sup 0}-thalassemia have shown that for both the {beta}-17 and the {beta}-39 mutations less than normal levels of {beta}-globin mRNA accumulate in peripheral blood cells. (The codon at which the mutation occurs designates the name of the mutation; there are 146 codons in human {beta}-globin mRNA). In vitro studies using the cloned {beta}-39 gene have reproduced this effect in a heterologous transfection system and have suggested that the defect resides in intranuclear metabolism. Themore » authors have asked if this phenomenon of decreased mRNA accumulation is a general property of nonsense mutations and if the effect depends on the location or the type of mutation. Toward this end, they have studied the effect of five nonsense mutations and two missense mutations on the expression of human {beta}-globin mRNA in a heterologous transfection system. In all cases studied, the presence of a translation termination codon correlates with a decrease in the steady-state level of mRNA. The data suggest that the metabolism of a mammalian mRNA is affected by the presence of a mutation that affects translation.« less

X-ray and Sunyaev-Zel'dovich Effect Measurements of the Gas Mass Fraction in Galaxy Clusters

NASA Technical Reports Server (NTRS)

LaRoque, Samuel J.; Bonamente, Massimiliano; Carlstrom, John E.; Joy, Marshall K.; Nagai, Daisuke; Reese, Erik D.; Dawson, Kyle S.

2006-01-01

We present gas mass fractions of 38 massive galaxy clusters spanning redshifts from 0.14 to 0.89, derived from Chandra X-ray data and OVRO/BIMA interferometric Sunyaev-Zel' dovich Effect (SZE) measurements. We use three models for the gas distribution: (1) an isothermal Beta-model fit jointly to the X-ray data at radii beyond 100 kpc and to all of the SZE data, (2) a nonisothermal double Beta-model fit jointly to all of the X-ray and SZE data, and (3) an isothermal Beta-model fit only to the SZE spatial data. We show that the simple isothermal model well characterizes the intracluster medium (ICM) outside of the cluster core, and provides consistently good fits to clusters spanning a wide range of morphological properties. The agreement in the results shows that the core can be satisfactorily accounted for by either excluding the core in fits to the X-ray data (the 100 kpc-cut model) or modeling the intracluster gas with a non-isothermal double Beta-model. We find that the SZE is largely insensitive to structure in the core.

Relation between burnout syndrome and job satisfaction among mental health workers.

PubMed

Ogresta, Jelena; Rusac, Silvia; Zorec, Lea

2008-06-01

To identify predictors of burnout syndrome, such as job satisfaction and manifestations of occupational stress, in mental health workers. The study included a snowball sample of 174 mental health workers in Croatia. The following measurement instruments were used: Maslach Burnout Inventory, Manifestations of Occupational Stress Survey, and Job Satisfaction Survey. We correlated dimensions of burnout syndrome with job satisfaction and manifestations of occupational stress dimensions. We also performed multiple regression analysis using three dimensions of burnout syndrome--emotional exhaustion, depersonalization, and personal accomplishment. Stepwise multiple regression analysis showed that pay and rewards satisfaction (beta=-0.37), work climate (beta=-0.18), advancement opportunities (beta=0.17), the degree of psychological (beta=0.41), and physical manifestations of occupational stress (beta=0.29) were significant predictors of emotional exhaustion (R=0.76; F=30.02; P<0.001). The frequency of negative emotional and behavioral reactions toward patients and colleagues (beta=0.48), psychological (beta=0.27) and physical manifestations of occupational stress (beta=0.24), and pay and rewards satisfaction (beta=0.22) were significant predictors of depersonalization (R=0.57; F=13,01; P<0.001). Satisfaction with the work climate (beta=-0.20) was a significant predictor of lower levels of personal accomplishment (R=0.20; F=5.06; P<0.005). Mental health workers exhibited a moderate degree of burnout syndrome, but there were no significant differences regarding their occupation. Generally, both dimensions of job satisfaction and manifestations of occupational stress proved to be relevant predictors of burnout syndrome.

Dysregulation of glucocorticoid metabolism in murine obesity: comparable effects of leptin resistance and deficiency.

PubMed

Livingstone, Dawn E W; Grassick, Sarah L; Currie, Gillian L; Walker, Brian R; Andrew, Ruth

2009-05-01

In obese humans, metabolism of glucocorticoids by 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1) and A-ring reduction (by 5 alpha- and 5 beta-reductases) is dysregulated in a tissue specific manner. These changes have been recapitulated in leptin resistant obese Zucker rats but were not observed in high-fat fed Wistar rats. Recent data from mouse models suggest that such discrepancies may reflect differences in leptin signalling. We therefore compared glucocorticoid metabolism in murine models of leptin deficiency and resistance. Male ob/ob and db/db mice and their respective littermate controls (n=10-12/group) were studied at the age of 12 weeks. Enzyme activities and mRNA expression were quantified in snap-frozen tissues. The patterns of altered pathways of steroid metabolism in obesity were similar in ob/ob and db/db mice. In liver, 5 beta-reductase activity and mRNA were increased and 11 beta-HSD1 decreased in obese mice, whereas 5 alpha-reductase 1 (5 alpha R1) mRNA was not altered. In visceral adipose depots, 5 beta-reductase was not expressed, 11 beta-HSD1 activity was increased and 5 alpha R1 mRNA was not altered in obesity. By contrast, in subcutaneous adipose tissue 11 beta-HSD1 and 5 alpha R1 mRNA were decreased. Systematic differences were not found between ob/ob and db/db murine models of obesity, suggesting that variations in leptin signalling through the short splice variant of the Ob receptor do not contribute to dysregulation of glucocorticoid metabolism.

Golden Rice: introducing the beta-carotene biosynthesis pathway into rice endosperm by genetic engineering to defeat vitamin A deficiency.

PubMed

Beyer, Peter; Al-Babili, Salim; Ye, Xudong; Lucca, Paola; Schaub, Patrick; Welsch, Ralf; Potrykus, Ingo

2002-03-01

To obtain a functioning provitamin A (beta-carotene) biosynthetic pathway in rice endosperm, we introduced in a single, combined transformation effort the cDNA coding for phytoene synthase (psy) and lycopene beta-cyclase (beta-lcy) both from Narcissus pseudonarcissus and both under the control of the endosperm-specific glutelin promoter together with a bacterial phytoene desaturase (crtI, from Erwinia uredovora under constitutive 35S promoter control). This combination covers the requirements for beta-carotene synthesis and, as hoped, yellow beta-carotene-bearing rice endosperm was obtained in the T(0)-generation. Additional experiments revealed that the presence of beta-lcy was not necessary, because psy and crtI alone were able to drive beta-carotene synthesis as well as the formation of further downstream xanthophylls. Plausible explanations for this finding are that these downstream enzymes are constitutively expressed in rice endosperm or are induced by the transformation, e.g., by enzymatically formed products. Results using N. pseudonarcissus as a model system led to the development of a hypothesis, our present working model, that trans-lycopene or a trans-lycopene derivative acts as an inductor in a kind of feedback mechanism stimulating endogenous carotenogenic genes. Various institutional arrangements for disseminating Golden Rice to research institutes in developing countries also are discussed.

Ubiquitin ligase Nedd4L targets activated Smad2/3 to limit TGF-beta signaling.

PubMed

Gao, Sheng; Alarcón, Claudio; Sapkota, Gopal; Rahman, Sadia; Chen, Pan-Yu; Goerner, Nina; Macias, Maria J; Erdjument-Bromage, Hediye; Tempst, Paul; Massagué, Joan

2009-11-13

TGF-beta induces phosphorylation of the transcription factors Smad2 and Smad3 at the C terminus as well as at an interdomain linker region. TGF-beta-induced linker phosphorylation marks the activated Smad proteins for proteasome-mediated destruction. Here, we identify Nedd4L as the ubiquitin ligase responsible for this step. Through its WW domain, Nedd4L specifically recognizes a TGF-beta-induced phosphoThr-ProTyr motif in the linker region, resulting in Smad2/3 polyubiquitination and degradation. Nedd4L is not interchangeable with Smurf1, a ubiquitin ligase that targets BMP-activated, linker-phosphorylated Smad1. Nedd4L limits the half-life of TGF-beta-activated Smads and restricts the amplitude and duration of TGF-beta gene responses, and in mouse embryonic stem cells, it limits the induction of mesoendodermal fates by Smad2/3-activating factors. Hierarchical regulation is provided by SGK1, which phosphorylates Nedd4L to prevent binding of Smad2/3. Previously identified as a regulator of renal sodium channels, Nedd4L is shown here to play a broader role as a general modulator of Smad turnover during TGF-beta signal transduction.

The quest to make fully functional human pancreatic beta cells from embryonic stem cells: climbing a mountain in the clouds.

PubMed

Johnson, James D

2016-10-01

The production of fully functional insulin-secreting cells to treat diabetes is a major goal of regenerative medicine. In this article, I review progress towards this goal over the last 15 years from the perspective of a beta cell biologist. I describe the current state-of-the-art, and speculate on the general approaches that will be required to identify and achieve our ultimate goal of producing functional beta cells. The need for deeper phenotyping of heterogeneous cultures of stem cell derived islet-like cells in parallel with a better understanding of the heterogeneity of the target cell type(s) is emphasised. This deep phenotyping should include high-throughput single-cell analysis, as well as comprehensive 'omics technologies to provide unbiased characterisation of cell products and human beta cells. There are justified calls for more detailed and well-powered studies of primary human pancreatic beta cell physiology, and I propose online databases of standardised human beta cell responses to physiological stimuli, including both functional and metabolomic/proteomic/transcriptomic profiles. With a concerted, community-wide effort, including both basic and applied scientists, beta cell replacement will become a clinical reality for patients with diabetes.

Synergy between TGF-beta 3 and NT-3 to promote the survival of spiral ganglia neurones in vitro.

PubMed

Marzella, P L; Clark, G M; Shepherd, R K; Bartlett, P F; Kilpatrick, T J

1998-01-09

Transforming growth factor-betas (TGF-betas) have been implicated in normal inner ear development and in promoting neuronal survival. Early rat post-natal spiral ganglion cells (SGC) in dissociated cell culture were used as a model of auditory innervation to test the trophic factors TGF-beta3 and neurotrophin-3 (NT-3) for their ability, individually or in combination, to promote neuronal survival. The findings from this study suggest that TGF-beta3 supports neuronal survival in a concentration-dependent manner. Moreover TGF-beta3 and NT-3-potentiated spiral ganglion neuronal survival in a synergistic fashion.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wemhoff, A P; Burnham, A K; Nichols III, A L

The reduction of the number of reactions in kinetic models for both the HMX beta-delta phase transition and thermal cookoff provides an attractive alternative to traditional multi-stage kinetic models due to reduced calibration effort requirements. In this study, we use the LLNL code ALE3D to provide calibrated kinetic parameters for a two-reaction bidirectional beta-delta HMX phase transition model based on Sandia Instrumented Thermal Ignition (SITI) and Scaled Thermal Explosion (STEX) temperature history curves, and a Prout-Tompkins cookoff model based on One-Dimensional Time to Explosion (ODTX) data. Results show that the two-reaction bidirectional beta-delta transition model presented here agrees as wellmore » with STEX and SITI temperature history curves as a reversible four-reaction Arrhenius model, yet requires an order of magnitude less computational effort. In addition, a single-reaction Prout-Tompkins model calibrated to ODTX data provides better agreement with ODTX data than a traditional multi-step Arrhenius model, and can contain up to 90% less chemistry-limited time steps for low-temperature ODTX simulations. Manual calibration methods for the Prout-Tompkins kinetics provide much better agreement with ODTX experimental data than parameters derived from Differential Scanning Calorimetry (DSC) measurements at atmospheric pressure. The predicted surface temperature at explosion for STEX cookoff simulations is a weak function of the cookoff model used, and a reduction of up to 15% of chemistry-limited time steps can be achieved by neglecting the beta-delta transition for this type of simulation. Finally, the inclusion of the beta-delta transition model in the overall kinetics model can affect the predicted time to explosion by 1% for the traditional multi-step Arrhenius approach, while up to 11% using a Prout-Tompkins cookoff model.« less

Sgr A* Emission Parametrizations from GRMHD Simulations

NASA Astrophysics Data System (ADS)

Anantua, Richard; Ressler, Sean; Quataert, Eliot

2018-06-01

Galactic Center emission near the vicinity of the central black hole, Sagittarius (Sgr) A*, is modeled using parametrizations involving the electron temperature, which is found from general relativistic magnetohydrodynamic (GRMHD) simulations to be highest in the disk-outflow corona. Jet-motivated prescriptions generalizing equipartition of particle and magnetic energies, e.g., by scaling relativistic electron energy density to powers of the magnetic field strength, are also introduced. GRMHD jet (or outflow)/accretion disk/black hole (JAB) simulation postprocessing codes IBOTHROS and GRMONTY are employed in the calculation of images and spectra. Various parametric models reproduce spectral and morphological features, such as the sub-mm spectral bump in electron temperature models and asymmetric photon rings in equipartition-based models. The Event Horizon Telescope (EHT) will provide unprecedentedly high-resolution 230+ GHz observations of the "shadow" around Sgr A*'s supermassive black hole, which the synthetic models presented here will reverse-engineer. Both electron temperature and equipartition-based models can be constructed to be compatible with EHT size constraints for the emitting region of Sgr A*. This program sets the groundwork for devising a unified emission parametrization flexible enough to model disk, corona and outflow/jet regions with a small set of parameters including electron heating fraction and plasma beta.

Gauge coupling beta functions in the standard model to three loops.

PubMed

Mihaila, Luminita N; Salomon, Jens; Steinhauser, Matthias

2012-04-13

In this Letter, we compute the three-loop corrections to the beta functions of the three gauge couplings in the standard model of particle physics using the minimal subtraction scheme and taking into account Yukawa and Higgs self-couplings.

Accounting for non-independent detection when estimating abundance of organisms with a Bayesian approach

USGS Publications Warehouse

Martin, Julien; Royle, J. Andrew; MacKenzie, Darryl I.; Edwards, Holly H.; Kery, Marc; Gardner, Beth

2011-01-01

Summary 1. Binomial mixture models use repeated count data to estimate abundance. They are becoming increasingly popular because they provide a simple and cost-effective way to account for imperfect detection. However, these models assume that individuals are detected independently of each other. This assumption may often be violated in the field. For instance, manatees (Trichechus manatus latirostris) may surface in turbid water (i.e. become available for detection during aerial surveys) in a correlated manner (i.e. in groups). However, correlated behaviour, affecting the non-independence of individual detections, may also be relevant in other systems (e.g. correlated patterns of singing in birds and amphibians). 2. We extend binomial mixture models to account for correlated behaviour and therefore to account for non-independent detection of individuals. We simulated correlated behaviour using beta-binomial random variables. Our approach can be used to simultaneously estimate abundance, detection probability and a correlation parameter. 3. Fitting binomial mixture models to data that followed a beta-binomial distribution resulted in an overestimation of abundance even for moderate levels of correlation. In contrast, the beta-binomial mixture model performed considerably better in our simulation scenarios. We also present a goodness-of-fit procedure to evaluate the fit of beta-binomial mixture models. 4. We illustrate our approach by fitting both binomial and beta-binomial mixture models to aerial survey data of manatees in Florida. We found that the binomial mixture model did not fit the data, whereas there was no evidence of lack of fit for the beta-binomial mixture model. This example helps illustrate the importance of using simulations and assessing goodness-of-fit when analysing ecological data with N-mixture models. Indeed, both the simulations and the goodness-of-fit procedure highlighted the limitations of the standard binomial mixture model for aerial manatee surveys. 5. Overestimation of abundance by binomial mixture models owing to non-independent detections is problematic for ecological studies, but also for conservation. For example, in the case of endangered species, it could lead to inappropriate management decisions, such as downlisting. These issues will be increasingly relevant as more ecologists apply flexible N-mixture models to ecological data.

Consistent patterns of high alpha and low beta diversity in tropical parasitic and free-living protists.

PubMed

Lentendu, Guillaume; Mahé, Frédéric; Bass, David; Rueckert, Sonja; Stoeck, Thorsten; Dunthorn, Micah

2018-05-30

Tropical animals and plants are known to have high alpha diversity within forests, but low beta diversity between forests. By contrast, it is unknown whether microbes inhabiting the same ecosystems exhibit similar biogeographic patterns. To evaluate the biogeographies of tropical protists, we used metabarcoding data of species sampled in the soils of three lowland Neotropical rainforests. Taxa-area and distance-decay relationships for three of the dominant protist taxa and their subtaxa were estimated at both the OTU and phylogenetic levels, with presence-absence and abundance-based measures. These estimates were compared to null models. High local alpha and low regional beta diversity patterns were consistently found for both the parasitic Apicomplexa and the largely free-living Cercozoa and Ciliophora. Similar to animals and plants, the protists showed spatial structures between forests at the OTU and phylogenetic levels, and only at the phylogenetic level within forests. These results suggest that the biogeographies of macro- and micro-organismal eukaryotes in lowland Neotropical rainforests are partially structured by the same general processes. However, and unlike the animals and plants, the protist OTUs did not exhibit spatial structures within forests, which hinders our ability to estimate the local and regional diversity of protists in tropical forests. © 2018 John Wiley & Sons Ltd.

Sevoflurane Induces Coherent Slow-Delta Oscillations in Rats.

PubMed

Guidera, Jennifer A; Taylor, Norman E; Lee, Justin T; Vlasov, Ksenia Y; Pei, JunZhu; Stephen, Emily P; Mayo, J Patrick; Brown, Emery N; Solt, Ken

2017-01-01

Although general anesthetics are routinely administered to surgical patients to induce loss of consciousness, the mechanisms underlying anesthetic-induced unconsciousness are not fully understood. In rats, we characterized changes in the extradural EEG and intracranial local field potentials (LFPs) within the prefrontal cortex (PFC), parietal cortex (PC), and central thalamus (CT) in response to progressively higher doses of the inhaled anesthetic sevoflurane. During induction with a low dose of sevoflurane, beta/low gamma (12-40 Hz) power increased in the frontal EEG and PFC, PC and CT LFPs, and PFC-CT and PFC-PFC LFP beta/low gamma coherence increased. Loss of movement (LOM) coincided with an abrupt decrease in beta/low gamma PFC-CT LFP coherence. Following LOM, cortically coherent slow-delta (0.1-4 Hz) oscillations were observed in the frontal EEG and PFC, PC and CT LFPs. At higher doses of sevoflurane sufficient to induce loss of the righting reflex, coherent slow-delta oscillations were dominant in the frontal EEG and PFC, PC and CT LFPs. Dynamics similar to those observed during induction were observed as animals emerged from sevoflurane anesthesia. We conclude that the rat is a useful animal model for sevoflurane-induced EEG oscillations in humans, and that coherent slow-delta oscillations are a correlate of sevoflurane-induced behavioral arrest and loss of righting in rats.

Electronic Health Record Patient Portal Adoption by Health Care Consumers: An Acceptance Model and Survey.

PubMed

Tavares, Jorge; Oliveira, Tiago

2016-03-02

The future of health care delivery is becoming more citizen centered, as today's user is more active, better informed, and more demanding. Worldwide governments are promoting online health services, such as electronic health record (EHR) patient portals and, as a result, the deployment and use of these services. Overall, this makes the adoption of patient-accessible EHR portals an important field to study and understand. The aim of this study is to understand the factors that drive individuals to adopt EHR portals. We applied a new adoption model using, as a starting point, Ventkatesh's Unified Theory of Acceptance and Use of Technology in a consumer context (UTAUT2) by integrating a new construct specific to health care, a new moderator, and new relationships. To test the research model, we used the partial least squares (PLS) causal modelling approach. An online questionnaire was administrated. We collected 360 valid responses. The statistically significant drivers of behavioral intention are performance expectancy (beta=.200; t=3.619), effort expectancy (beta=.185; t=2.907), habit (beta=.388; t=7.320), and self-perception (beta=.098; t=2.285). The predictors of use behavior are habit (beta=0.206; t=2.752) and behavioral intention (beta=0.258; t=4.036). The model explained 49.7% of the variance in behavioral intention and 26.8% of the variance in use behavior. Our research helps to understand the desired technology characteristics of EHR portals. By testing an information technology acceptance model, we are able to determine what is more valued by patients when it comes to deciding whether to adopt EHR portals or not. The inclusion of specific constructs and relationships related to the health care consumer area also had a significant impact on understanding the adoption of EHR portals.

Double beta decays of {sup 106}Cd

DOE Office of Scientific and Technical Information (OSTI.GOV)

Suhonen, Jouni

2011-12-16

The two-neutrino (2{nu}2{beta}) and neutrinoless (0{nu}2{beta}) double beta decays of {sup 106}Cd are studied for the transitions to the ground state 0{sub gs}{sup +} and 0{sup +} and 2{sup +} excited states in {sup 106}Pd by using realistic many-body wave functions calculated in the framework of the quasiparticle random-phase approximation. Effective, G-matrix-derived nuclear forces are used in realistic single-particle model spaces. All the possible channels, {beta}{sup +}{beta}{sup +}, {beta}{sup +}EC, and ECEC, are discussed for both the 2{nu}2{beta} and 0{nu}2{beta} decays. The associated half-lives are computed and particular attention is devoted to the study of the detectability of the resonantmore » neutrinoless double electron capture (R0{nu}ECEC) process in {sup 106}Cd. The calculations of the present article constitute the thus far most complete and up-to-date investigation of the double-beta-decay properties of {sup 106}Cd.« less

Gene-gene interactions among genetic variants from obesity candidate genes for nonobese and obese populations in type 2 diabetes.

PubMed

Lin, Eugene; Pei, Dee; Huang, Yi-Jen; Hsieh, Chang-Hsun; Wu, Lawrence Shih-Hsin

2009-08-01

Recent studies indicate that obesity may play a key role in modulating genetic predispositions to type 2 diabetes (T2D). This study examines the main effects of both single-locus and multilocus interactions among genetic variants in Taiwanese obese and nonobese individuals to test the hypothesis that obesity-related genes may contribute to the etiology of T2D independently and/or through such complex interactions. We genotyped 11 single nucleotide polymorphisms for 10 obesity candidate genes including adrenergic beta-2-receptor surface, adrenergic beta-3-receptor surface, angiotensinogen, fat mass and obesity associated gene, guanine nucleotide binding protein beta polypeptide 3 (GNB3), interleukin 6 receptor, proprotein convertase subtilisin/kexin type 1 (PCSK1), uncoupling protein 1, uncoupling protein 2, and uncoupling protein 3. There were 389 patients diagnosed with T2D and 186 age- and sex-matched controls. Single-locus analyses showed significant main effects of the GNB3 and PCSK1 genes on the risk of T2D among the nonobese group (p = 0.002 and 0.047, respectively). Further, interactions involving GNB3 and PCSK1 were suggested among the nonobese population using the generalized multifactor dimensionality reduction method (p = 0.001). In addition, interactions among angiotensinogen, fat mass and obesity associated gene, GNB3, and uncoupling protein 3 genes were found in a significant four-locus generalized multifactor dimensionality reduction model among the obese population (p = 0.001). The results suggest that the single nucleotide polymorphisms from the obesity candidate genes may contribute to the risk of T2D independently and/or in an interactive manner according to the presence or absence of obesity.

Design, synthesis and bioactivity evaluation of tribactam beta lactamase inhibitors.

PubMed

Copar, Anton; Prevec, Tadeja; Anzic, Borut; Mesar, Tomaz; Selic, Lovro; Vilar, Mateja; Solmajer, Tom

2002-03-25

Known carbapenem compounds with inhibitory effect towards beta-lactamase enzymes are formed from bicyclical beta lactam structural scaffolds. On the basis of results from theoretical computational methods and molecular modelling we have designed and developed a synthetic route towards novel, biologically active tricyclic derivatives of carbapenems.

49 CFR 572.121 - General description.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Dummy, Beta Version § 572.121 General description. (a) The Hybrid III type 6-year-old dummy is defined... specifications package P/N 127-0000, the titles of which are listed in Table A; (2) Procedures for Assembly...

No significant association between the genetic polymorphisms in the GSK-3 beta gene and schizophrenia in the Chinese population.

PubMed

Meng, Junwei; Shi, Yongyong; Zhao, Xinzhi; Zhou, Jian; Zheng, Yonglan; Tang, Ruqi; Ma, Gang; Zhu, Xuming; He, Zangdong; Wang, Zhe; Xu, Yifeng; Feng, Guoyin; He, Lin

2008-04-01

The GSK-3 beta gene encodes a protein kinase which is abundant in the brain, and its product is involved in signal transduction cascades of neuronal cell development, energy metabolism and body pattern formation. Previous studies have suggested that GSK-3 beta might act as a potential candidate locus for schizophrenia susceptibility. We genotyped six SNPs within the gene and conducted a case-control study involving 329 schizophrenic patients and 288 healthy subjects in the Chinese population. We examined allele and genotype frequencies and haplotype distributions in the subtype of paranoid schizophrenic patients as well as schizophrenic subjects in general. Our results fail to replicate the association of the GSK-3 beta gene with susceptibility to schizophrenia in the Chinese population.

The influence of the preparation methods on the inclusion of model drugs in a beta-cyclodextrin cavity.

PubMed

Salústio, P J; Feio, G; Figueirinhas, J L; Pinto, J F; Cabral Marques, H M

2009-02-01

The work aims to prove the complexation of two model drugs (ibuprofen, IB and indomethacin, IN) by beta-cyclodextrin (betaCD), and the effect of water in such a process, and makes a comparison of their complexation yields. Two methods were considered: kneading of a binary mixture of the drug, betaCD, and inclusion of either IB or IN in aqueous solutions of betaCD. In the latter method water was removed by air stream, spray-drying and freeze-drying. To prove the formation of complexes in final products, optical microscopy, UV spectroscopy, IR spectroscopy, DSC, X-ray and NMR were considered. Each powder was added to an acidic solution (pH=2) to quantify the concentration of the drug inside betaCD cavity. Other media (pH=5 and 7) were used to prove the existence of drug not complexed in each powder, as the drugs solubility increases with the pH. It was observed that complexation occurred in all powders, and that the fraction of drug inside the betaCD did not depend neither on the method of complexation nor on the processes of drying considered.

Analytical functions for beta and gamma absorbed fractions of iodine-131 in spherical and ellipsoidal volumes.

PubMed

Mowlavi, Ali Asghar; Fornasier, Maria Rossa; Mirzaei, Mohammd; Bregant, Paola; de Denaro, Mario

2014-10-01

The beta and gamma absorbed fractions in organs and tissues are the important key factors of radionuclide internal dosimetry based on Medical Internal Radiation Dose (MIRD) approach. The aim of this study is to find suitable analytical functions for beta and gamma absorbed fractions in spherical and ellipsoidal volumes with a uniform distribution of iodine-131 radionuclide. MCNPX code has been used to calculate the energy absorption from beta and gamma rays of iodine-131 uniformly distributed inside different ellipsoids and spheres, and then the absorbed fractions have been evaluated. We have found the fit parameters of a suitable analytical function for the beta absorbed fraction, depending on a generalized radius for ellipsoid based on the radius of sphere, and a linear fit function for the gamma absorbed fraction. The analytical functions that we obtained from fitting process in Monte Carlo data can be used for obtaining the absorbed fractions of iodine-131 beta and gamma rays for any volume of the thyroid lobe. Moreover, our results for the spheres are in good agreement with the results of MIRD and other scientific literatures.

Non-group A streptococci in the pharynx. Pathogens or innocent bystanders?

PubMed

Hayden, G F; Murphy, T F; Hendley, J O

1989-07-01

To determine whether beta-hemolytic streptococci from groups other than A are an important cause of sporadic pharyngitis in children. Cross-sectional, case-referent survey. General pediatric clinic at a military base in Ohio. One hundred fifty children with symptomatic pharyngitis and 150 controls matched for age and time of presentation over a 20-month study period. None. Anaerobic culture technique was used to improve isolation of beta-hemolytic streptococci. Group A beta-hemolytic streptococci were detected significantly more often among the ill children than among the controls (39% vs 16%, respectively). In contrast, non-group A beta-hemolytic streptococci were isolated in similar frequency from the ill and control children (17% vs 21%, respectively). Non-group A beta-hemolytic streptococci from groups B, C, F, and G were each isolated in similar frequency among the ill and control children. The isolation rate of non-group A organisms increased with age among both patients and controls. Non-group A beta-hemolytic streptococci seemed not to be an important cause of sporadic pharyngitis in this pediatric population.

Measuring motivation and volition of nursing students in nontraditional learning environments.

PubMed

Nagelsmith, Laurie; Bryer, Jason; Yan, Zheng

2012-01-01

The purpose of this study was to identify the best fitting model to represent interrelationships between motivation, volition, and academic success for adult nursing students learning in nontraditional environments. Participants (N=297) completed a survey that incorporated two measures: the Motivated Strategies for Learning Questionnaire (MSLQ) and the academic volitional strategies inventory (AVSI) as well as demographic information. Exploratory factor analysis (EFA), confirmatory factor analysis (CFA), and structural equation modeling (SEM) were used for data analysis. In phase 1, EFA resulted in factors that generally aligned with previous theoretical factors as defined by the psychometrics used. In Phase 2 of the analysis, CFA validated the use of predefined factor structures. In Phase 3, SEM analysis revealed that motivation has a larger effect on grade point average (GPA; beta = .28, p < .01) than volition (beta = .15, p < .05). The covariance between motivation and volition (r = .42, p < .01) was also found to be significant. These results suggest that there is a significant relationship among motivation, volition, and academic success for adult learners studying in nontraditional learning environments. These findings are consistent with and elaborate the relationship between motivation and volition with a population and setting underrepresented in the research.

A transgenic model of transactivation by the Tax protein of HTLV-I.

PubMed

Bieberich, C J; King, C M; Tinkle, B T; Jay, G

1993-09-01

The human T-lymphotropic virus type I (HTLV-I) Tax protein is a transcriptional regulatory protein that has been suggested to play a causal role in the development of several HTLV-I-associated diseases. Tax regulates expression of its own LTR and of certain cellular promoters perhaps by usurping the function of the host transcriptional machinery. We have established a transgenic mouse model system to define the spectrum of tissues in vivo that are capable of supporting Tax-mediated transcriptional transactivation. Transgenic mice carrying the HTLV-I LTR driving expression of the Escherichia coli beta-galactosidase (beta gal) gene were generated, and this LTR-beta gal gene was transcriptionally inactive in all tissues. When LTR-beta gal mice were mated to transgenic mice carrying the same LTR driving expression of the HTLV-I tax gene, mice that carried both transgenes showed restricted expression of the beta gal reporter gene in several tissues including muscle, bone, salivary glands, skin, and nerve. In addition, a dramatic increase in the number of beta gal-expressing cells was seen in response to wounding. These observations provide direct evidence for viral transactivation in vivo, delimit the tissues capable of supporting that transactivation, and provide a model system to study the mechanism of gene regulation by Tax.

Transforming growth factor-beta production in anti-glomerular basement membrane disease in the rabbit.

PubMed Central

Coimbra, T.; Wiggins, R.; Noh, J. W.; Merritt, S.; Phan, S. H.

1991-01-01

The purpose of this study was to assay for the presence of collagen synthesis stimulatory activity in the kidney during immune-induced renal injury that results in severe fibrosis in both glomerular and interstitial compartments. A model of antiglomerular basement (anti-GBM) disease in the rabbit was induced on day 0 by the injection of anti-GBM antibody and renal cortex tissues were then sampled at various time points. Only conditioned media prepared from diseased renal cortical samples showed collagen synthesis stimulatory activity when tested on rabbit mesangial cells. The activity had an estimated molecular weight range of 16 to 25 kd and was neutralized by antibody to transforming growth factor-beta (TGF-beta). A standard assay for TGF-beta using a mink lung epithelial cell line confirmed the increase in TGF-beta activity in conditioned media of diseased cortex from day 7 and day 14 animals, which was not significantly activated by previous acidification. This suggests that most of the TGF-beta present in renal conditioned media was in the active form. The increase in renal cortical secretion of active TGF-beta was accompanied by increases in renal cortical TGF-beta mRNA content on days 4 and 7 after induction, with subsequent return to control levels. A similar increase in TGF-beta activity was present in nonacidified conditioned media of purified glomeruli from diseased days 7 and 14 animals, which was also accompanied by significant increases in TGF-beta mRNA. However with acidification no significant differences were noted between control and diseased samples, suggesting the presence of substantial latent TGF-beta activity in control glomerular conditioned media. These same control-conditioned media contained inhibitor activity for added exogenous TGF-beta. These results support the conclusion that the association between increased TGF-beta secretion and increased renal cortical collagen synthesis in this model is consistent with a role for this cytokine in directing fibrogenesis in the kidney. Images Figure 6 PMID:1987768

75 FR 41104 - Airworthiness Directives; Robinson Helicopter Company (Robinson) Model R22, R22 Alpha, R22 Beta...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-15

...-0711; Directorate Identifier 2008-SW-25-AD] RIN 2120-AA64 Airworthiness Directives; Robinson Helicopter Company (Robinson) Model R22, R22 Alpha, R22 Beta, and R22 Mariner Helicopters, and Model R44, and R44 II...). SUMMARY: This document proposes adopting a new airworthiness directive (AD) for Robinson Model R22, R22...

Evaluation of thrombogenicity of beta-propiolactone/ultraviolet (beta-PL/UV) treated PPSB in chimpanzees

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kotitschke, R.; Stephan, W.; Prince, A.M.

1983-05-01

The thrombogenicity of beta-PL/UV-treated PPSB (factor IX concentrate) was evaluated in chimpanzees. PPSB isolated from beta-propiolactone-treated and UV-irradiated plasma was injected into chimpanzees at a dose of approximately 100 units/kg body weight. An FDA licensed PPSB preparation served as the negative control, and a preparation containing activated as well as precursor clotting factors served as the positive control. 15 minutes, 1 h, 4 h, and 24 h after the PPSB application the following parameters were determined in the chimpanzee blood: factors II, VII, IX, X, VIII, fibrinogen, AT III, thrombin coagulase, Quick value, APTT and platelet count. Neither the untreatedmore » control preparation, nor the PPSB isolated from beta-propiolactone-treated and UV-irradiated plasma, showed signs of thrombogenicity in the chimpanzee model. The positive control indicated that the chimpanzee is a suitable model for the thrombogenicity testing of activated clotting factors.« less

High-beta extended MHD simulations of stellarators

NASA Astrophysics Data System (ADS)

Bechtel, T. A.; Hegna, C. C.; Sovinec, C. R.; Roberds, N. A.

2016-10-01

The high beta properties of stellarator plasmas are studied using the nonlinear, extended MHD code NIMROD. In this work, we describe recent developments to the semi-implicit operator which allow the code to model 3D plasma evolution with better accuracy and efficiency. The configurations under investigation are an l=2, M=5 torsatron with geometry modeled after the Compact Toroidal Hybrid (CTH) experiment and an l=2, M=10 torsatron capable of having vacuum rotational transform profiles near unity. High-beta plasmas are created using a volumetric heating source and temperature dependent anisotropic thermal conduction and resistivity. To reduce computation expenses, simulations are initialized from stellarator symmetric pseudo-equilibria by turning on symmetry breaking modes at finite beta. The onset of MHD instabilities and nonlinear consequences are monitored as a function of beta as well as the fragility of the magnetic surfaces. Research supported by US DOE under Grant No. DE-FG02-99ER54546.

Nanoscale organization of {beta}{sub 2}-adrenergic receptor-Venus fusion protein domains on the surface of mammalian cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vobornik, Dusan; Rouleau, Yanouchka; Haley, Jennifer

2009-04-24

Adrenergic receptors are a key component of nanoscale multiprotein complexes that are responsible for controlling the beat rate in a mammalian heart. We demonstrate the ability of near-field scanning optical microscopy (NSOM) to visualize {beta}{sub 2}-adrenergic receptors ({beta}{sub 2}AR) fused to the GFP analogue Venus at the nanoscale on HEK293 cells. The expression of the {beta}{sub 2}AR-Venus fusion protein was tightly controlled using a tetracycline-induced promoter. Both the size and density of the observed nanoscale domains are dependent on the level of induction and thus the level of protein expression. At concentrations between 100 and 700 ng/ml of inducer doxycycline,more » the size of domains containing the {beta}{sub 2}AR-Venus fusion protein appears to remain roughly constant, but the number of domains per cell increase. At 700 ng/ml doxycycline the functional receptors are organized into domains with an average diameter of 150 nm with a density similar to that observed for the native protein on primary murine cells. By contrast, larger micron-sized domains of {beta}{sub 2}AR are observed in the membrane of the HEK293 cells that stably overexpress {beta}{sub 2}AR-GFP and {beta}{sub 2}AR-eYFP. We conclude that precise chemical control of gene expression is highly advantageous for the use {beta}{sub 2}AR-Venus fusion proteins as models for {beta}{sub 2}AR function. These observations are critical for designing future cell models and assays based on {beta}{sub 2}AR, since the receptor biology is consistent with a relatively low density of nanoscale receptor domains.« less

Genetic models rule out a major role of beta cell glycogen in the control of glucose homeostasis.

PubMed

Mir-Coll, Joan; Duran, Jordi; Slebe, Felipe; García-Rocha, Mar; Gomis, Ramon; Gasa, Rosa; Guinovart, Joan J

2016-05-01

Glycogen accumulation occurs in beta cells of diabetic patients and has been proposed to partly mediate glucotoxicity-induced beta cell dysfunction. However, the role of glycogen metabolism in beta cell function and its contribution to diabetes pathophysiology remain poorly understood. We investigated the function of beta cell glycogen by studying glucose homeostasis in mice with (1) defective glycogen synthesis in the pancreas; and (2) excessive glycogen accumulation in beta cells. Conditional deletion of the Gys1 gene and overexpression of protein targeting to glycogen (PTG) was accomplished by Cre-lox recombination using pancreas-specific Cre lines. Glucose homeostasis was assessed by determining fasting glycaemia, insulinaemia and glucose tolerance. Beta cell mass was determined by morphometry. Glycogen was detected histologically by periodic acid-Schiff's reagent staining. Isolated islets were used for the determination of glycogen and insulin content, insulin secretion, immunoblots and gene expression assays. Gys1 knockout (Gys1 (KO)) mice did not exhibit differences in glucose tolerance or basal glycaemia and insulinaemia relative to controls. Insulin secretion and gene expression in isolated islets was also indistinguishable between Gys1 (KO) and controls. Conversely, despite effective glycogen overaccumulation in islets, mice with PTG overexpression (PTG(OE)) presented similar glucose tolerance to controls. However, under fasting conditions they exhibited lower glycaemia and higher insulinaemia. Importantly, neither young nor aged PTG(OE) mice showed differences in beta cell mass relative to age-matched controls. Finally, a high-fat diet did not reveal a beta cell-autonomous phenotype in either model. Glycogen metabolism is not required for the maintenance of beta cell function. Glycogen accumulation in beta cells alone is not sufficient to trigger the dysfunction or loss of these cells, or progression to diabetes.

Biosynthesis of ketomycin. (II) biomimetic model for beta-lactamase catalysis: host-guest interactions in cyclodextrin-penicillin inclusion complex

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mak, H.W.

The antibiotic ketomycin is formed from shikimic acid via chorismic acid and prephenic acid. Phenylalanine and 2',5'-dihydrophenylalanine derived from shikimic acid are not intermediates in the biosynthesis. Degradation of ketomycin derived from (1,6-/sup 14/C)shikimic acid showed that prephenic acid is converted into ketomycin with stereospecific discrimination between the two enantiotopic edges of the ring, the pro-S-R edge giving rise to the C-2', C-3' side of the cyclohexane ring of ketomycin. The resistance of pathogenic bacteria to the action of ..beta..-lactam antibiotics is mainly ascribed to their ability to produce ..beta..-lactamase to cleave the ..beta..-lactam ring. It is essential to understandmore » the molecular nature of ..beta..-lactamase-penicillin recognition for designing and formulating more effective ..beta..-lactam antibiotics. A biomimetic study of ..beta..-lactamase is therefore initiated. To meet the requirements of hydrophobic and serine protease characteristics of ..beta..-lactamase, ..cap alpha..-cyclodextrin is chosen as a biomimetic model for ..beta..-lactamase. The structural specificity and the chemical dynamics of ..cap alpha..-cyclodextrin-phenoxymethyl penicillin inclusion complex in solid state and in solution have been determined by IR and NMR spectroscopy. The spectral results strongly indicate that the phenyl portion of the phenoxymethyl penicillin forms a stable inclusion complex with the hydrophobic cavity of ..cap alpha..-cyclodextrin in solution as well as in the solid state. Kinetic studies followed by /sup 1/HNMR and HPLC analyses under alkaline condition have shown that the ..cap alpha..-cyclodextrin mimics the catalytic function of serine of ..beta..-lactamase in the stereospecific hydrolysis of the ..beta..-lactam ring of phenoxymethyl penicillin.« less

Inhibitory effect of dimeric beta peptide on the recurrence and metastasis of hepatocellular carcinoma in vitro and in mice.

PubMed

Wang, Song-Mei; Zhu, Jun; Pan, Luan-Feng; Liu, Yin-Kun

2008-05-21

To block the adhesion of tumor cells to the extracellular matrix, and prevent tumor metastasis and recurrence, the dimer of the beta peptide (DLYYLMDLSYSMKGGDLYYLMDLSYSMK, beta2) was designed and synthesized and its anti-adhesion and anti-invasion effects on hepatocellular carcinoma cells were assessed. Additionally, its influence on the metastasis and recurrence of mouse hepatocellular carcinoma was measured. The anti-adhesion effect of beta2 on the highly metastatic hepatocellular carcinoma cell line HCCLM6 cells and fibronectin (FN) was assayed by the MTT assay. The inhibition of invasion of HCCLM6 cells by beta2 was observed using a Transwell (modified Boyden chamber) and matrigel. Using the hepatocellular carcinoma metastasis model and LCI-D20 nude mice, the influence of beta2 on the metastasis and recurrence of hepatocellular carcinoma after early resection was investigated. HCCLM6 cells co-incubated with 100 mumol/L, 50 micromol/L, 20 micromol/L or 10 micromol/L beta2 for 3 h showed an obvious decrease in adhesion to FN. The adhesion inhibition ratios were 11.8%, 21.7%, 29.6% and 48.7%, respectively. Additionally, HCCLM6 cells cultured with 100 mumol/L beta2 had a dramatic decrease in cell invasion. beta2 was also observed to inhibit the incisal edge recurrence and the distant metastasis of nude mice hepatocellular carcinoma after early resection (P < 0.05). The beta2 peptide can specifically block the adhesion and invasion of HCCLM6 cells, and can inhibit HCC recurrence and metastasis of LCI-D20 model posthepatectomy in vivo. Thus, beta2 should be further studied as a new anti-tumor drug.

Perceived parenting style and practices and the consumption of sugar-sweetened beverages by adolescents.

PubMed

van der Horst, Klazine; Kremers, Stef; Ferreira, Isabel; Singh, Amika; Oenema, Anke; Brug, Johannes

2007-04-01

The purpose of this study was to investigate whether perceived parenting practices and parenting style dimensions (strictness and involvement) are associated with adolescents' consumption of sugar-sweetened beverages. In this cross-sectional study, secondary school students (n = 383, mean age 13.5 years) completed a self-administered questionnaire on their consumption of sugar-sweetened beverages, attitude, social influences, self-efficacy, habit strength, food-related parenting practices and the general parenting style dimensions of 'strictness' and 'involvement'. Data were analyzed using multiple linear regression analyses. More restrictive parenting practices were associated with lower consumption of sugar-sweetened beverages (beta = -38.0 ml; 95% CI = -48.1, -28.0). This association was highly mediated ( approximately 55%) by attitude, self-efficacy and modeling from parents. Nevertheless, a significant direct effect remained (beta = -17.1 ml; 95% CI = -27.2, -6.90). Interactions between perceived parenting style and parenting practices showed that the association between parenting practices and sugar-sweetened beverage consumption was stronger among adolescents who perceived their parents as being moderately strict and highly involved. Parents influence their children's sugar-sweetened beverage consumption and should therefore be involved in interventions aimed at changing dietary behaviors. Interventions aimed at the promotion of healthy parenting practices will improve when they are tailored to the general parenting style of the participants.

Origin of a sensitive dependence of calculated {beta}{beta}-decay amplitudes on the particle-particle residual interaction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rodin, Vadim; Faessler, Amand

2011-07-15

In the present work the sensitivity of calculated {beta}{beta}-decay amplitudes to a realistic residual interaction is analyzed in the framework of the approach of O. A. Rumyantsev and M. H. Urin, Phys. Lett. B 443, 51 (1998). and V. A. Rodin, M. H. Urin, and A. Faessler, Nucl. Phys. A 747, 297 (2005). Both the Gamow-Teller (GT) and Fermi (F) matrix elements M{sup 2}{nu} for two-neutrino {beta}{beta} decay (2{nu}{beta}{beta} decay), along with the monopole transition contributions to the total matrix elements M{sup 0{nu}} of neutrinoless {beta}{beta} decay (0{nu}{beta}{beta} decay), are calculated within the quasiparticle random-phase approximation (QRPA). In the aforementionedmore » approach decompositions of M{sup 2{nu}} and M{sup 0{nu}} can be obtained in terms of the corresponding energy-weighted sum rules S. It is shown that in most of the cases almost the whole dependence of M{sup 2{nu}} and M{sup 0{nu}} on the particle-particle (p-p) renormalization parameter g{sub pp} is accounted for by the g{sub pp} dependence of the corresponding sum rules S. General expressions relating S to a realistic residual particle-particle interaction are derived, which show a pronounced sensitivity of S to the singlet-channel interaction in the case of F transitions and to the triplet-channel interaction in the case of GT transitions. Thus, the sensitivity of M{sup 2{nu}} and M{sup 0{nu}} to the SU(4)-symmetry-breaking part of the p-p residual interaction is dictated by the generic structure of the {beta}{beta}-decay amplitudes. Therefore, a choice of this part in a particular calculation needs a special caution. Finally, a better isospin-consistent way of renormalization of a realistic residual p-p interaction to use in QRPA calculations is suggested.« less

Increased expression of transforming growth factor beta s after acute oedematous pancreatitis in rats suggests a role in pancreatic repair.

PubMed Central

Riesle, E; Friess, H; Zhao, L; Wagner, M; Uhl, W; Baczako, K; Gold, L I; Korc, M; Büchler, M W

1997-01-01

BACKGROUND: Transforming growth factor beta isoforms (TGF beta s) belong to a family of multifunctional regulators of cellular growth and differentiation. They are mitogenic and chemotactic for fibroblasts and are potent stimulators of extracellular matrix production (collagen) and deposition. Upregulation of TGF beta transcription has been reported for several in vivo systems during repair after injury. AIMS: To study the expression of the three mammalian isoforms of TGF beta (TGF beta 1-3) and their relation to collagen expression as a marker for fibroblast response in acute oedematous pancreatitis in rats. METHODS: Using northern blot analysis and immunohistochemistry, the expression and localisation of TGF beta isoforms, collagen, and amylase were analysed during the course of acute oedematous pancreatitis in rats, experimentally induced by intravenous caerulein infusion. RESULTS: Induction of acute pancreatitis resulted in a biphasic peak pattern of expression of TGF beta 1, beta 2, and beta 3 mRNA, with a pronounced increase from day 1 to day 3 (sixfold, 2.5-fold, fivefold, respectively) and again from day 5 to day 7 (three-fold, 2.3-fold, 3.5-fold, respectively). The temporal changes in TGF beta mRNA identically paralleled the expression in collagen mRNA. In contrast, amylase mRNA expression, used as a general indicator of acinar cell integrity, was slightly decreased after induction of acute pancreatitis. Immunohistochemical analysis of pancreatitis tissue showed that increased expression of TGF beta s was mainly present in the pancreatic acinar and ductal cells; this was evident within one day after pancreatitis induction. CONCLUSION: Overexpression of TGF beta s after induction of acute pancreatitis suggests a role for these proteins in pancreatic repair and remodelling. The increased levels of TGF beta s may help suppress immune activation, and may contribute to the increase in the extracellular matrix including collagen and to the repair of the pancreatic parenchyma. Images PMID:9155579

Species-specific vesicular monoamine transporter 2 (VMAT2) expression in mammalian pancreatic beta cells: implications for optimising radioligand-based human beta cell mass (BCM) imaging in animal models

PubMed Central

Hartwig, N. R.; Kalmbach, N.; Klietz, M.; Anlauf, M.; Eiden, L. E.; Weihe, E.

2014-01-01

Aims/hypothesis Imaging of beta cell mass (BCM) is a major challenge in diabetes research. The vesicular monoamine transporter 2 (VMAT2) is abundantly expressed in human beta cells. Radiolabelled analogues of tetrabenazine (TBZ; a low-molecular-weight, cell-permeant VMAT2-selective ligand) have been employed for pancreatic islet imaging in humans. Since reports on TBZ-based VMAT2 imaging in rodent pancreas have been fraught with confusion, we compared VMAT2 gene expression patterns in the mouse, rat, pig and human pancreas, to identify appropriate animal models with which to further validate and optimise TBZ imaging in humans. Methods We used a panel of highly sensitive VMAT2 antibodies developed against equivalently antigenic regions of the transporter from each species in combination with immunostaining for insulin and species-specific in situ hybridisation probes. Individual pancreatic islets were obtained by laser-capture microdissection and subjected to analysis of mRNA expression of VMAT2. Results The VMAT2 protein was not expressed in beta cells in the adult pancreas of common mouse or rat laboratory strains, in contrast to its expression in beta cells (but not other pancreatic endocrine cell types) in the pancreas of pigs and humans. VMAT2- and tyrosine hydroxylase co-positive (catecholaminergic) innervation was less abundant in humans than in rodents. VMAT2-positive mast cells were identified in the pancreas of all species. Conclusions/interpretation Primates and pigs are suitable models for TBZ imaging of beta cells. Rodents, because of a complete lack of VMAT2 expression in the endocrine pancreas, are a ‘null’ model for assessing interference with BCM measurements by VMAT2-positive mast cells and sympathetic innervation in the pancreas. PMID:23404442

Numerical study of a multigrid method with four smoothing methods for the incompressible Navier-Stokes equations in general coordinates

NASA Technical Reports Server (NTRS)

Zeng, S.; Wesseling, P.

1993-01-01

The performance of a linear multigrid method using four smoothing methods, called SCGS (Symmetrical Coupled GauBeta-Seidel), CLGS (Collective Line GauBeta-Seidel), SILU (Scalar ILU), and CILU (Collective ILU), is investigated for the incompressible Navier-Stokes equations in general coordinates, in association with Galerkin coarse grid approximation. Robustness and efficiency are measured and compared by application to test problems. The numerical results show that CILU is the most robust, SILU the least, with CLGS and SCGS in between. CLGS is the best in efficiency, SCGS and CILU follow, and SILU is the worst.

On the Empirical Importance of the Conditional Skewness Assumption in Modelling the Relationship between Risk and Return

NASA Astrophysics Data System (ADS)

Pipień, M.

2008-09-01

We present the results of an application of Bayesian inference in testing the relation between risk and return on the financial instruments. On the basis of the Intertemporal Capital Asset Pricing Model, proposed by Merton we built a general sampling distribution suitable in analysing this relationship. The most important feature of our assumptions is that the skewness of the conditional distribution of returns is used as an alternative source of relation between risk and return. This general specification relates to Skewed Generalized Autoregressive Conditionally Heteroscedastic-in-Mean model. In order to make conditional distribution of financial returns skewed we considered the unified approach based on the inverse probability integral transformation. In particular, we applied hidden truncation mechanism, inverse scale factors, order statistics concept, Beta and Bernstein distribution transformations and also a constructive method. Based on the daily excess returns on the Warsaw Stock Exchange Index we checked the empirical importance of the conditional skewness assumption on the relation between risk and return on the Warsaw Stock Market. We present posterior probabilities of all competing specifications as well as the posterior analysis of the positive sign of the tested relationship.

Neutrino Mass Bounds from 0{nu}{beta}{beta} Decays and Large Scale Structures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Keum, Y.-Y.; Department of Physics, National Taiwan University, Taipei, Taiwan 10672; Ichiki, K.

2008-05-21

We investigate the way how the total mass sum of neutrinos can be constrained from the neutrinoless double beta decay and cosmological probes with cosmic microwave background (WMAP 3-year results), large scale structures including 2dFGRS and SDSS data sets. First we discuss, in brief, on the current status of neutrino mass bounds from neutrino beta decays and cosmic constrain within the flat {lambda}CMD model. In addition, we explore the interacting neutrino dark-energy model, where the evolution of neutrino masses is determined by quintessence scalar filed, which is responsable for cosmic acceleration today. Assuming the flatness of the universe, the constraintmore » we can derive from the current observation is {sigma}m{sub {nu}}<0.87 eV at the 95% confidence level, which is consistent with {sigma}m{sub {nu}}<0.68 eV in the flat {lambda}CDM model.« less

Setting limits on q0 from gravitational lensing

NASA Technical Reports Server (NTRS)

Gott, J. Richard, III; Park, Myeong-Gu; Lee, Hyung Mok

1989-01-01

Gravitational lensing by galaxies in a wide variety of cosmological models is considered. For closed models, the lensing depends on the parameter beta(crit). If beta(crit) is greater than zero, a normal lensing case can be obtained with two bright images separated by an angle twice beta(crit) and a third, arbitrarily dim image between them coincident with the position of the lensing galaxy nucleus. As the QSO approaches the antipodal redshift, which can occur in models with large values of the cosmological constant, the cross sections for lensing blow up. An overfocused case where beta(crit) is less than zero can be obtained for a QSO beyond the antipodal redshift. In this case, when a lensing event occurs, only one arbitrarily dim image coincident with the position of the lensing galaxy nucleus is seen. If galaxy rotation curves are always flat or slowly rising, the overfocused case always produces one image.

Spin Polarization of Mg-23 in Mg-24 + Au, Cu and Al Collisions at 91 A MeV

NASA Technical Reports Server (NTRS)

Matsuta, K.; Fukuda, S.; Izumikawa, T.; Tanigaki, M.; Fukuda, M.; Nakazato, M.; Mihara, M.; Onishi, T.; Yamaguchi, T.; Miyake, T.

1994-01-01

Spin polarization of beta-emitting fragment Mg-23(I(sup pi) = 3/2(sup +), T(sub 1/2 = l1.3 s) produced through the projectile fragmentation process in Mg-24 + Au, Cu and Al collisions has been observed at 91 AMeV. General trend in the observed momentum dependence of polarization is reproduced well qualitatively by a simple fragmentation model based on the participant-spectator picture, for heavy and light targets. However the polarization behavior differs from this model in tern of zero crossing momentum, which become prominent in the case of Cu target, where the polarization is not monotone function of the fragment momentum.

Vibrational and chiroptical spectroscopic characterization of gamma-turn model cyclic tetrapeptides containing two beta-Ala residues.

PubMed

Vass, Elemér; Majer, Zsuzsa; Kohalmy, Krisztina; Hollósi, Miklós

2010-08-01

The optical spectroscopic characterization of gamma-turns in solution is uncertain and their distinction from beta-turns is often difficult. This work reports systematic ECD and vibrational circular dichroism (VCD) spectroscopic studies on gamma-turn model cyclic tetrapeptides cyclo(Ala-beta-Ala-Pro-beta-Ala) (1), cyclo(Pro-beta-Ala-Pro-beta-Ala) (2) and cyclo(Ala-beta-Ala-Ala-beta-Ala) (3). Conformational analysis performed at the 6-31G(d)/B3LYP level of theory using an adequate PCM solvent model predicted one predominant conformer for 1-3, featuring two inverse gamma-turns. The ECD spectra in ACN of 1 and 2 are characterized by a negative n-->pi* band near 230 nm and a positive pi-->pi* band below 200 nm with a long wavelength shoulder. The ECD spectra in TFE of 1-3 show similar spectra with blue-shifted bands. The VCD spectra in ACN-d(3) of 1 and 2 show a +/-/+/- amide I sign pattern resulting from four uncoupled vibrations in the case of 1 and a sequence of two positive couplets in the case of 2. A -/+/+/- amide I VCD pattern was measured for 3 in TFE-d(2). All three peptides give a positive couplet or couplet-like feature (+/-) in the amide II region. VCD spectroscopy, in agreement with theoretical calculations revealed that low frequency amide I vibrations (at approximately 1630 cm(-1) or below) are indicative of a C(7) H-bonded inverse gamma-turns with Pro in position 2, while gamma-turns encompassing Ala absorb at higher frequency (above 1645 cm(-1)). Copyright 2010 Wiley-Liss, Inc.

SU-E-J-03: A Comprehensive Comparison Between Alpha and Beta Emitters for Cancer Radioimmunotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang, C.Y.; Guatelli, S; Oborn, B

2014-06-01

Purpose: The purpose of this study is to perform a comprehensive comparison of the therapeutic efficacy and cytotoxicity of alpha and beta emitters for Radioimmunotherapy (RIT). For each stage of cancer development, specific models were built for the separate objectives of RIT to be addressed:a) kill isolated cancer cells in transit in the lymphatic and vascular circulation,b) regress avascular cell clusters,c) regress tumor vasculature and tumors. Methods: Because of the nature of short range, high LET alpha and long energy beta radiation and heterogeneous antigen expression among cancer cells, the microdosimetric approach is essential for the RIT assessment. Geant4 basedmore » microdosimetric models are developed for the three different stages of cancer progression: cancer cells, cell clusters and tumors. The energy deposition, specific energy resulted from different source distribution in the three models was calculated separately for 4 alpha emitting radioisotopes ({sup 211}At, {sup 213}Bi, {sup 223}Ra and {sup 225}Ac) and 6 beta emitters ({sup 32}P, {sup 33}P, {sup 67}Cu, {sup 90}Y, {sup 131}I and {sup 177}Lu). The cell survival, therapeutic efficacy and cytotoxicity are determined and compared between alpha and beta emitters. Results: We show that internal targeted alpha radiation has advantages over beta radiation for killing isolated cancer cells, regressing small cell clusters and also solid tumors. Alpha particles have much higher dose specificity and potency than beta particles. They can deposit 3 logs more dose than beta emitters to single cells and solid tumor. Tumor control probability relies on deep penetration of radioisotopes to cancer cell clusters and solid tumors. Conclusion: The results of this study provide a quantitative understanding of the efficacy and cytotoxicity of RIT for each stage of cancer development.« less

The role of glycogen synthase kinase 3 beta in brain injury induced by myocardial ischemia/reperfusion injury in a rat model of diabetes mellitus.

PubMed

Zhao, Bo; Gao, Wen-Wei; Liu, Ya-Jing; Jiang, Meng; Liu, Lian; Yuan, Quan; Hou, Jia-Bao; Xia, Zhong-Yuan

2017-10-01

Myocardial ischemia/reperfusion injury can lead to severe brain injury. Glycogen synthase kinase 3 beta is known to be involved in myo-cardial ischemia/reperfusion injury and diabetes mellitus. However, the precise role of glycogen synthase kinase 3 beta in myocardial ischemia/reperfusion injury-induced brain injury is unclear. In this study, we observed the effects of glycogen synthase kinase 3 beta on brain injury induced by myocardial ischemia/reperfusion injury in diabetic rats. Rat models of diabetes mellitus were generated via intraperitoneal injection of streptozotocin. Models of myocardial ischemia/reperfusion injury were generated by occluding the anterior descending branch of the left coronary artery. Post-conditioning comprised three cycles of ischemia/reperfusion. Immunohistochemical staining and western blot assays demonstrated that after 48 hours of reperfusion, the structure of the brain was seriously damaged in the experimental rats compared with normal controls. Expression of Bax, interleukin-6, interleukin-8, terminal deoxynucleotidyl transferase dUTP nick end labeling, and cleaved caspase-3 in the brain was significantly increased, while expression of Bcl-2, interleukin-10, and phospho-glycogen synthase kinase 3 beta was decreased. Diabetes mellitus can aggravate inflammatory reactions and apoptosis. Ischemic post-conditioning with glycogen synthase kinase 3 beta inhibitor lithium chloride can effectively reverse these changes. Our results showed that myocardial ischemic post-conditioning attenuated myocardial ischemia/reperfusion injury-induced brain injury by activating glyco-gen synthase kinase 3 beta. According to these results, glycogen synthase kinase 3 beta appears to be an important factor in brain injury induced by myocardial ischemia/reperfusion injury.

Chronic discrimination and bodily pain in a multiethnic cohort of midlife women in the Study of Women's Health Across the Nation.

PubMed

Dugan, Sheila A; Lewis, Tené T; Everson-Rose, Susan A; Jacobs, Elizabeth A; Harlow, Siobán D; Janssen, Imke

2017-09-01

A growing literature links discrimination to key markers of biobehavioral health. While racial or ethnic differences in pain are seen in experimental and clinical studies, the authors were interested in how chronic discrimination contributes to pain within multiple racial or ethnic groups over time. Participants were 3056 African American, Caucasian, Chinese, Hispanic, and Japanese women from the Study of Women's Health Across the Nation. The Everyday Discrimination Scale was assessed from baseline through 13 follow-up examinations. The bodily pain subscale of the MOS 36-Item Short-Form Health Survey (SF-36) was assessed annually. There were large racial or ethnic differences in reports of discrimination and pain. Discrimination attributions also varied by race or ethnicity. In linear mixed model analyses, initially adjusted for age, education, and pain medications, chronic everyday discrimination was associated with more bodily pain in all ethnic groups (beta = -5.84; P < 0.002 for Japanese; beta = -6.17; P < 0.001 for African American; beta = -8.74; P < 0.001 for Chinese; beta = -10.54; P < 0.001 for Caucasians; beta = -12.82; P < 0.001 for Hispanic). Associations remained significant in all ethnic groups after adjusting for additional covariates in subsequent models until adding depressive symptoms as covariate; in the final fully-adjusted models, discrimination remained a significant predictor of pain for African American (beta = -4.50; P < 0.001), Chinese (beta = -6.62; P < 0.001), and Caucasian (beta = -7.86; P < 0.001) women. In this longitudinal study, experiences of everyday discrimination were strongly linked to reports of bodily pain for the majority of women. Further research is needed to determine if addressing psychosocial stressors, such as discrimination, with patients can enhance clinical management of pain symptoms.

A multilaboratory peer assessment quality assurance program-based evaluation of anticardiolipin antibody, and beta2-glycoprotein I antibody testing.

PubMed

Favaloro, Emmanuel J; Wong, Richard C W; Silvestrini, Roger; McEvoy, Robert; Jovanovich, Susan; Roberts-Thomson, Peter

2005-02-01

We evaluated the performance of anticardiolipin (aCL) and beta2-glycoprotein I (beta2-GPI) antibody assays through a large external quality assurance program. Data from the 2002 cycle of the Royal College of Pathologists of Australasia Quality Assurance Program (RCPA QAP) were analyzed for variation in reported numerical values and semiquantitative results or interpretations according to method type or group and in conjunction with available clinical data. High interlaboratory variation in numerical results and notable method-based variation, combined with a general lack of consensus in semiquantitative reporting, continues to be observed. Numerical results from cross-laboratory testing of 12 serum samples (for immunoglobulin G [IgG]-aCL, IgM-aCL, and IgG-beta2-GPI) yielded interlaboratory coefficients of variation (CVs) that were higher than 50% in six of 12 (50%) specimens for IgG-aCL, and 12 of 12 (100%) specimens for IgM-aCL and IgG-beta2-GPI. Semiquantitative reporting also varied considerably, with total (100%) consensus occurring in only four of 36 (11%) occasions. General consensus (where > 90% of participating laboratories agreed that a given serum sample gave a result of either negative or positive) was only obtained on 13 of 36 (36%) occasions. Variation in results between different method types or groups were also present, resulting in potential biasing of the RCPA QAP-defined target results by the large number of laboratories using the dominant aCL assays. Finally, laboratory findings frequently did not agree with the available clinical information. In conclusion, in a large proportion of specimens from the 2002 RCPA QAP cycle, laboratories could not agree on whether a serum sample tested was aCL-positive or aCL-negative, or beta2-GPI-positive or beta2-GPI-negative. Despite prior attempts to improve the standardization of testing and reporting practices, laboratory testing for aCL and anti-beta2-GPI still demonstrates significant interlaboratory and intermethod variation, which needs to be taken into account for the clinical interpretation of test results, especially those from different laboratories.

Improvement in the accuracy of back trajectories using WRF to identify pollen sources in southern Iberian Peninsula.

PubMed

Hernández-Ceballos, M A; Skjøth, C A; García-Mozo, H; Bolívar, J P; Galán, C

2014-12-01

Airborne pollen transport at micro-, meso-gamma and meso-beta scales must be studied by atmospheric models, having special relevance in complex terrain. In these cases, the accuracy of these models is mainly determined by the spatial resolution of the underlying meteorological dataset. This work examines how meteorological datasets determine the results obtained from atmospheric transport models used to describe pollen transport in the atmosphere. We investigate the effect of the spatial resolution when computing backward trajectories with the HYSPLIT model. We have used meteorological datasets from the WRF model with 27, 9 and 3 km resolutions and from the GDAS files with 1° resolution. This work allows characterizing atmospheric transport of Olea pollen in a region with complex flows. The results show that the complex terrain affects the trajectories and this effect varies with the different meteorological datasets. Overall, the change from GDAS to WRF-ARW inputs improves the analyses with the HYSPLIT model, thereby increasing the understanding the pollen episode. The results indicate that a spatial resolution of at least 9 km is needed to simulate atmospheric flows that are considerable affected by the relief of the landscape. The results suggest that the appropriate meteorological files should be considered when atmospheric models are used to characterize the atmospheric transport of pollen on micro-, meso-gamma and meso-beta scales. Furthermore, at these scales, the results are believed to be generally applicable for related areas such as the description of atmospheric transport of radionuclides or in the definition of nuclear-radioactivity emergency preparedness.

QSAR modeling of β-lactam binding to human serum proteins

NASA Astrophysics Data System (ADS)

Hall, L. Mark; Hall, Lowell H.; Kier, Lemont B.

2003-02-01

The binding of beta-lactams to human serum proteins was modeled with topological descriptors of molecular structure. Experimental data was the concentration of protein-bound drug expressed as a percent of the total plasma concentration (percent fraction bound, PFB) for 87 penicillins and for 115 β-lactams. The electrotopological state indices (E-State) and the molecular connectivity chi indices were found to be the basis of two satisfactory models. A data set of 74 penicillins from a drug design series was successfully modeled with statistics: r2=0.80, s = 12.1, q2=0.76, spress=13.4. This model was then used to predict protein binding (PFB) for 13 commercial penicillins, resulting in a very good mean absolute error, MAE = 12.7 and correlation coefficient, q2=0.84. A group of 28 cephalosporins were combined with the penicillin data to create a dataset of 115 beta-lactams that was successfully modeled: r2=0.82, s = 12.7, q2=0.78, spress=13.7. A ten-fold 10% leave-group-out (LGO) cross-validation procedure was implemented, leading to very good statistics: MAE = 10.9, spress=14.0, q2 (or r2 press)=0.78. The models indicate a combination of general and specific structure features that are important for estimating protein binding in this class of antibiotics. For the β-lactams, significant factors that increase binding are presence and electron accessibility of aromatic rings, halogens, methylene groups, and =N- atoms. Significant negative influence on binding comes from amine groups and carbonyl oxygen atoms.

Improvement in the accuracy of back trajectories using WRF to identify pollen sources in southern Iberian Peninsula

NASA Astrophysics Data System (ADS)

Hernández-Ceballos, M. A.; Skjøth, C. A.; García-Mozo, H.; Bolívar, J. P.; Galán, C.

2014-12-01

Airborne pollen transport at micro-, meso-gamma and meso-beta scales must be studied by atmospheric models, having special relevance in complex terrain. In these cases, the accuracy of these models is mainly determined by the spatial resolution of the underlying meteorological dataset. This work examines how meteorological datasets determine the results obtained from atmospheric transport models used to describe pollen transport in the atmosphere. We investigate the effect of the spatial resolution when computing backward trajectories with the HYSPLIT model. We have used meteorological datasets from the WRF model with 27, 9 and 3 km resolutions and from the GDAS files with 1 ° resolution. This work allows characterizing atmospheric transport of Olea pollen in a region with complex flows. The results show that the complex terrain affects the trajectories and this effect varies with the different meteorological datasets. Overall, the change from GDAS to WRF-ARW inputs improves the analyses with the HYSPLIT model, thereby increasing the understanding the pollen episode. The results indicate that a spatial resolution of at least 9 km is needed to simulate atmospheric flows that are considerable affected by the relief of the landscape. The results suggest that the appropriate meteorological files should be considered when atmospheric models are used to characterize the atmospheric transport of pollen on micro-, meso-gamma and meso-beta scales. Furthermore, at these scales, the results are believed to be generally applicable for related areas such as the description of atmospheric transport of radionuclides or in the definition of nuclear-radioactivity emergency preparedness.

Meprin A and meprin {alpha} generate biologically functional IL-1{beta} from pro-IL-1{beta}

DOE Office of Scientific and Technical Information (OSTI.GOV)

Herzog, Christian; University of Arkansas for Medical Sciences, Department of Medicine, Little Rock, AR 72205; Haun, Randy S.

The present study demonstrates that both oligomeric metalloendopeptidase meprin A purified from kidney cortex and recombinant meprin {alpha} are capable of generating biologically active IL-1{beta} from its precursor pro-IL-1{beta}. Amino-acid sequencing analysis reveals that meprin A and meprin {alpha} cleave pro-IL-1{beta} at the His{sup 115}-Asp{sup 116} bond, which is one amino acid N-terminal to the caspase-1 cleavage site and five amino acids C-terminal to the meprin {beta} site. The biological activity of the pro-IL-1{beta} cleaved product produced by meprin A, determined by proliferative response of helper T-cells, was 3-fold higher to that of the IL-1{beta} product produced by meprin {beta}more » or caspase-1. In a mouse model of sepsis induced by cecal ligation puncture that results in elevated levels of serum IL-1{beta}, meprin inhibitor actinonin significantly reduces levels of serum IL-1{beta}. Meprin A and meprin {alpha} may therefore play a critical role in the production of active IL-1{beta} during inflammation and tissue injury.« less

In silico study of full-length amyloid beta 1-42 tri- and penta-oligomers in solution.

PubMed

Masman, Marcelo F; Eisel, Ulrich L M; Csizmadia, Imre G; Penke, Botond; Enriz, Ricardo D; Marrink, Siewert Jan; Luiten, Paul G M

2009-08-27

Amyloid oligomers are considered to play causal roles in the pathogenesis of amyloid-related degenerative diseases including Alzheimer's disease. Using MD simulation techniques, we explored the contributions of the different structural elements of trimeric and pentameric full-length Abeta1-42 aggregates in solution to their stability and conformational dynamics. We found that our models are stable at a temperature of 310 K, and converge toward an interdigitated side-chain packing for intermolecular contacts within the two beta-sheet regions of the aggregates: beta1 (residues 18-26) and beta2 (residues 31-42). MD simulations reveal that the beta-strand twist is a characteristic element of Abeta-aggregates, permitting a compact, interdigitated packing of side chains from neighboring beta-sheets. The beta2 portion formed a tightly organized beta-helix, whereas the beta1 portion did not show such a firm structural organization, although it maintained its beta-sheet conformation. Our simulations indicate that the hydrophobic core comprising the beta2 portion of the aggregate is a crucial stabilizing element in the Abeta aggregation process. On the basis of these structure-stability findings, the beta2 portion emerges as an optimal target for further antiamyloid drug design.

Selective stimulation and blockade of beta-adrenergic receptors in the mandibular gland of the red kangaroo, Macropus rufus.

PubMed

Beal, A M

2000-12-01

Intracarotid infusions of noradrenaline (0.15 nmol x kg(-1) x min(-1)) either alone or accompanied by phentolamine (1.5 nmol x kg(-1) x min(-1)) caused similar-sized increases in salivary protein, magnesium and bicarbonate, and decreases in osmolality, sodium, potassium and chloride whereas intravenous noradrenaline stimulated much smaller responses. Concurrent infusions of the beta1-antagonist, CGP20712A, blocked these noradrenaline-induced changes in salivary composition more effectively than equimolar infusions of the beta2-antagonist, ICI118551, thereby confirming the presence of beta1-adrenoceptors. Intracarotid infusion of salbutamol at 0.15, 0.3 and 1.5 nmol x kg(-1) x min(-1) caused increasing but qualitatively similar changes in salivary composition, sodium excepted, to intracarotid noradrenaline with 0.3 nmol being most similar quantitatively. Intravenous infusion of salbutamol caused larger changes in salivary composition than equimolar intravenous noradrenaline thereby indicating that the response to salbutamol may, in part, be mediated by reflex increases in general sympathetic tone triggered by lowered blood pressure. Eliminating this hypotensive effect by concurrent intravenous and intracarotid infusions of beta1-(CGP or atenolol) and beta2-(ICII18551) antagonists with intracarotid salbutamol showed that IC1118551 was more potent than the beta1-antagonists thereby demonstrating the presence of beta2-receptors. It was concluded that the kangaroo mandibular has functional beta1- and beta2-adrenoceptor subtypes in both endpieces and excurrent ducts and that the duct system has two populations of cells, each expressing one receptor subtype.

ALK and TGF-Beta Resistance in Breast Cancer

DTIC Science & Technology

2017-10-01

and H.F. Lodish, Role of transforming growth factor beta in human disease. N Engl J Med, 2000. 342(18): p. 1350-8. 3. Massague, J., S.W. Blain, and... Transforming growth factor-beta signaling in normal and malignant hematopoiesis. Leukemia, 2003. 17(9): p. 1731-7. 5. Lehman, H.L., et al., Modeling and

Pulsational mode-typing in line profile variables. I - Four Beta Cephei stars

NASA Technical Reports Server (NTRS)

Campos, A. J.; Smith, M. A.

1980-01-01

The detailed variations of line profiles in the Beta Cephei-type variable stars Gamma Pegasi, Beta Cephei, Delta Ceti and Sigma Scorpii are modeled throughout their pulsation cycles in order to classify the dominant pulsation mode as radial or nonradial. High-dispersion Reticon observations of the variables were obtained for the Si III line at 4567 A, and line profiles broadened by radial or nonradial pulsations, rotation and radial-tangential macroturbulence were calculated based on a model atmosphere. It is found that only a radial pulsation mode can reproduce the radial velocity amplitude, changes in line asymmetry and uniform line width observed in all four stars. Results are in agreement with the color-to-light arguments of Stamford and Watson (1978), and suggest that radial pulsation plays the dominant role in the observed variations in most Beta Cephei stars. Evidence for shocks or moving shells is also found in visual line data for Sigma Scorpii and an ultraviolet line of Beta Cephei, together with evidence of smooth, secular period changes in Beta Cephei and Delta Ceti.

Time reversal violation in radiative beta decay: experimental plans

NASA Astrophysics Data System (ADS)

Behr, J. A.; McNeil, J.; Anholm, M.; Gorelov, A.; Melconian, D.; Ashery, D.

2017-01-01

Some explanations for the excess of matter over antimatter in the universe involve sources of time reversal violation (TRV) in addition to the one known in the standard model of particle physics. We plan to search for TRV in a correlation between the momenta of the beta, neutrino, and the radiative gamma sometimes emitted in nuclear beta decay. Correlations involving three (out of four) momenta are sensitive at lowest order to different TRV physics than observables involving spin, such as electric dipole moments and spin-polarized beta decay correlations. Such experiments have been done in radiative kaon decay, but not in systems involving the lightest generation of quarks. An explicit low-energy physics model being tested produces TRV effects in the Fermi beta decay of the neutron, tritium, or some positron-decaying isotopes. We will present plans to measure the TRV asymmetry in radiative beta decay of laser-trapped 38mK at better than 0.01 sensitivity, including suppression of background from positron annihilation. Supported by NSERC, D.O.E., Israel Science Foundation. TRIUMF receives federal funding via a contribution agreement with the National Research Council of Canada.

Activities of beta-lactam antibiotics against Escherichia coli strains producing extended-spectrum beta-lactamases.

PubMed Central

Jacoby, G A; Carreras, I

1990-01-01

Seven extended-spectrum beta-lactamases related to TEM and four enzymes derived from SHV-1 were transferred to a common Escherichia coli host so that the activity of a variety of beta-lactams could be tested in a uniform genetic environment. For most derivatives, penicillinase activity was 10% or less than that of strains making TEM-1, TEM-2, or SHV-1 beta-lactamase, suggesting that reduced catalytic efficiency accompanied the broader substrate spectrum. Despite this deficit, resistance to aztreonam, carumonam, cefdinir, cefepime, cefixime, cefmenoxime, cefotaxime, cefotiam, cefpirome, cefpodoxime, ceftazidime, ceftibuten, ceftizoxime, ceftriaxone, cefuroxime, and E1040 was enhanced. For strains producing TEM-type enzymes, however, MICs of carumonam, cefepime, cefmenoxime, cefotiam, cefpirome, and ceftibuten were 8 micrograms/ml or less. Susceptibilities of cefmetazole, cefotetan, cefoxitin, flomoxef, imipenem, meropenem, moxalactam, temocillin, FCE 22101, and Sch 34343 were unaffected. FCE 22101, imipenem, meropenem, and Sch 34343 were inhibitory for all strains at 1 microgram/ml or less. In E. coli an OmpF- porin mutation in combination with an extended-spectrum beta-lactamase enhanced resistance to many of these agents, but generally by only fourfold. Hyperproduction of chromosomal AmpC beta-lactamase increased resistance to 7-alpha-methoxy beta-lactams but not that to temocillin. When tested at 8 micrograms/ml, clavulanate was more potent than sulbactam or tazobactam in overcoming resistance to ampicillin, while cefoperazone-sulbactam was more active than ticarcillin-clavulanate or piperacillin-tazobactam, especially against TEM-type extended-spectrum beta-lactamases. PMID:2193623

Use of instrumental variables in the analysis of generalized linear models in the presence of unmeasured confounding with applications to epidemiological research.

PubMed

Johnston, K M; Gustafson, P; Levy, A R; Grootendorst, P

2008-04-30

A major, often unstated, concern of researchers carrying out epidemiological studies of medical therapy is the potential impact on validity if estimates of treatment are biased due to unmeasured confounders. One technique for obtaining consistent estimates of treatment effects in the presence of unmeasured confounders is instrumental variables analysis (IVA). This technique has been well developed in the econometrics literature and is being increasingly used in epidemiological studies. However, the approach to IVA that is most commonly used in such studies is based on linear models, while many epidemiological applications make use of non-linear models, specifically generalized linear models (GLMs) such as logistic or Poisson regression. Here we present a simple method for applying IVA within the class of GLMs using the generalized method of moments approach. We explore some of the theoretical properties of the method and illustrate its use within both a simulation example and an epidemiological study where unmeasured confounding is suspected to be present. We estimate the effects of beta-blocker therapy on one-year all-cause mortality after an incident hospitalization for heart failure, in the absence of data describing disease severity, which is believed to be a confounder. 2008 John Wiley & Sons, Ltd

Integrin-mediated transforming growth factor-beta activation regulates homeostasis of the pulmonary epithelial-mesenchymal trophic unit.

PubMed

Araya, Jun; Cambier, Stephanie; Morris, Alanna; Finkbeiner, Walter; Nishimura, Stephen L

2006-08-01

Trophic interactions between pulmonary epithelial and mesenchymal cell types, known as the epithelial-mesenchymal trophic unit (EMTU), are crucial in lung development and lung disease. Transforming growth factor (TGF)-beta is a key factor in mediating these interactions, but it is expressed in a latent form that requires activation to be functional. Using intact fetal tracheal tissue and primary cultures of fetal tracheal epithelial cells and fibroblasts, we demonstrate that a subset of integrins, alpha(v)beta(6) and alpha(v)beta(8), are responsible for almost all of the TGF-beta activation in the EMTU. Both alpha(v)beta(8) and alpha(v)beta(6) contribute to fetal tracheal epithelial activation of TGF-beta, whereas only alpha(v)beta(8) contributes to fetal tracheal fibroblast activation of TGF-beta. Interestingly, fetal tracheal epithelial alpha(v)beta(8)-mediated TGF-beta activation can be enhanced by phorbol esters, likely because of the increased activity of MT1-MMP, an essential co-factor in alpha(v)beta(8)-mediated activation of TGF-beta. Autocrine alpha(v)beta(8)-mediated TGF-beta activation by fetal tracheal fibroblasts results in suppression of both transcription and secretion of hepatocyte growth factor, which is sufficient to affect phosphorylation of the airway epithelial hepatocyte growth factor receptor, c-Met, as well as airway epithelial proliferation in a co-culture model of the EMTU. These findings elucidate the function and complex regulation of integrin-mediated activation of TGF-beta within the EMTU.

A recipe for designing water-soluble, beta-sheet-forming peptides.

PubMed Central

Mayo, K. H.; Ilyina, E.; Park, H.

1996-01-01

Based on observations of solubility and folding properties of peptide 33-mers derived from the beta-sheet domains of platelet factor-4 (PF4), interleukin-8 (IL-8), and growth related protein (Gro-alpha), as well as other beta-sheet-forming peptides, general guidelines have been developed to aid in the design of water soluble, self-association-induced beta-sheet-forming peptides. CD, 1H-NMR, and pulsed field gradient NMR self-diffusion measurements have been used to assess the degree of folding and state of aggregation. PF4 peptide forms native-like beta-sheet tetramers and is sparingly soluble above pH 6. IL-8 peptide is insoluble between pH 4.5 and pH 7.5, yet forms stable, native-like beta-sheet dimers at higher pH. Gro-alpha peptide is soluble at all pH values, yet displays no discernable beta-sheet structure even when diffusion data indicate dimer-tetramer aggregation. A recipe used in the de novo design of water-soluble beta-sheet-forming peptides calls for the peptide to contain 40-50% hydrophobic residues, usually aliphatic ones (I, L, V, A, M) (appropriately paired and mostly but not always alternating with polar residues in the sheet sequence), a positively charged (K, R) to negatively charged (E, D) residue ratio between 4/2 and 6/2, and a noncharged polar residue (N, Q, T, S) composition of about 20% or less. Results on four de novo designed, 33-residue peptides are presented supporting this approach. Under near physiologic conditions, all four peptides are soluble, form beta-sheet structures to varying degrees, and self-associate. One peptide folds as a stable, compact beta-sheet tetramer, whereas the others are transient beta-sheet-containing aggregates. PMID:8819163

Probing the N˜Z line via β decay

NASA Astrophysics Data System (ADS)

Oinonen, Markku

1999-11-01

This contribution reports several beta-decay studies performed at ISOLDE On-line Mass Separator at CERN recently for nuclei close to N=Z line. Beta decay of 58Zn provides a possibility to compare Gamow-Teller strength extracted from complementary beta-decay studies and charge-exchange reactions. Measurement on beta-decay half-life of 70Kr shows importance of experimental information in modelling the path of the astrophysical rp process. Decay of 71Kr is an example of a mirror beta decay and extends the systematics of these particular decays towards highly deformed region close to A=80.

Using support vector machine to predict beta- and gamma-turns in proteins.

PubMed

Hu, Xiuzhen; Li, Qianzhong

2008-09-01

By using the composite vector with increment of diversity, position conservation scoring function, and predictive secondary structures to express the information of sequence, a support vector machine (SVM) algorithm for predicting beta- and gamma-turns in the proteins is proposed. The 426 and 320 nonhomologous protein chains described by Guruprasad and Rajkumar (Guruprasad and Rajkumar J. Biosci 2000, 25,143) are used for training and testing the predictive model of the beta- and gamma-turns, respectively. The overall prediction accuracy and the Matthews correlation coefficient in 7-fold cross-validation are 79.8% and 0.47, respectively, for the beta-turns. The overall prediction accuracy in 5-fold cross-validation is 61.0% for the gamma-turns. These results are significantly higher than the other algorithms in the prediction of beta- and gamma-turns using the same datasets. In addition, the 547 and 823 nonhomologous protein chains described by Fuchs and Alix (Fuchs and Alix Proteins: Struct Funct Bioinform 2005, 59, 828) are used for training and testing the predictive model of the beta- and gamma-turns, and better results are obtained. This algorithm may be helpful to improve the performance of protein turns' prediction. To ensure the ability of the SVM method to correctly classify beta-turn and non-beta-turn (gamma-turn and non-gamma-turn), the receiver operating characteristic threshold independent measure curves are provided. (c) 2008 Wiley Periodicals, Inc.

Crystal Structure of Human [Beta]-Hexosaminidase B: Understanding the Molecular Basis of Sandhoff and Tay-Sachs Disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mark, Brian L.; Mahuran, Don J.; Cherney, Maia M.

2010-12-01

In humans, two major {beta}-hexosaminidase isoenzymes exist: Hex A and Hex B. Hex A is a heterodimer of subunits {alpha} and {beta} (60% identity), whereas Hex B is a homodimer of {beta}-subunits. Interest in human {beta}-hexosaminidase stems from its association with Tay-Sachs and Sandhoff disease; these are prototypical lysosomal storage disorders resulting from the abnormal accumulation of G{sub M2}-ganglioside (G{sub M2}). Hex A degrades G{sub M2} by removing a terminal N-acetyl-D-galactosamine ({beta}-GalNAc) residue, and this activity requires the G{sub M2}-activator, a protein which solubilizes the ganglioside for presentation to Hex A. We present here the crystal structure of human Hexmore » B, alone (2.4 {angstrom}) and in complex with the mechanistic inhibitors GalNAc-isofagomine (2.2 {angstrom}) or NAG-thiazoline (2.5 {angstrom}). From these, and the known X-ray structure of the G{sub M2}-activator, we have modeled Hex A in complex with the activator and ganglioside. Together, our crystallographic and modeling data demonstrate how {alpha} and {beta}-subunits dimerize to form either Hex A or Hex B, how these isoenzymes hydrolyze diverse substrates, and how many documented point mutations cause Sandhoff disease ({beta}-subunit mutations) and Tay-Sachs disease ({alpha}-subunit mutations).« less

Progress report on hot particle studies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baum, J.W.; Kaurin, D.G.; Waligorski, M.

1992-02-01

NCRP Report 106 on the effects of hot particles on the skin of pigs, monkeys, and humans was critically reviewed and reassessed. The analysis of the data of Forbes and Mikhail on the effects from activated UC{sub 2} particles, ranging in diameter from 144 {mu}m to 328 {mu}m, led to the formulation of a new model to predict both the threshold for acute ulceration and for ulcer diameter. In this model, a point dose of 27 Gy at a depth of 1.33 mm in tissue will cause an ulcer with a diameter determined by the radius to which this dosemore » extends. Application of the model to the Forbes and Mikhail data obtained with mixed fission product beta particles yielded a threshold'' (5% probability) of 6 {times} 10{sup 9} beta particles from a point source of high energy (2.25 MeV maximum) beta particles on skin. The above model was used to predict that approximately 1.2 {times} 10{sup 10} beta particles from Sr-Y-90 would produce similar effects, since few Sr-90 beta particles reach 1.33 mm depth. These emissions correspond to doses at 70-{mu}m depth in tissue of approximately 5.3 to 5.5 Gy averaged over 1 cm{sup 2}, respectively.« less

Progress report on hot particle studies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baum, J.W.; Kaurin, D.G.; Waligorski, M.

1992-02-01

NCRP Report 106 on the effects of hot particles on the skin of pigs, monkeys, and humans was critically reviewed and reassessed. The analysis of the data of Forbes and Mikhail on the effects from activated UC{sub 2} particles, ranging in diameter from 144 {mu}m to 328 {mu}m, led to the formulation of a new model to predict both the threshold for acute ulceration and for ulcer diameter. In this model, a point dose of 27 Gy at a depth of 1.33 mm in tissue will cause an ulcer with a diameter determined by the radius to which this dosemore » extends. Application of the model to the Forbes and Mikhail data obtained with mixed fission product beta particles yielded a ``threshold`` (5% probability) of 6 {times} 10{sup 9} beta particles from a point source of high energy (2.25 MeV maximum) beta particles on skin. The above model was used to predict that approximately 1.2 {times} 10{sup 10} beta particles from Sr-Y-90 would produce similar effects, since few Sr-90 beta particles reach 1.33 mm depth. These emissions correspond to doses at 70-{mu}m depth in tissue of approximately 5.3 to 5.5 Gy averaged over 1 cm{sup 2}, respectively.« less

On measures of association among genetic variables

PubMed Central

Gianola, Daniel; Manfredi, Eduardo; Simianer, Henner

2012-01-01

Summary Systems involving many variables are important in population and quantitative genetics, for example, in multi-trait prediction of breeding values and in exploration of multi-locus associations. We studied departures of the joint distribution of sets of genetic variables from independence. New measures of association based on notions of statistical distance between distributions are presented. These are more general than correlations, which are pairwise measures, and lack a clear interpretation beyond the bivariate normal distribution. Our measures are based on logarithmic (Kullback-Leibler) and on relative ‘distances’ between distributions. Indexes of association are developed and illustrated for quantitative genetics settings in which the joint distribution of the variables is either multivariate normal or multivariate-t, and we show how the indexes can be used to study linkage disequilibrium in a two-locus system with multiple alleles and present applications to systems of correlated beta distributions. Two multivariate beta and multivariate beta-binomial processes are examined, and new distributions are introduced: the GMS-Sarmanov multivariate beta and its beta-binomial counterpart. PMID:22742500

Protection from sunburn with beta-Carotene--a meta-analysis.

PubMed

Köpcke, Wolfgang; Krutmann, Jean

2008-01-01

Nutritional protection against skin damage from sunlight is increasingly advocated to the general public, but its effectiveness is controversial. In this meta-analysis, we have systematically reviewed the existing literature on human supplementation studies on dietary protection against sunburn by beta-carotene. A review of literature until June 2007 was performed in PubMed, ISI Web of Science and EBM Cochrane library and identified a total of seven studies which evaluated the effectiveness of beta-carotene in protection against sunburn. Data were abstracted from these studies by means of a standardized data collection protocol. The subsequent meta-analysis showed that (1) beta-carotene supplementation protects against sunburn and (2) the study duration had a significant influence on the effected size. Regression plot analysis revealed that protection required a minimum of 10 weeks of supplementation with a mean increase of the protective effect of 0.5 standard deviations with every additional month of supplementation. Thus, dietary supplementation of humans with beta-carotene provides protection against sunburn in a time-dependent manner.

75 FR 71532 - Airworthiness Directives; Robinson Helicopter Company (Robinson) Model R22, R22 Alpha, R22 Beta...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-24

... Airworthiness Directives; Robinson Helicopter Company (Robinson) Model R22, R22 Alpha, R22 Beta, and R22 Mariner... rule. SUMMARY: This amendment adopts a new airworthiness directive (AD) for Robinson Model R22, R22... Robinson Helicopter Company, 2901 Airport Drive, Torrance, California 90505, telephone (310) 539-0508, fax...

Occurrence of high-beta superthermal plasma events in the close environment of Jupiter's bow shock as observed by Ulysses

DOE Office of Scientific and Technical Information (OSTI.GOV)

Marhavilas, P. K.; Sarris, E. T.; Anagnostopoulos, G. C.

2011-01-04

The ratio of the plasma pressure to the magnetic field pressure (or of their energy densities) which is known as the plasma parameter 'beta'({beta}) has important implications to the propagation of energetic particles and the interaction of the solar wind with planetary magnetospheres. Although in the scientific literature the contribution of the superthermal particles to the plasma pressure is generally assumed negligible, we deduced, by analyzing energetic particles and magnetic field measurements recorded by the Ulysses spacecraft, that in a series of events, the energy density contained in the superthermal tail of the particle distribution is comparable to or evenmore » higher than the energy density of the magnetic field, creating conditions of high-beta plasma. More explicitly, in this paper we analyze Ulysses/HI-SCALE measurements of the energy density ratio (parameter {beta}{sub ep}) of the energetic ions'(20 keV to {approx}5 MeV) to the magnetic field's in order to find occurrences of high-beta ({beta}{sub ep}>1) superthermal plasma conditions in the environment of the Jovian magnetosphere, which is an interesting plasma laboratory and an important source of emissions in our solar system. In particular, we examine high-beta ion events close to Jupiter's bow shock, which are produced by two processes: (a) bow shock ion acceleration and (b) ion leakage from the magnetosphere.« less

Prenatal stress decreases glycogen synthase kinase-3 phosphorylation in the rat frontal cortex.

PubMed

Szymańska, Magdalena; Suska, Anna; Budziszewska, Bogusława; Jaworska-Feil, Lucylla; Basta-Kaim, Agnieszka; Leśkiewicz, Monika; Kubera, Marta; Gergont, Aleksandra; Kroczka, Sławomir; Kaciński, Marek; Lasoń, Władysław

2009-01-01

It has been postulated that hyperactive glycogen synthase kinase-3 (GSK-3) is an important factor in the pathogenesis of depression, and that this enzyme also contributes to the mechanism of antidepressant drug action. In the present study, we investigated the effect of prenatal stress (an animal model of depression) and long-term treatment with antidepressant drugs on the concentration of GSK-3beta and its main regulating protein kinase B (PKB, Akt). The concentration of GSK-3beta, its inactive form (phospho-Ser9-GSK-3beta), and the amounts of active (phospho-Akt) and total Akt were determined in the hippocampus and frontal cortex in rats. In order to verify our animal model of depression, immobility time in the forced swim test (Porsolt test) was also determined.We found that prenatally stressed rats display a high level of immobility in the Porsolt test and chronic treatment with imipramine, fluoxetine, mirtazapine and tianeptine normalize this change. Western blot analysis demonstrated that GSK-3beta levels were significantly elevated in the frontal cortex, but not in the hippocampus, of prenatally stressed rats. The concentration of its non-active form (phospho-Ser9-GSK-3beta) was decreased only in the former brain structure. No changes were found in the amounts of active (phospho-Akt) and total Akt in both studied brain structures. Chronic treatment with antidepressant drugs diminished stress-induced alterations in GSK-3beta and phospho-GSK-3beta the frontal cortex, but had no effect on the concentration of these enzymes in the hippocampus. Moreover, levels of Akt and phospho-Akt in all experimental groups remained unchanged. Since our animal model of depression is connected with hyperactivity of the HPA axis, our results suggest that GSK-3beta is an important intracellular target for maladaptive glucocorticoid action on frontal cortex neurons and in antidepressant drug effects. Furthermore, the influence of stress and antidepressant drugs on GSK-3beta does not appear to impact the kinase activity of Akt.

Inhibitory effects of hepatocyte growth factor and interleukin-6 on transforming growth factor-beta1 mediated vocal fold fibroblast-myofibroblast differentiation.

PubMed

Vyas, Bimal; Ishikawa, Keiko; Duflo, Suzy; Chen, Xia; Thibeault, Susan L

2010-05-01

The role of myofibroblasts in vocal fold scarring has not been extensively studied, partly because of the lack of a robust in vitro model. The objective of this investigation was to develop and characterize a myofibroblast in vitro model that could be utilized to investigate the molecular mechanism of myofibroblast differentiation and function in injured vocal fold tissue. Differentiation of human primary vocal fold fibroblasts (hVFFs) to myofibroblasts was stimulated with 5, 10, or 20 ng/mL of recombinant transforming growth factor-beta1 (TGF-beta1). Cultures were analyzed by immunofluorescence and Western blotting, with an alpha-smooth muscle actin (alpha-SMA) antibody used as a myofibroblast marker. Normal rabbit vocal folds were treated with 10 ng/mL of TGF-beta1 for 7 days for in vivo corroboration. The effects of interleukin-6 (IL-6) and hepatocyte growth factor (HGF) on myofibroblast differentiation were studied with Western blots. The hVFFs demonstrated positive alpha-SMA labeling in cells stimulated by 10 and 20 ng/mL TGF-beta1, indicating that hVFFs were capable of differentiation to myofibroblasts. Transforming growth factor-beta1 induced the largest increase in alpha-SMA at 10 ng/mL on day 5 of treatment. Both HGF and IL-6 suppressed the expression of TGF-beta1-induced alpha-SMA. Our work characterizes a useful in vitro model of TGF-beta1-mediated vocal fold fibroblast-myofibroblast differentiation. The extent of differentiation appears to be attenuated by HGF, suggesting a potential mechanism to support prior work indicating that HGF plays a protective role in reducing scar formation in vocal fold injuries. Paradoxically, IL-6, which has been shown to play a profibrotic role in dermal studies, also attenuated the TGF-beta1 response.

Negative allosteric modulators that target human alpha4beta2 neuronal nicotinic receptors.

PubMed

Henderson, Brandon J; Pavlovicz, Ryan E; Allen, Jerad D; González-Cestari, Tatiana F; Orac, Crina M; Bonnell, Andrew B; Zhu, Michael X; Boyd, R Thomas; Li, Chenglong; Bergmeier, Stephen C; McKay, Dennis B

2010-09-01

Allosteric modulation of neuronal nicotinic acetylcholine receptors (nAChRs) is considered to be one of the most promising approaches for therapeutics. We have previously reported on the pharmacological activity of several compounds that act as negative allosteric modulators (NAMs) of nAChRs. In the following studies, the effects of 30 NAMs from our small chemical library on both human alpha4beta2 (Halpha4beta2) and human alpha3beta4 (Halpha3beta4) nAChRs expressed in human embryonic kidney ts201 cells were investigated. During calcium accumulation assays, these NAMs inhibited nAChR activation with IC(50) values ranging from 2.4 microM to more than 100 microM. Several NAMs showed relative selectivity for Halpha4beta2 nAChRs with IC(50) values in the low micromolar range. A lead molecule, KAB-18, was identified that shows relative selectivity for Halpha4beta2 nAChRs. This molecule contains three phenyl rings, one piperidine ring, and one ester bond linkage. Structure-activity relationship (SAR) analyses of our data revealed three regions of KAB-18 that contribute to its relative selectivity. Predictive three-dimensional quantitative SAR (comparative molecular field analysis and comparative molecular similarity indices analysis) models were generated from these data, and a pharmacophore model was constructed to determine the chemical features that are important for biological activity. Using docking approaches and molecular dynamics on a Halpha4beta2 nAChR homology model, a binding mode for KAB-18 at the alpha/beta subunit interface that corresponds to the predicted pharmacophore is described. This binding mode was supported by mutagenesis studies. In summary, these studies highlight the importance of SAR, computational, and molecular biology approaches for the design and synthesis of potent and selective antagonists targeting specific nAChR subtypes.

A Quantitative Tunneling/Desorption Model for the Exchange Current at the Porous Electrode/Beta - Alumina/Alkali Metal Gas Three Phase Zone at 700-1300K

NASA Technical Reports Server (NTRS)

Williams, R. M.; Ryan, M. A.; Saipetch, C.; LeDuc, H. G.

1996-01-01

The exchange current observed at porous metal electrodes on sodium or potassium beta -alumina solid electrolytes in alkali metal vapor is quantitatively modeled with a multi-step process with good agreement with experimental results.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lopez-Ruiz, R.; Nagy, A.; Romera, E.

A two-parameter family of complexity measures C-tilde{sup ({alpha},{beta})} based on the Renyi entropies is introduced and characterized by a detailed study of its mathematical properties. This family is the generalization of a continuous version of the Lopez-Ruiz-Mancini-Calbet complexity, which is recovered for {alpha}=1 and {beta}=2. These complexity measures are obtained by multiplying two quantities bringing global information on the probability distribution defining the system. When one of the parameters, {alpha} or {beta}, goes to infinity, one of the global factors becomes a local factor. For this special case, the complexity is calculated on different quantum systems: H-atom, harmonic oscillator, andmore » square well.« less

Rematching AGS Booster synchrotron injection lattice for smaller transverse beam emittances

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, C.; Beebe-Wang, J.; Brown, K.

2017-01-25

The polarized proton beam is injected into the booster via the charge-exchange (H- to H+) scheme. The emittance growth due to scattering at the stripping foil is proportional to the beta functions at the foil. It was demonstrated that the current scheme of reducing the beta functions at the stripping foil preserves the emittance better; however the betatron tunes are above but very close to half integer. Due to concern of space charge and half integer in general, options of lattice designs aimed towards reducing the beta functions at the stripping foil with tunes at more favorable places are explored.

Urocortin 3 Marks Mature Human Primary and Embryonic Stem Cell-Derived Pancreatic Alpha and Beta Cells

PubMed Central

van der Meulen, Talitha; Xie, Ruiyu; Kelly, Olivia G.; Vale, Wylie W.; Sander, Maike; Huising, Mark O.

2012-01-01

The peptide hormone Urocortin 3 (Ucn 3) is abundantly and exclusively expressed in mouse pancreatic beta cells where it regulates insulin secretion. Here we demonstrate that Ucn 3 first appears at embryonic day (E) 17.5 and, from approximately postnatal day (p) 7 and onwards throughout adult life, becomes a unifying and exclusive feature of mouse beta cells. These observations identify Ucn 3 as a potential beta cell maturation marker. To determine whether Ucn 3 is similarly restricted to beta cells in humans, we conducted comprehensive immunohistochemistry and gene expression experiments on macaque and human pancreas and sorted primary human islet cells. This revealed that Ucn 3 is not restricted to the beta cell lineage in primates, but is also expressed in alpha cells. To substantiate these findings, we analyzed human embryonic stem cell (hESC)-derived pancreatic endoderm that differentiates into mature endocrine cells upon engraftment in mice. Ucn 3 expression in hESC-derived grafts increased robustly upon differentiation into mature endocrine cells and localized to both alpha and beta cells. Collectively, these observations confirm that Ucn 3 is expressed in adult beta cells in both mouse and human and appears late in beta cell differentiation. Expression of Pdx1, Nkx6.1 and PC1/3 in hESC-derived Ucn 3+ beta cells supports this. However, the expression of Ucn 3 in primary and hESC-derived alpha cells demonstrates that human Ucn 3 is not exclusive to the beta cell lineage but is a general marker for both the alpha and beta cell lineages. Ucn 3+ hESC-derived alpha cells do not express Nkx6.1, Pdx1 or PC1/3 in agreement with the presence of a separate population of Ucn 3+ alpha cells. Our study highlights important species differences in Ucn 3 expression, which have implications for its utility as a marker to identify mature beta cells in (re)programming strategies. PMID:23251699

Mixtures of beta distributions in models of the duration of a project affected by risk

NASA Astrophysics Data System (ADS)

Gładysz, Barbara; Kuchta, Dorota

2017-07-01

This article presents a method for timetabling a project affected by risk. The times required to carry out tasks are modelled using mixtures of beta distributions. The parameters of these beta distributions are given by experts: one corresponding to the duration of a task in stable conditions, with no risks materializing, and the other corresponding to the duration of a task in the case when risks do occur. Finally, a case study will be presented and analysed: the project of constructing a shopping mall in Poland.

Depression among Transgender Older adults: General and Minority Stress

PubMed Central

Hoy-Ellis, Charles P.; Fredriksen-Goldsen, Karen I.

2017-01-01

Objectives This study aims to (1) examine the direct and indirect effects internalized heterosexism, concealment of gender identity, and perceived general stress in association with depression among transgender older adults; and (2) to assess the relative contribution of each relationship. Methods Secondary analyses of data from a large community-based study of older sexual and gender minorities were conducted utilizing structural equation modeling with a subsample (n = 174) of transgender adults aged 50 to 86-years old. Results Disclosure of gender identity had no significant direct or indirect effects on either perceived general stress or depression. Internalized heterosexism did not have a direct effect on depression, but did have a significant indirect effect through perceived general stress. Finally, perceived general stress had an additional significant direct effect on depression, over and above internalized heterosexism. Total effect sizes appear to be considerable with standardized betas greater than 5.0. Conclusion Perceived general stress and internalized heterosexism independently and cumulatively have significant direct and indirect effects on depression among transgender older adults. Implications for depression among transgender older adults and the role of community psychology are discussed. PMID:28369987

Fragment and knowledge-based design of selective GSK-3beta inhibitors using virtual screening models.

PubMed

Vadivelan, S; Sinha, Barij Nayan; Tajne, Sunita; Jagarlapudi, Sarma A R P

2009-06-01

Glycogen Synthase Kinase 3beta is one of the important targets in the treatment of type II diabetes and Alzheimer's disease. Currently this target is in pursuit for type II diabetes and a few GSK-3beta inhibitors have been now advanced to Phases I and II of clinical trials. The best validated HypoGen model consists of four pharmacophore features; 1) two hydrogen bond acceptors, 2) one hydrogen bond donor and 3) one hydrophobic. This pharmacophore model correlates well with the docking model, one hydrogen bond acceptor is necessary for the H-bond interaction with VAL135, and second hydrogen bond acceptor is important for the H-bond interactions with ARG141 and the hydrophobic feature may be required for the weak H-bond interactions with ASP133. The comparative model was developed from analogue and structure-based models like Catalyst, Glide SP & XP, Gold Fitness & ChemScore and Ligand Fit using multiple linear regression analysis. A virtual library of 10,000 molecules was generated employing fragment and knowledge-based approach and the comparative model was used to predict the activities of these molecules. The H-bond with ARG141 appears to be unique to GSK-3beta and explains the high GSK-3beta selectivity observed for 1H-Quinazolin-4-ones and Benzo[e][1,3]oxazin-4-ones. This understanding of protein-ligand interactions and molecular recognition increases the rapid development of potent and selective inhibitors, and also helps to eliminate the increase in number of false positives and negatives.

[Effects of electroacupuncture of "Sanyinjiao" (SP 6) on contents of MDA and beta-EP, and expression of HSP 70 in the uterus in rats with dysmenorrhea].

PubMed

Song, Xiao-Lin; Zhang, Lu-Fen; Li, Xiao-Hong; Xu, Li-Li; Li, Chun-Hua; Ding, Xi-Yan; Ren, Xiao-Xuan; Zhao, Ya-Fang; Guo, Meng-Wei; Sun, Zhi-Fang; Zhu, Jiang

2010-10-01

To investigate the effect of electroacupuncture (EA) of "Sanyinjiao" (SP 6) on the uterus in dysmenorrhea rats so as to study its underlying analgesic mechanism. A total of 48 SD rats during diestrus were randomized into normal saline (control) group, model group and acupuncture group according to a random number table, with 16 rats in each group. Dysmenorrhea model was established by subcutaneous injection of Estradiol benzoate (0.5 mg/d on the 1st and 10th day, and 0.2 mg/d from day 2 to day 9, once daily for 10 days) and oxytocin (2 U/rat, once on day 10). Malondialdehyde (MDA) and beta-endorphin (beta-EP) contents in the uterus were detected by radioimmunoassay, and the heat shock protein 70 (HSP 70) immunoactivity of the uterus was detected by immunohistochemistry. In comparison with the control group, MDA content in the uterus was increased significantly in the model group (P < 0.01), while the beta-EP level and the immunoactivity of HSP 70 immune-reaction (IR) positive products in the uterus decrease significantly (P < 0.01) and moderately, respectively in the model group. In comparison with the model group, uterine MDA content in the EA group was decreased significantly (P < 0.01), while uterine beta-EP level increased considerably (P < 0.01) and HSP 70 expression was upregulated to a certain degree. EA of "Sanyinjiao" (SP 6) can reduce MDA content and upregulate beta-EP level of the uterus in rats with dysmenorrhea, which may contribute to its analgesic effect in relieving dysmenorrhea by clearing away oxygen free radicals and raising analgesic substance in the uterus.

Emergency department length of stay for ethanol intoxication encounters.

PubMed

Klein, Lauren R; Driver, Brian E; Miner, James R; Martel, Marc L; Cole, Jon B

2017-12-08

Emergency Department (ED) encounters for ethanol intoxication are becoming increasingly common. The purpose of this study was to explore factors associated with ED length of stay (LOS) for ethanol intoxication encounters. This was a multi-center, retrospective, observational study of patients presenting to the ED for ethanol intoxication. Data were abstracted from the electronic medical record. To explore factors associated with ED LOS, we created a mixed-effects generalized linear model. We identified 18,664 eligible patients from 6 different EDs during the study period (2012-2016). The median age was 37years, 69% were male, and the median ethanol concentration was 213mg/dL. Median LOS was 348min (range 43-1658). Using a mixed-effects generalized linear model, independent variables associated with a significant increase in ED LOS included use of parenteral sedation (beta=0.30, increase in LOS=34%), laboratory testing (beta=0.21, increase in LOS=23%), as well as the hour of arrival to the ED, such that patients arriving to the ED during evening hours (between 18:00 and midnight) had up to an 86% increase in LOS. Variables not significantly associated with an increase in LOS included age, gender, ethanol concentration, psychiatric disposition, using the ED frequently for ethanol intoxication, CT use, and daily ED volume. Variables such as diagnostic testing, treatments, and hour of arrival may influence ED LOS in patients with acute ethanol intoxication. Identification and further exploration of these factors may assist in developing hospital and community based improvements to modify LOS in this population. Copyright © 2017 Elsevier Inc. All rights reserved.

Formation, isomerization, and derivatization of Keggin tungstoaluminates.

PubMed

Cowan, J J; Bailey, A J; Heintz, R A; Do, B T; Hardcastle, K I; Hill, C L; Weinstock, I A

2001-12-17

Trends in the stability of alpha- and beta-Keggin heteropolytungstates of the second-row main-group heteroatoms Al(III), Si(IV), and P(V) are elaborated by data that establish the roles of kinetic and thermodynamic control in the formation and isomerization of Keggin tungstoaluminates. Slow, room-temperature co-condensation of Al(III) and W(VI) (2:11 molar ratio) in water gives a pH 7 solution containing beta(1) and beta(2) isomers of [Al(AlOH(2))W(11)O(39)](6)(-) (beta(1)- and beta(2)-1). Partial equilibration of this kinetic product mixture by gentle heating (2 h at 100 degrees C) or, alternatively, co-condensation of Al(III) and W(VI) for 2.5 h at 100 degrees C both give mixtures of beta(2)-, beta(3)-, and alpha-1. Full equilibration, by prolonged heating (25 days at 100 degrees C), gives an isomerically pure solution of alpha-1, thus demonstrating that isomerization occurs in the direction beta(1) --> beta(2) --> beta(3) --> alpha. Furthermore, kinetically controlled conversions of 1 to H(5)[AlW(12)O(40)] (2)-achieved by heating pH 0-0.2 solutions of 1 for 5 days at 100 degrees C-occur with retention of isomeric integrity, such that alpha-1 is converted to alpha-2 (92%; 8% beta), while mixtures of beta(2)- and beta(3)-1 are converted to beta-2 (87%; 13% alpha). These data, when combined with previously reported observations (equilibria between alpha- and beta-2, kinetically controlled hydrolyses of alpha-2 to alpha-[AlW(11)O(39)](9)(-) (alpha-3) and of beta-2 to beta(2)-3, and equilibria between beta(3)- and alpha-3), provide a comprehensive picture regarding the roles of kinetic and thermodynamic control. Finally, a general method for preparation of the isomerically pure derivatives alpha-K(9)(-)(n)()[AlM(n)()(+)W(11)O(39)] (4), M(n)()(+) = Al(III), [V(IV)O](2+), [V(V)O](3+), Mn(II), Mn(III), Mn(IV), Co(II), and Co(III), is provided. The presence of Mn(IV) is confirmed by cyclic voltammetry, pK(a) values of the aquo ligands on 4 are determined by pH titration, and the isomeric structure of these derivatives is established by (27)Al, (51)V, and (183)W NMR and IR spectroscopies and X-ray crystallography.

Populational Growth Models Proportional to Beta Densities with Allee Effect

NASA Astrophysics Data System (ADS)

Aleixo, Sandra M.; Rocha, J. Leonel; Pestana, Dinis D.

2009-05-01

We consider populations growth models with Allee effect, proportional to beta densities with shape parameters p and 2, where the dynamical complexity is related with the Malthusian parameter r. For p>2, these models exhibit a population dynamics with natural Allee effect. However, in the case of 1

Modulation of TGF-beta signaling during progression of chronic liver diseases.

PubMed

Matsuzaki, Koichi

2009-01-01

A large body of work has established roles for epithelial cells as important mediators of progressive fibrosis and carcinogenesis. Transforming growth factor-beta (TGF-beta) and pro-inflammatory cytokines are important inducers of fibro-carcinogenesis. TGF-beta signaling involves phosphorylation of Smad3 at middle linker and/or C-terminal regions. Reversible shifting of Smad3-dependent signaling between tumor-suppression and oncogenesis in hyperactive Ras-expressing epithelial cells indicates that Smad3 phosphorylated at the C-terminal region (pSmad3C) transmits a tumor-suppressive TGF-beta signal, while oncogenic activities such as cell proliferation and invasion are promoted by Smad3 phosphorylated at the linker region (pSmad3L). Notably, pSmad3L-mediated signaling promotes extracellular matrix deposition by activated mesenchymal cells. During progression of chronic liver diseases, hepatic epithelial hepatocytes undergo transition from the tumor-suppressive pSmad3C pathway to the fibrogenic/oncogenic pSmad3L pathway, accelerating liver fibrosis and increasing risk of hepatocellular carcinoma. c-Jun N-terminal kinase activated by pro-inflammatory cytokines is mediating this perturbed hepatocytic TGF-beta signaling. Thus, TGF-beta signaling of hepatocytes affected by chronic inflammation offers a general framework for understanding the molecular mechanisms of human fibro-carcinogenesis during progression of chronic liver diseases.

Enzymes in Commercial Cellulase Preparations Bind Differently to Dioxane Extracted Lignins

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yarbrough, John M.; Mittal, Ashutosh; Katahira, Rui

Commercial fungal cellulases used in biomass-to-biofuels processes can be grouped into three general classes: native, augmented, and engineered. To evaluate lignin binding affinities of different enzyme activities in various commercial cellulase formulations in order to determine if enzyme losses due to lignin binding can be modulated by using different enzymes of the same activity We used water:dioxane (1:9) to extract lignin from pretreated corn stover. Commercial cellulases were incubated with lignin and the unbound supernatants were evaluated for individual enzyme loss by SDS=PAGE and these were correlated with activity loss using various pNP-sugar substrates. Colorimetric assays for general glycosyl hydrolasemore » activities showed distinct differences in enzyme binding to lignin for each enzyme activity. Native systems demonstrated low binding of endo- and exo-cellulases, high binding of xylanase, and moderate ..beta..-glucosidase binding. Engineered cellulase mixtures exhibited low binding of exo-cellulases, very strong binding of endocellulases and ..beta..- glucosidase, and mixed binding of xylanase activity. The augmented cellulase had low binding of exocellulase, high binding of endocellulase and xylanase, and moderate binding of ..beta..-glucosidase activities. Bound and unbound activities were correlated with general molecular weight ranges of proteins as measured by loss of proteins bands in bound fractions on SDS-PAGE gels. Lignin-bound high molecular weight bands correlated with binding of ..beta..-glucosidase activity. While ..beta..-glucosidases demonstrated high binding in many cases, they have been shown to remain active. Bound low molecular weight bands correlated with xylanase activity binding. Contrary to other literature, exocellulase activity did not show strong lignin binding. The variation in enzyme activity binding between the three classes of cellulases preparations indicate that it is certainly possible to alter the binding of specific glycosyl hydrolase activities. It remains unclear whether loss of endocellulase activity to lignin binding is problematic for biomass conversion.« less

Dissecting the role of matrix metalloproteinases (MMP) and integrin alpha(v)beta3 in angiogenesis in vitro: absence of hemopexin C domain bioactivity, but membrane-Type 1-MMP and alpha(v)beta3 are critical.

PubMed

Nisato, Riccardo E; Hosseini, Ghamartaj; Sirrenberg, Christian; Butler, Georgina S; Crabbe, Thomas; Docherty, Andrew J P; Wiesner, Matthias; Murphy, Gillian; Overall, Christopher M; Goodman, Simon L; Pepper, Michael S

2005-10-15

Matrix metalloproteinase (MMP)-2 and its hemopexin C domain autolytic fragment (also called PEX) have been proposed to be crucial for angiogenesis. Here, we have investigated the dependency of in vitro angiogenesis on MMP-mediated extracellular proteolysis and integrin alpha(v)beta3-mediated cell adhesion in a three-dimensional collagen I model. The hydroxamate-based synthetic inhibitors BB94, CT1399, and CT1847 inhibited endothelial cell invasion, as did neutralizing anti-membrane-type 1-MMP (MT1-MMP) antibodies and tissue inhibitor of MMP (TIMP)-2 and TIMP-3 but not TIMP-1. This confirmed the pivotal importance of MT1-MMP over other MMPs in this model. Invasion was also inhibited by a nonpeptidic antagonist of integrin alpha(v)beta3, EMD 361276. Although PEX strongly inhibited pro-MMP-2 activation, when contaminating lipopolysaccharide was neutralized, PEX neither affected angiogenesis nor bound integrin alpha(v)beta(3). Moreover, no specific binding of pro-MMP-2 to integrin alpha(v)beta3 was found, whereas only one out of four independently prepared enzymatically active MMP-2 preparations could bind integrin alpha(v)beta3 , and this in a PEX-independent manner. Likewise, integrin alpha(v)beta3 -expressing cells did not bind MMP-2-coated surfaces. Hence, these findings show that endothelial cell invasion of collagen I gels is MT1-MMP and alpha(v)beta3 - dependent but MMP-2 independent and does not support a role for PEX in alpha(v)beta3 integrin binding or in modulating angiogenesis in this system.

Coping styles in heart failure patients with depressive symptoms.

PubMed

Trivedi, Ranak B; Blumenthal, James A; O'Connor, Christopher; Adams, Kirkwood; Hinderliter, Alan; Dupree, Carla; Johnson, Kristy; Sherwood, Andrew

2009-10-01

Elevated depressive symptoms have been linked to poorer prognosis in heart failure (HF) patients. Our objective was to identify coping styles associated with depressive symptoms in HF patients. A total of 222 stable HF patients (32.75% female, 45.4% non-Hispanic black) completed multiple questionnaires. Beck Depression Inventory (BDI) assessed depressive symptoms, Life Orientation Test (LOT-R) assessed optimism, ENRICHD Social Support Inventory (ESSI) and Perceived Social Support Scale (PSSS) assessed social support, and COPE assessed coping styles. Linear regression analyses were employed to assess the association of coping styles with continuous BDI scores. Logistic regression analyses were performed using BDI scores dichotomized into BDI<10 vs. BDI> or =10, to identify coping styles accompanying clinically significant depressive symptoms. In linear regression models, higher BDI scores were associated with lower scores on the acceptance (beta=-.14), humor (beta=-.15), planning (beta=-.15), and emotional support (beta=-.14) subscales of the COPE, and higher scores on the behavioral disengagement (beta=.41), denial (beta=.33), venting (beta=.25), and mental disengagement (beta=.22) subscales. Higher PSSS and ESSI scores were associated with lower BDI scores (beta=-.32 and -.25, respectively). Higher LOT-R scores were associated with higher BDI scores (beta=.39, P<.001). In logistical regression models, BDI> or =10 was associated with greater likelihood of behavioral disengagement (OR=1.3), denial (OR=1.2), mental disengagement (OR=1.3), venting (OR=1.2), and pessimism (OR=1.2), and lower perceived social support measured by PSSS (OR=.92) and ESSI (OR=.92). Depressive symptoms in HF patients are associated with avoidant coping, lower perceived social support, and pessimism. Results raise the possibility that interventions designed to improve coping may reduce depressive symptoms.

Varietal differences in the bioaccessibility of beta-carotene from mango (Mangifera indica) and papaya (Carica papaya) fruits.

PubMed

Veda, Supriya; Platel, Kalpana; Srinivasan, K

2007-09-19

Mango and papaya, which are rich sources of beta-carotene, are widely consumed in India. In this study, beta-carotene content and its bioaccessibility were determined in six locally available varieties of mango, namely, Badami, Raspuri, Mallika, Malgoa, Totapuri, and Neelam, and two varieties of papaya, namely, Honey Dew and Surya. Varietal differences were evident in both beta-carotene content and its bioaccessibility in the case of mango. beta-Carotene content in ripe mango ranged from 0.55 +/- 0.03 mg/100 g in the Malgoa variety to 3.21 +/- 0.25 mg/100 g in the Badami variety. Similarly, in the Honey Dew and Surya varieties of papaya, beta-carotene contents were 0.70 +/- 0.10 and 0.74 +/- 0.12 mg/100 g, respectively. Bioaccessibility of beta-carotene ranged from 24.5% in Badami to 39.1% in Raspuri varieties of mango. Considering both the percent bioaccessibility and the inherent beta-carotene content, the amount of bioaccessible beta-carotene was highest in the Mallika variety (0.89 mg/100 g), followed by Badami (0.79 mg/100 g). Because mango and papaya are also consumed as a blend with milk, the influence of the presence of milk on the bioaccessibility of beta-carotene from these fruits was also examined. Addition of milk generally brought about a significant increase in the bioaccessibility of beta-carotene from mango, the increase ranging from 12 to 56%. Bioaccessibility of beta-carotene from the two varieties of papaya examined was similar (31.4-34.3%). Addition of milk increased this bioaccessibility by 19 and 38% in these two varieties. Considering the beta-carotene content of mango and papaya, the latter has to be consumed in amounts roughly 3 times that of mango to derive the same amount of beta-carotene. Thus, this study has indicated that varietal differences exist in the content and bioaccessibility of beta-carotene in mango and that the addition of milk is advantageous in deriving this provitamin A from the fruit pulp of mango and papaya.

Developing injectable immunoglobulins to treat cognitive impairment in Alzheimer's disease.

PubMed

Steinitz, Michael

2008-05-01

Alzheimer's disease is a devastating disorder, clinically characterized by a comprehensive cognitive decline. The novel strategy of anti-amyloid-beta immunotherapy has been suggested following encouraging results obtained in murine models of Alzheimer's disease, in non-human primates, and in small-scale clinical trials. To examine the choice between active or passive anti-amyloid-beta immunization and the choice of the molecule to which the immune machinery should be targeted, which are central issues in future immune therapy of Alzheimer's disease. Research into the new area of Alzheimer's disease immune therapy is primarily based on in vivo and in vitro studies of murine models of Alzheimer's disease. The studies are hence limited to defined genetic deficiencies. In humans, infusion of anti-amyloid-beta antibodies is considered a safer approach than active anti-amyloid-beta vaccination. Alzheimer's-disease-protective anti-amyloid-beta monoclonal antibodies should target specific epitopes within the amyloid beta(1 42) peptide, avoiding possibly harmful binding to the ubiquitous normal amyloid precursor protein. Since Alzheimer's disease immunotherapy requires repeated infusion of antibodies over a prolonged period of time, Alzheimer's disease patients will tolerate such antibodies provided the latter are exclusively of human origin. Human monoclonal antibodies that correspond to ubiquitous anti-amyloid-beta, present in all healthy humans, might bear important protective characteristics.

Study of nuclear structure of 76-86Sr isotopes in the pn interacting boson model

NASA Astrophysics Data System (ADS)

Saxena, M.; Gupta, J. B.; Mandal, S.

2015-08-01

The proton neutron interacting boson model (IBM-2) has been used to make a systematic study of Strontium isotopes in this mass region of A ˜ 80 with 38 ≤slant N ≤slant 48 and Z = 38. The three-term Talmi-Otsuka general Hamiltonian in the framework of the neutron proton version of the Interaction boson model was used to perform the calculations. The yrast levels energy are reproduced. The beta and gamma band energy levels also matched well. The reduced transition probabilities were also calculated and were found to be in agreement with the experimental values. In addition, g-factor for the {2}1+ state was evaluated. Possible candidates for mixed symmetry states were also predicted for several nuclei in this isotopic chain.

Treatment of generalized anxiety disorder: comparison of a new beta-blocking drug (CGP 361 A), low-dose neuroleptic (flupenthixol), and placebo.

PubMed

Bjerrum, H; Allerup, P; Thunedborg, K; Jakobsen, K; Bech, P

1992-09-01

In an attempt to evaluate an alternative drug treatment to benzodiazepines in generalized anxiety disorders, a placebo controlled trial was carried out with a new beta-adrenergic blocker (CPG 361 A). A low-dosage neuroleptic (flupenthixol) was included as a reference drug. Depending on the clinical assessment scales the placebo treatment resulted in moderate to excellent improvement in 36% to 56% of the patients after four weeks of treatment. The active drugs generally had a higher improvement range (from 31% to 80%). The global improvement scale was found to be better than the other scales in discriminating between placebo (50% improvement) and the active drugs (CGP 361 A brought about 78% improvement and flupenthixol brought about 80% improvement). However, only for flupenthixol was the difference of statistical significance.

Immortal time bias in pharmacoepidemiological studies on cancer patient survival: empirical illustration for beta-blocker use in four cancers with different prognosis.

PubMed

Weberpals, Janick; Jansen, Lina; van Herk-Sukel, Myrthe P P; Kuiper, Josephina G; Aarts, Mieke J; Vissers, Pauline A J; Brenner, Hermann

2017-11-01

Immortal time bias (ITB) is still seen frequently in medical literature. However, not much is known about this bias in the field of cancer (pharmaco-)epidemiology. In context of a hypothetical beneficial beta-blocker use among cancer patients, we aimed to demonstrate the magnitude of ITB among 9876 prostate, colorectal, lung and pancreatic cancer patients diagnosed between 1998 and 2011, which were selected from a database linkage of the Netherlands Cancer Registry and the PHARMO Database Network. Hazard ratios (HR) and 95% confidence intervals from three ITB scenarios, defining exposure at a defined point after diagnosis (model 1), at any point after diagnosis (model 2) and as multiple exposures after diagnosis (model 3), were calculated to investigate the association between beta-blockers and cancer prognosis using Cox proportional hazards regression. Results were compared to unbiased estimates derived from the Mantel-Byar model. Ignoring ITB led to substantial smaller HRs for beta-blocker use proposing a significant protective association in all cancer types [e.g. HR 0.18 (0.07-0.43) for pancreatic cancer in model 1], whereas estimates derived from the Mantel-Byar model were mainly suggesting no association [e.g. HR 1.10 (0.84-1.44)]. The magnitude of bias was consistently larger among cancer types with worse prognosis [overall median HR differences between all scenarios in model 1 and Mantel-Byar model of 0.56 (prostate), 0.72 (colorectal), 0.77 (lung) and 0.85 (pancreas)]. In conclusion, ITB led to spurious beneficial associations of beta-blocker use among cancer patients. The magnitude of ITB depends on the duration of excluded immortal time and the prognosis of each cancer.

Stabilization of model beverage cloud emulsions using protein-polysaccharide electrostatic complexes formed at the oil-water interface.

PubMed

Harnsilawat, Thepkunya; Pongsawatmanit, Rungnaphar; McClements, David J

2006-07-26

The potential of utilizing interfacial complexes, formed through the electrostatic interactions of proteins and polysaccharides at oil-water interfaces, to stabilize model beverage cloud emulsions has been examined. These interfacial complexes were formed by mixing charged polysaccharides with oil-in-water emulsions containing oppositely charged protein-coated oil droplets. Model beverage emulsions were prepared that consisted of 0.1 wt % corn oil droplets coated by beta-lactoglobulin (beta-Lg), beta-Lg/alginate, beta-Lg/iota-carrageenan, or beta-Lg/gum arabic interfacial layers (pH 3 or 4). Stable emulsions were formed when the polysaccharide concentration was sufficient to saturate the protein-coated droplets. The emulsions were subjected to variations in pH (from 3 to 7), ionic strength (from 0 to 250 mM NaCl), and thermal processing (from 30 or 90 degrees C), and the influence on their stability was determined. The emulsions containing alginate and carrageenan had the best stability to ionic strength and thermal processing. This study shows that the controlled formation of protein-polysaccharide complexes at droplet surfaces may be used to produce stable beverage emulsions, which may have important implications for industrial applications.

Statistical downscaling of precipitation using long short-term memory recurrent neural networks

NASA Astrophysics Data System (ADS)

Misra, Saptarshi; Sarkar, Sudeshna; Mitra, Pabitra

2017-11-01

Hydrological impacts of global climate change on regional scale are generally assessed by downscaling large-scale climatic variables, simulated by General Circulation Models (GCMs), to regional, small-scale hydrometeorological variables like precipitation, temperature, etc. In this study, we propose a new statistical downscaling model based on Recurrent Neural Network with Long Short-Term Memory which captures the spatio-temporal dependencies in local rainfall. The previous studies have used several other methods such as linear regression, quantile regression, kernel regression, beta regression, and artificial neural networks. Deep neural networks and recurrent neural networks have been shown to be highly promising in modeling complex and highly non-linear relationships between input and output variables in different domains and hence we investigated their performance in the task of statistical downscaling. We have tested this model on two datasets—one on precipitation in Mahanadi basin in India and the second on precipitation in Campbell River basin in Canada. Our autoencoder coupled long short-term memory recurrent neural network model performs the best compared to other existing methods on both the datasets with respect to temporal cross-correlation, mean squared error, and capturing the extremes.

Prenatal programming of metabolic syndrome in the common marmoset is associated with increased expression of 11beta-hydroxysteroid dehydrogenase type 1.

PubMed

Nyirenda, Moffat J; Carter, Roderick; Tang, Justin I; de Vries, Annick; Schlumbohm, Christina; Hillier, Stephen G; Streit, Frank; Oellerich, Michael; Armstrong, Victor W; Fuchs, Eberhard; Seckl, Jonathan R

2009-12-01

Recent studies in humans and animal models of obesity have shown increased adipose tissue activity of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1), which amplifies local tissue glucocorticoid concentrations. The reasons for this 11beta-HSD1 dysregulation are unknown. Here, we tested whether 11beta-HSD1 expression, like the metabolic syndrome, is "programmed" by prenatal environmental events in a nonhuman primate model, the common marmoset monkey. We used a "fetal programming" paradigm where brief antenatal exposure to glucocorticoids leads to the metabolic syndrome in the offspring. Pregnant marmosets were given the synthetic glucocorticoid dexamethasone orally for 1 week in either early or late gestation, or they were given vehicle. Tissue 11beta-HSD1 and glucocorticoid receptor mRNA expression were examined in the offspring at 4 and 24 months of age. Prenatal dexamethasone administration, selectively during late gestation, resulted in early and persistent elevations in 11beta-HSD1 mRNA expression and activity in the liver, pancreas, and subcutaneous-but not visceral-fat. The increase in 11beta-HSD1 occurred before animals developed obesity or overt features of the metabolic syndrome. In contrast to rodents, in utero dexamethasone exposure did not alter glucocorticoid receptor expression in metabolic tissues in marmosets. These data suggest that long-term upregulation of 11beta-HSD1 in metabolically active tissues may follow prenatal "stress" hormone exposure and indicates a novel mechanism for fetal origins of adult obesity and the metabolic syndrome.

Changes in beta-actin mRNA expression in remodeling canine myocardium.

PubMed

Carlyle, W C; Toher, C A; Vandervelde, J R; McDonald, K M; Homans, D C; Cohn, J N

1996-01-01

Beta-actin, a cytoskeletal protein important in the maintenance of cytoarchitecture, has long been thought to be expressed constitutively in myocardial tissue. As such, beta-actin mRNA has been used as a control gene in a wide range of experiments. However, we have uncovered consistent changes in beta-actin mRNA expression in canine myocardium remodeling as a result of insult to the left ventricle. The experimental canine models used were either DC shock damage to the left ventricle or volume overload resulting from severe mitral regurgitation. The remodeling process in both canine models is characterized by an increase in left ventricular mass. PCR amplification using primers designed to selectively amplify the 3' end and a portion of the 3' untranslated region of beta-actin mRNA resulted in the generation of a 297 base pair product predominant only in normal canine myocardium and a 472 base pair product that became increasingly prominent from 1 to 30 days after DC shock damage to the left ventricle and from 10 to 90 days after creation of mitral regurgitation. Northern analysis showed a three-fold increase in beta-actin mRNA after either DC shock or creation of mitral regurgitation. Western analysis revealed an early increase in beta-actin protein followed by an apparent decrease to below baseline levels. These observations suggest that changes in beta-actin mRNA expression accompany the structural alterations that occur in response to myocardial damage. Whether or not the changes in beta-actin mRNA expression play a role in mediating these structural alterations remains to be determined.

Unraveling the contribution of pancreatic beta-cell suicide in autoimmune type 1 diabetes✩

PubMed Central

Jaberi-Douraki, Majid; Schnell, Santiago; Pietropaolo, Massimo; Khadra, Anmar

2014-01-01

In type 1 diabetes, an autoimmune disease mediated by autoreactive T-cells that attack insulin-secreting pancreatic beta-cells, it has been suggested that disease progression may additionally require protective mechanisms in the target tissue to impede such auto-destructive mechanisms. We hypothesize that the autoimmune attack against beta-cells causes endoplasmic reticulum stress by forcing the remaining beta-cells to synthesize and secrete defective insulin. To rescue beta-cell from the endoplasmic reticulum stress, beta-cells activate the unfolded protein response to restore protein homeostasis and normal insulin synthesis. Here we investigate the compensatory role of unfolded protein response by developing a multi-state model of type 1 diabetes that takes into account beta-cell destruction caused by pathogenic autoreactive T-cells and apoptosis triggered by endoplasmic reticulum stress. We discuss the mechanism of unfolded protein response activation and how it counters beta-cell extinction caused by an autoimmune attack and/or irreversible damage by endoplasmic reticulum stress. Our results reveal important insights about the balance between beta-cell destruction by autoimmune attack (beta-cell homicide) and beta-cell apoptosis by endoplasmic reticulum stress (beta-cell suicide). It also provides an explanation as to why the unfolded protein response may not be a successful therapeutic target to treat type 1 diabetes. PMID:24831415

A Better Lemon Squeezer? Maximum-Likelihood Regression with Beta-Distributed Dependent Variables

ERIC Educational Resources Information Center

Smithson, Michael; Verkuilen, Jay

2006-01-01

Uncorrectable skew and heteroscedasticity are among the "lemons" of psychological data, yet many important variables naturally exhibit these properties. For scales with a lower and upper bound, a suitable candidate for models is the beta distribution, which is very flexible and models skew quite well. The authors present…

Caliber Schools. Caliber: Beta Academy

ERIC Educational Resources Information Center

EDUCAUSE, 2015

2015-01-01

Caliber: Beta Academy is reimagining education as we know it, with the belief that the innovations in its model will allow 100% of its students to graduate ready to attend and succeed in a competitive four-year college and beyond. The academic model of the school features personalized learning plans, blended learning for English and math,…

Selective extinction drives taxonomic and functional alpha and beta diversities in island bird assemblages.

PubMed

Si, Xingfeng; Baselga, Andrés; Leprieur, Fabien; Song, Xiao; Ding, Ping

2016-03-01

Taxonomic diversity considers all species being equally different from each other and thus disregards species' different ecological functions. Exploring taxonomic and functional aspects of biodiversity simultaneously can better understand the processes of community assembly. We analysed taxonomic and functional alpha and beta diversities of breeding bird assemblages on land-bridge islands in the Thousand Island Lake, China. Given the high dispersal ability of most birds at this spatial scale (several kilometres), we predicted (i) selective extinction driving alpha and beta diversities after the creation of land-bridge islands of varying area and (ii) low taxonomic and functional beta diversities that were not correlated to spatial distance. Breeding birds were surveyed on 37 islands annually from 2007 to 2014. We decomposed beta diversity of breeding birds into spatial turnover and nestedness-resultant components, and related taxonomic and functional diversities to island area and isolation using power regression models (for alpha diversity) and multiple regression models on distance matrices (for beta diversity). We then ran simulations to assess the strength of the correlations between taxonomic and functional diversities. Results revealed that both taxonomic and functional alpha diversities increased with island area. The taxonomic nestedness-resultant and turnover components increased and decreased with difference in area, respectively, but functional counterparts did not. Isolation played a minor role in explaining alpha- and beta-diversity patterns. By partitioning beta diversity, we found low levels of overall taxonomic and functional beta diversities. The functional nestedness-resultant component dominated overall functional beta diversity, whereas taxonomic turnover was the dominant component for taxonomic beta diversity. The simulation showed that functional alpha and beta diversities were significantly correlated with taxonomic diversities, and the observed values of correlations were significantly different from null expectations of random extinction. Our assessment of island bird assemblages validated the predictions of no distance effects and low beta diversity due to pervasive dispersal events among islands and also suggested that selective extinction drives taxonomic and functional alpha and beta diversities. The contrasting turnover and nestedness-resultant components of taxonomic and functional beta diversities demonstrate the importance of considering the multifaceted nature of biodiversity when examining community assembly. © 2015 The Authors. Journal of Animal Ecology © 2015 British Ecological Society.

Beta-decay spectroscopy relevant to the r-process nucleosynthesis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nishimura, Shunji; Collaboration: RIBF Decay Collaboration

2012-11-12

A scientific program of beta-decay spectroscopy relevant to r-process nucleosynthesis has been started using high intensity U-beam at the RIBF. The first results of {beta}-decay half-lives of very neutron-rich Kr to Tc nuclides, all of which lie close to the r-process path, suggest a systematic enhancement of the the {beta}-decay rates of the Zr and Nb isotopes around A110 with respect to the predictions of the deformed quasiparticle-random-phase-approximation model (FRDM + QRPA). An impact of the results on the astrophysical r-process is discussed together with the future perspective of the {beta}-decay spectroscopy with the EURICA.

Status of double beta decay experiments using isotopes other than 136Xe

NASA Astrophysics Data System (ADS)

Pandola, L.

2014-09-01

Neutrinoless double beta decay is a lepton-number violating process predicted by many extensions of the standard model. It is actively searched for in several candidate isotopes within many experimental projects. The status of the experimental initiatives which are looking for the neutrinoless double beta decay in isotopes other than 136Xe is reviewed, with special emphasis given to the projects that passed the R&D phase. The results recently released by the experiment GERDA are also summarized and discussed. The GERDA data give no positive indication of neutrinoless double beta decay of 76Ge and disfavor in a model-independent way the long-standing observation claim on the same isotope. The lower limit reported by GERDA for the half-life of neutrinoless double beta decay of 76Ge is T1/20ν > 2.1 ṡ1025 yr (90% C.L.), or T1/20ν > 3.0 ṡ1025 yr, when combined with the results of other 76Ge predecessor experiments.

Monte Carlo calculation of the sensitivity of a commercial dose calibrator to gamma and beta radiation.

PubMed

Laedermann, Jean-Pascal; Valley, Jean-François; Bulling, Shelley; Bochud, François O

2004-06-01

The detection process used in a commercial dose calibrator was modeled using the GEANT 3 Monte Carlo code. Dose calibrator efficiency for gamma and beta emitters, and the response to monoenergetic photons and electrons was calculated. The model shows that beta emitters below 2.5 MeV deposit energy indirectly in the detector through bremsstrahlung produced in the chamber wall or in the source itself. Higher energy beta emitters (E > 2.5 MeV) deposit energy directly in the chamber sensitive volume, and dose calibrator sensitivity increases abruptly for these radionuclides. The Monte Carlo calculations were compared with gamma and beta emitter measurements. The calculations show that the variation in dose calibrator efficiency with measuring conditions (source volume, container diameter, container wall thickness and material, position of the source within the calibrator) is relatively small and can be considered insignificant for routine measurement applications. However, dose calibrator efficiency depends strongly on the inner-wall thickness of the detector.

Glassy aging with modified Kohlrausch-Williams-Watts form

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sen Gupta, Bhaskar; Das, Shankar P.

2007-12-15

In this paper, we address the question of whether aging in the nonequilibrium glassy state is controlled by the equilibrium {alpha}-relaxation process, which occurs at temperatures above T{sub g}. Recently, Lunkenheimer et al. [Phys. Rev. Lett. 95, 055702 (2005)] proposed a model for the glassy aging data of dielectric relaxation using a modified Kohlrausch-Williams-Watts form exp[-(t{sub age}/{tau}{sub age}){sup {beta}{sub age}}]. The aging time t{sub age} dependence of the relaxation time {tau}{sub age} is defined by these authors through a functional relation involving the corresponding frequency {nu}(t{sub age})=1/(2{pi}{tau}{sub age}), but the stretching exponent {beta}{sub age} is the same as {beta}{sub {alpha}},more » the {alpha}-relaxation stretching exponent. We present here an alternative functional form for {tau}{sub age}(t{sub age}) directly involving the relaxation time itself. The proposed model fits the data of Lunkenheimer et al. perfectly with a stretching exponent {beta}{sub age} different from {beta}{sub {alpha}}.« less

Top-Down Beta Rhythms Support Selective Attention via Interlaminar Interaction: A Model

PubMed Central

Lee, Jung H.; Whittington, Miles A.; Kopell, Nancy J.

2013-01-01

Cortical rhythms have been thought to play crucial roles in our cognitive abilities. Rhythmic activity in the beta frequency band, around 20 Hz, has been reported in recent studies that focused on neural correlates of attention, indicating that top-down beta rhythms, generated in higher cognitive areas and delivered to earlier sensory areas, can support attentional gain modulation. To elucidate functional roles of beta rhythms and underlying mechanisms, we built a computational model of sensory cortical areas. Our simulation results show that top-down beta rhythms can activate ascending synaptic projections from L5 to L4 and L2/3, responsible for biased competition in superficial layers. In the simulation, slow-inhibitory interneurons are shown to resonate to the 20 Hz input and modulate the activity in superficial layers in an attention-related manner. The predicted critical roles of these cells in attentional gain provide a potential mechanism by which cholinergic drive can support selective attention. PMID:23950699

Predictive modelling of JT-60SA high-beta steady-state plasma with impurity accumulation

NASA Astrophysics Data System (ADS)

Hayashi, N.; Hoshino, K.; Honda, M.; Ide, S.

2018-06-01

The integrated modelling code TOPICS has been extended to include core impurity transport, and applied to predictive modelling of JT-60SA high-beta steady-state plasma with the accumulation of impurity seeded to reduce the divertor heat load. In the modelling, models and conditions are selected for a conservative prediction, which considers a lower bound of plasma performance with the maximum accumulation of impurity. The conservative prediction shows the compatibility of impurity seeding with core plasma with high-beta (β N  >  3.5) and full current drive conditions, i.e. when Ar seeding reduces the divertor heat load below 10 MW m‑2, its accumulation in the core is so moderate that the core plasma performance can be recovered by additional heating within the machine capability to compensate for Ar radiation. Due to the strong dependence of accumulation on the pedestal density gradient, high separatrix density is important for the low accumulation as well as the low divertor heat load. The conservative prediction also shows that JT-60SA has enough capability to explore the divertor heat load control by impurity seeding in high-beta steady-state plasmas.

A robust direct-integration method for rotorcraft maneuver and periodic response

NASA Technical Reports Server (NTRS)

Panda, Brahmananda

1992-01-01

The Newmark-Beta method and the Newton-Raphson iteration scheme are combined to develop a direct-integration method for evaluating the maneuver and periodic-response expressions for rotorcraft. The method requires the generation of Jacobians and includes higher derivatives in the formulation of the geometric stiffness matrix to enhance the convergence of the system. The method leads to effective convergence with nonlinear structural dynamics and aerodynamic terms. Singularities in the matrices can be addressed with the method as they arise from a Lagrange multiplier approach for coupling equations with nonlinear constraints. The method is also shown to be general enough to handle singularities from quasisteady control-system models. The method is shown to be more general and robust than the similar 2GCHAS method for analyzing rotorcraft dynamics.

Surgical Injury to the Mouse Pancreas through Ligation of the Pancreatic Duct as a Model for Endocrine and Exocrine Reprogramming and Proliferation

PubMed Central

De Groef, Sofie; Leuckx, Gunter; Van Gassen, Naomi; Staels, Willem; Cai, Ying; Yuchi, Yixing; Coppens, Violette; De Leu, Nico; Heremans, Yves; Baeyens, Luc; Van de Casteele, Mark; Heimberg, Harry

2015-01-01

Expansion of pancreatic beta cells in vivo or ex vivo, or generation of beta cells by differentiation from an embryonic or adult stem cell, can provide new expandable sources of beta cells to alleviate the donor scarcity in human islet transplantation as therapy for diabetes. Although recent advances have been made towards this aim, mechanisms that regulate beta cell expansion and differentiation from a stem/progenitor cell remain to be characterized. Here, we describe a protocol for an injury model in the adult mouse pancreas that can function as a tool to study mechanisms of tissue remodeling and beta cell proliferation and differentiation. Partial duct ligation (PDL) is an experimentally induced injury of the rodent pancreas involving surgical ligation of the main pancreatic duct resulting in an obstruction of drainage of exocrine products out of the tail region of the pancreas. The inflicted damage induces acinar atrophy, immune cell infiltration and severe tissue remodeling. We have previously reported the activation of Neurogenin (Ngn) 3 expressing endogenous progenitor-like cells and an increase in beta cell proliferation after PDL. Therefore, PDL provides a basis to study signals involved in beta cell dynamics and the properties of an endocrine progenitor in adult pancreas. Since, it still remains largely unclear, which factors and pathways contribute to beta cell neogenesis and proliferation in PDL, a standardized protocol for PDL will allow for comparison across laboratories. PMID:26273954

Phosphate and HEPES buffers potently affect the fibrillation and oligomerization mechanism of Alzheimer's A{beta} peptide

DOE Office of Scientific and Technical Information (OSTI.GOV)

Garvey, Megan; Tepper, Katharina; Haupt, Caroline

Highlights: {yields} Sodium phosphate buffer accelerated A{beta}(1-40) nucleation relative to HEPES. {yields} A{beta}(1-40) fibrils formed in the two buffers show only minor structural differences. {yields} NMR revealed that A{beta}(1-40) histidine residues mediate buffer dependent changes. -- Abstract: The oligomerization of A{beta} peptide into amyloid fibrils is a hallmark of Alzheimer's disease. Due to its biological relevance, phosphate is the most commonly used buffer system for studying the formation of A{beta} and other amyloid fibrils. Investigation into the characteristics and formation of amyloid fibrils frequently relies upon material formed in vitro, predominantly in phosphate buffers. Herein, we examine the effects onmore » the fibrillation and oligomerization mechanism of A{beta} peptide that occur due solely to the influence of phosphate buffer. We reveal that significant differences in amyloid fibrillation are observed due to fibrillation being initiated in phosphate or HEPES buffer (at physiological pH and temperature). Except for the differing buffer ions, all experimental parameters were kept constant. Fibril formation was assessed using fluorescently monitored kinetic studies, microscopy, X-ray fiber diffraction and infrared and nuclear magnetic resonance spectroscopies. Based on this set up, we herein reveal profound effects on the mechanism and speed of A{beta} fibrillation. The three histidine residues at positions 6, 13 and 14 of A{beta}(1-40) are instrumental in these mechanistic changes. We conclude that buffer plays a more significant role in fibril formation than has been generally acknowledged.« less

Modeling beta-adrenergic control of cardiac myocyte contractility in silico.

PubMed

Saucerman, Jeffrey J; Brunton, Laurence L; Michailova, Anushka P; McCulloch, Andrew D

2003-11-28

The beta-adrenergic signaling pathway regulates cardiac myocyte contractility through a combination of feedforward and feedback mechanisms. We used systems analysis to investigate how the components and topology of this signaling network permit neurohormonal control of excitation-contraction coupling in the rat ventricular myocyte. A kinetic model integrating beta-adrenergic signaling with excitation-contraction coupling was formulated, and each subsystem was validated with independent biochemical and physiological measurements. Model analysis was used to investigate quantitatively the effects of specific molecular perturbations. 3-Fold overexpression of adenylyl cyclase in the model allowed an 85% higher rate of cyclic AMP synthesis than an equivalent overexpression of beta 1-adrenergic receptor, and manipulating the affinity of Gs alpha for adenylyl cyclase was a more potent regulator of cyclic AMP production. The model predicted that less than 40% of adenylyl cyclase molecules may be stimulated under maximal receptor activation, and an experimental protocol is suggested for validating this prediction. The model also predicted that the endogenous heat-stable protein kinase inhibitor may enhance basal cyclic AMP buffering by 68% and increasing the apparent Hill coefficient of protein kinase A activation from 1.0 to 2.0. Finally, phosphorylation of the L-type calcium channel and phospholamban were found sufficient to predict the dominant changes in myocyte contractility, including a 2.6x increase in systolic calcium (inotropy) and a 28% decrease in calcium half-relaxation time (lusitropy). By performing systems analysis, the consequences of molecular perturbations in the beta-adrenergic signaling network may be understood within the context of integrative cellular physiology.

Modeling beta-adrenergic control of cardiac myocyte contractility in silico

NASA Technical Reports Server (NTRS)

Saucerman, Jeffrey J.; Brunton, Laurence L.; Michailova, Anushka P.; McCulloch, Andrew D.; McCullough, A. D. (Principal Investigator)

2003-01-01

The beta-adrenergic signaling pathway regulates cardiac myocyte contractility through a combination of feedforward and feedback mechanisms. We used systems analysis to investigate how the components and topology of this signaling network permit neurohormonal control of excitation-contraction coupling in the rat ventricular myocyte. A kinetic model integrating beta-adrenergic signaling with excitation-contraction coupling was formulated, and each subsystem was validated with independent biochemical and physiological measurements. Model analysis was used to investigate quantitatively the effects of specific molecular perturbations. 3-Fold overexpression of adenylyl cyclase in the model allowed an 85% higher rate of cyclic AMP synthesis than an equivalent overexpression of beta 1-adrenergic receptor, and manipulating the affinity of Gs alpha for adenylyl cyclase was a more potent regulator of cyclic AMP production. The model predicted that less than 40% of adenylyl cyclase molecules may be stimulated under maximal receptor activation, and an experimental protocol is suggested for validating this prediction. The model also predicted that the endogenous heat-stable protein kinase inhibitor may enhance basal cyclic AMP buffering by 68% and increasing the apparent Hill coefficient of protein kinase A activation from 1.0 to 2.0. Finally, phosphorylation of the L-type calcium channel and phospholamban were found sufficient to predict the dominant changes in myocyte contractility, including a 2.6x increase in systolic calcium (inotropy) and a 28% decrease in calcium half-relaxation time (lusitropy). By performing systems analysis, the consequences of molecular perturbations in the beta-adrenergic signaling network may be understood within the context of integrative cellular physiology.

A Combined Very Large Telescope and Gemini Study of the Atmosphere of the Directly Imaged Planet, Beta Pictoris b

NASA Technical Reports Server (NTRS)

Currie, Thayne; Burrows, Adam; Madhusudhan, Nikku; Fukagawa, Misato; Girard, Julien H.; Dawson, Rebekah; Murray-Clay, Ruth; Kenyon, Scott; Kuchner, Marc J.; Matsumura, Soko;

Extending the validation of multi-mode model for anomalous transport to high beta poloidal tokamak scenario in DIII-D

NASA Astrophysics Data System (ADS)

Pankin, A. Y.; Kritz, A. H.; Rafiq, T.; Garofalo, A. M.; Holod, I.; Weiland, J.

2018-05-01

The Multi-Mode Model (MMM7.1) for anomalous transport is tested in predictive modeling of temperature profiles of a high beta poloidal DIII-D discharge. This new H-mode plasma regime, with high beta poloidal and high bootstrap currents, has been studied in DIII-D tokamak discharges [A. Garofalo et al., Nucl. Fusion 55, 123025 (2015)]. The role of instabilities that can drive the anomalous transport described by MMM7.1 is investigated. The temperature profiles for a high beta poloidal DIII-D discharge are computed using the NCLASS model for the neoclassical transport and the Weiland and Electron Temperature Gradient (ETG) components of the MMM7.1 model for the anomalous transport. The neoclassical transport is found to be the main contributor to the ion thermal transport in the plasma core. The contributions from the ion temperature gradient driven modes are found to be important only outside of the internal transport barrier. The magnitudes of the predicted temperature profiles are found to be in a reasonable agreement with experimental profiles. The simulation results approximately reproduce the internal transport barrier in the ion temperature profile but not in the electron temperature profile due to a weak dependence of the ETG driven transport on the Shafranov shift in the ETG component of MMM7.1. Possible effects that can contribute to stabilization of these modes, for example, effects associated with the large beta poloidal such as the Shafranov shift stabilization in the MMM7.1 model, are discussed. It is demonstrated that the E × B flow shear has a relatively small effect in the formation of the internal transport barrier in the high beta poloidal DIII-D discharge 154406. The Shafranov shift (alpha stabilization) and small or reversed magnetic shear profiles are found to be the primary reasons for quenched anomalous transport in this discharge.

Electronic Health Record Patient Portal Adoption by Health Care Consumers: An Acceptance Model and Survey

PubMed Central

2016-01-01

Background The future of health care delivery is becoming more citizen centered, as today’s user is more active, better informed, and more demanding. Worldwide governments are promoting online health services, such as electronic health record (EHR) patient portals and, as a result, the deployment and use of these services. Overall, this makes the adoption of patient-accessible EHR portals an important field to study and understand. Objective The aim of this study is to understand the factors that drive individuals to adopt EHR portals. Methods We applied a new adoption model using, as a starting point, Ventkatesh's Unified Theory of Acceptance and Use of Technology in a consumer context (UTAUT2) by integrating a new construct specific to health care, a new moderator, and new relationships. To test the research model, we used the partial least squares (PLS) causal modelling approach. An online questionnaire was administrated. We collected 360 valid responses. Results The statistically significant drivers of behavioral intention are performance expectancy (beta=.200; t=3.619), effort expectancy (beta=.185; t=2.907), habit (beta=.388; t=7.320), and self-perception (beta=.098; t=2.285). The predictors of use behavior are habit (beta=0.206; t=2.752) and behavioral intention (beta=0.258; t=4.036). The model explained 49.7% of the variance in behavioral intention and 26.8% of the variance in use behavior. Conclusions Our research helps to understand the desired technology characteristics of EHR portals. By testing an information technology acceptance model, we are able to determine what is more valued by patients when it comes to deciding whether to adopt EHR portals or not. The inclusion of specific constructs and relationships related to the health care consumer area also had a significant impact on understanding the adoption of EHR portals. PMID:26935646

Beta-cell function, incretin effect, and incretin hormones in obese youth along the span of glucose tolerance from normal to prediabetes to Type 2 diabetes

USDA-ARS?s Scientific Manuscript database

Using the hyperglycemic and euglycemic clamp, we demonstrated impaired Beta-cell function in obese youth with increasing dysglycemia. Herein we describe oral glucose tolerance test (OGTT)-modeled Beta-cell function and incretin effect in obese adolescents spanning the range of glucose tolerance. Bet...

Business and Education Transition Alliance (BETA): Opening Doors to Career Opportunities for At-Risk Youth.

ERIC Educational Resources Information Center

Stroup, Phillip

1996-01-01

The Business and Education Transition Alliance (BETA) is a model school-to-work transition program that was developed to facilitate the school-to-work transition of at-risk youth in the Boulder Valley School District in Colorado. Among the BETA program's specific goals are the following: increase students' knowledge/understanding of demands of the…

[Molecular and structural-biological analysis of Nicotiana plumbaginifolia mutants for identification of the site of beta-tubulins interaction with dinitroanilines and phosphorotioamidates].

PubMed

Emets, A I; Baiard, U V; Nyporko, A Iu; Swire-Clark, G A; Blium, Ia B

2009-01-01

The identification of point mutation locations on beta-tubulin molecules of amiprophosmethyl- and trifluralin-resistant Nicotiana plumbaginifolia lines have described in the work. It was shown that in the first case this mutation is connected with the substitution ofserine residue on proline in position 248; in the second case--with the substitution of phenilalanine on serine in position 317 of beta-tubulin amino acid sequence. Three-dimensional models of beta-tubulin molecule from Chlamydomonas with well-known location of mutations conferring dinitroaniline- and phosphorotioamidate resistance (substitution of lysine residue to methionine on position 350), and beta-tubulin from Nicotiana plumbaginifolia have been reconstructed. On the basis of analysis of site of interaction with dinitroanilines and phosphorotioamides on Chlamydomonas beta-tubulin molecule it was concluded that the revealed mutations on Nicotiana plumbaginifolia beta-tubulin affect amino acid residues participating in formation of this site.

Comparison of atypical Brachyspira spp. clinical isolates and classic strains in a mouse model of swine dysentery.

PubMed

Burrough, Eric; Strait, Erin; Kinyon, Joann; Bower, Leslie; Madson, Darin; Schwartz, Kent; Frana, Timothy; Songer, J Glenn

2012-12-07

Multiple Brachyspira spp. can colonize the porcine colon, and the presence of the strongly beta-hemolytic Brachyspira hyodysenteriae is typically associated with clinical swine dysentery. Recently, several Brachyspira spp. have been isolated from the feces of pigs with clinical disease suggestive of swine dysentery, yet these isolates were not identified as B. hyodysenteriae by genotypic or phenotypic methods. This study used a mouse model of swine dysentery to compare the pathogenic potential of seventeen different Brachyspira isolates including eight atypical clinical isolates, six typical clinical isolates, the standard strain of B. hyodysenteriae (B204), and reference strains of Brachyspira intermedia and Brachyspira innocens. Results revealed that strongly beta-hemolytic isolates induced significantly greater cecal inflammation than weakly beta-hemolytic isolates regardless of the genetic identification of the isolate, and that strongly beta-hemolytic isolates identified as 'Brachyspira sp. SASK30446' and B. intermedia by PCR produced lesions indistinguishable from those caused by B. hyodysenteriae in this model. Copyright © 2012 Elsevier B.V. All rights reserved.

Prediction of beta-turns from amino acid sequences using the residue-coupled model.

PubMed

Guruprasad, K; Shukla, S

2003-04-01

We evaluated the prediction of beta-turns from amino acid sequences using the residue-coupled model with an enlarged representative protein data set selected from the Protein Data Bank. Our results show that the probability values derived from a data set comprising 425 protein chains yielded an overall beta-turn prediction accuracy 68.74%, compared with 94.7% reported earlier on a data set of 30 proteins using the same method. However, we noted that the overall beta-turn prediction accuracy using probability values derived from the 30-protein data set reduces to 40.74% when tested on the data set comprising 425 protein chains. In contrast, using probability values derived from the 425 data set used in this analysis, the overall beta-turn prediction accuracy yielded consistent results when tested on either the 30-protein data set (64.62%) used earlier or a more recent representative data set comprising 619 protein chains (64.66%) or on a jackknife data set comprising 476 representative protein chains (63.38%). We therefore recommend the use of probability values derived from the 425 representative protein chains data set reported here, which gives more realistic and consistent predictions of beta-turns from amino acid sequences.

A test of the Hall-MHD model: Application to low-frequency upstream waves at Venus

NASA Technical Reports Server (NTRS)

Orlowski, D. S.; Russell, C. T.; Krauss-Varban, D.; Omidi, N.

1994-01-01

Early studies suggested that in the range of parameter space where the wave angular frequency is less than the proton gyrofrequency and the plasma beta, the ratio of the thermal to magnetic pressure, is less than 1 magnetohydrodynamics provides an adequate description of the propagating modes in a plasma. However, recently, Lacombe et al. (1992) have reported significant differences between basic wave characteristics of the specific propagation modes derived from linear Vlasov and Hall-magnetohydrodynamic (MHD) theories even when the waves are only weakly damped. In this paper we compare the magnetic polarization and normalization magnetic compression ratio of ultra low frequency (ULF) upstream waves at Venus with magnetic polarization and normalized magnetic compression ratio derived from both theories. We find that while the 'kinetic' approach gives magnetic polarization and normalized magnetic compression ratio consistent with the data in the analyzed range of beta (0.5 less than beta less than 5) for the fast magnetosonic mode, the same wave characteristics derived from the Hall-MHD model strongly depend on beta and are consistent with the data only at low beta for the fast mode and at high beta for the intermediate mode.

Structural model of the amyloid fibril formed by beta(2)-microglobulin #21-31 fragment based on vibrational spectroscopy.

PubMed

Hiramatsu, Hirotsugu; Goto, Yuji; Naiki, Hironobu; Kitagawa, Teizo

2005-06-08

A structural model of amyloid fibril formed by the #21-31 fragment of beta2-microglobulin is proposed from microscope IR measurements on specifically 13C-labeled peptide fibrils and Raman spectra of the dispersed fibril solution. The 13C-shifted amide frequency indicated the secondary structure of the labeled residues. The IR spectra have demonstrated that the region between F22 and V27 forms the core part with the extended beta-sheet structure. Raman spectra indicated the formation of a dimer with a disulfide bridge between C25 residues.

The pore-lining region of shaker voltage-gated potassium channels: comparison of beta-barrel and alpha-helix bundle models.

PubMed Central

Kerr, I D; Sansom, M S

1997-01-01

Although there is a large body of site-directed mutagenesis data that identify the pore-lining sequence of the voltage-gated potassium channel, the structure of this region remains unknown. We have interpreted the available biochemical data as a set of topological and orientational restraints and employed these restraints to produce molecular models of the potassium channel pore region, H5. The H5 sequence has been modeled either as a tetramer of membrane-spanning beta-hairpins, thus producing an eight-stranded beta-barrel, or as a tetramer of incompletely membrane-spanning alpha-helical hairpins, thus producing an eight-staved alpha-helix bundle. In total, restraints-directed modeling has produced 40 different configurations of the beta-barrel model, each configuration comprising an ensemble of 20 structures, and 24 different configurations of the alpha-helix bundle model, each comprising an ensemble of 24 structures. Thus, over 1300 model structures for H5 have been generated. Configurations have been ranked on the basis of their predicted pore properties and on the extent of their agreement with the biochemical data. This ranking is employed to identify particular configurations of H5 that may be explored further as models of the pore-lining region of the voltage-gated potassium channel pore. Images FIGURE 7 FIGURE 12 PMID:9251779

The oncoprotein Ski acts as an antagonist of transforming growth factor-beta signaling by suppressing Smad2 phosphorylation.

PubMed

Prunier, Celine; Pessah, Marcia; Ferrand, Nathalie; Seo, Su Ryeon; Howe, Philip; Atfi, Azeddine

2003-07-11

The phosphorylation of Smad2 and Smad3 by the transforming growth factor (TGF)-beta-activated receptor kinases and their subsequent heterodimerization with Smad4 and translocation to the nucleus form the basis for a model how Smad proteins work to transmit TGF-beta signals. The transcriptional activity of Smad2-Smad4 or Smad3-Smad4 complexes can be limited by the corepressor Ski, which is believed to interact with Smad complexes on TGF-beta-responsive promoters and represses their ability to activate TGF-beta target genes by assembling on DNA a repressor complex containing histone deacetylase. Here we show that Ski can block TGF-beta signaling by interfering with the phosphorylation of Smad2 and Smad3 by the activated TGF-beta type I receptor. Furthermore, we demonstrate that overexpression of Ski induces the assembly of Smad2-Smad4 and Smad3-Smad4 complexes independent of TGF-beta signaling. The ability of Ski to engage Smad proteins in nonproductive complexes provides new insights into the molecular mechanism used by Ski for disabling TGF-beta signaling.

Uterine leiomyoma is associated with a polymorphism in the interleukin 1-beta gene.

PubMed

Pietrowski, Detlef; Thewes, Roberta; Sator, Michael; Denschlag, Dominik; Keck, Christoph; Tempfer, Clemens

2009-08-01

To investigate whether polymorphisms in the interleukin-1beta (IL-1beta) gene are associated with uterine leiomyoma. Case-control study in a collective of 131 patients and 280 controls. Genotyping of the IL-1beta-511 and IL-1beta-3954 polymorphism was performed by PCR amplification and subsequent RFLP analysis. A significant difference in the allele frequencies of the IL-1beta-511 C

Prevalence and prognostic significance of adrenergic escape during chronic beta-blocker therapy in chronic heart failure.

PubMed

Frankenstein, Lutz; Zugck, Christian; Schellberg, Dieter; Nelles, Manfred; Froehlich, Hanna; Katus, Hugo; Remppis, Andrew

2009-02-01

Like aldosterone escape to ACE-inhibitors, adrenergic escape (AE) to beta-blockers appears conceivable in chronic heart failure (CHF), as generalized systemic neurohumoral activation has been described as the pathophysiological basis of this syndrome. The aim of this study was to examine the prevalence and prognostic value of AE with respect to different beta-blocker agents and doses. This was a prospective, observational study of 415 patients with systolic CHF receiving chronic stable beta-blocker therapy. AE was defined by norepinephrine levels above the upper limit of normal. Irrespective of the individual beta-blocker agents used and the dose equivalent taken, the prevalence of AE was 31-39%. Norepinephrine levels neither correlated with heart rate (r=0.02; 95% CI: -0.08-0.11; P=0.74) nor were they related to underlying rhythm (P=0.09) or the individual beta-blocker agent used (P=0.87). The presence of AE was a strong and independent indicator of mortality (adjusted HR: 1.915; 95% CI: 1.387-2.645; chi2: 15.60). We verified the presence of AE in CHF patients on chronic stable beta-blocker therapy, irrespective of the individual beta-blocker agent and the dose equivalent. As AE might indicate therapeutic failure, the determination of AE could help to identify those patients with CHF that might benefit from more aggressive treatment modalities. Heart rate, however, is not a surrogate for adrenergic escape.

A modelling approach to assessing the timescale uncertainties in proxy series with chronological errors

NASA Astrophysics Data System (ADS)

Divine, D. V.; Godtliebsen, F.; Rue, H.

2012-01-01

The paper proposes an approach to assessment of timescale errors in proxy-based series with chronological uncertainties. The method relies on approximation of the physical process(es) forming a proxy archive by a random Gamma process. Parameters of the process are partly data-driven and partly determined from prior assumptions. For a particular case of a linear accumulation model and absolutely dated tie points an analytical solution is found suggesting the Beta-distributed probability density on age estimates along the length of a proxy archive. In a general situation of uncertainties in the ages of the tie points the proposed method employs MCMC simulations of age-depth profiles yielding empirical confidence intervals on the constructed piecewise linear best guess timescale. It is suggested that the approach can be further extended to a more general case of a time-varying expected accumulation between the tie points. The approach is illustrated by using two ice and two lake/marine sediment cores representing the typical examples of paleoproxy archives with age models based on tie points of mixed origin.

Influence of beta-radiation sterilisation in properties of new chitosan/soybean protein isolate membranes for guided bone regeneration.

PubMed

Silva, R M; Elvira, C; Mano, J F; San Román, J; Reis, R L

2004-04-01

Novel chitosan (cts) and soybean protein isolate (SI) blended membranes were prepared. These membranes were produced by solvent casting. Besides combining the advantages of both materials, cts/SI membranes exhibit a biphasic structure that will eventually originate in situ porous formation, through a two-step degradation mechanism. In this particular work the effect of beta-radiation over the properties of these membranes was evaluated. beta-radiation sterilisation was performed at three different doses (25, 50 and 100 kGy) and eventual surface chemical changes were evaluated by Fourier transformed infrared--with attenuated total reflection and contact angle measurements. Moreover, eventual bulk properties changes due to beta-radiation were assessed by means of mechanical tensile tests and water uptake measurements. In general, no substantial changes were detected on the studied properties, with the exception of the surface energy that was found to be slightly increased for higher applied doses.

Topographic Beta Spiral and Onshore Intrusion of the Kuroshio Current

NASA Astrophysics Data System (ADS)

Yang, De-Zhou; Huang, Rui Xin; Yin, Bao-shu; Feng, Xing-Ru; Chen, Hai-ying; Qi, Ji-Feng; Xu, Ling-jing; Shi, Yun-long; Cui, Xuan; Gao, Guan-Dong; Benthuysen, Jessica A.

2018-01-01

The Kuroshio intrusion plays a vitally important role in carrying nutrients to marginal seas. However, the key mechanism leading to the Kuroshio intrusion remains unclear. In this study we postulate a mechanism: when the Kuroshio runs onto steep topography northeast of Taiwan, the strong inertia gives rise to upwelling over topography, leading to a left-hand spiral in the stratified ocean. This is called the topographic beta spiral, which is a major player regulating the Kuroshio intrusion; this spiral can be inferred from hydrographic surveys. In the world oceans, the topographic beta spirals can be induced by upwelling generated by strong currents running onto steep topography. This is a vital mechanism regulating onshore intruding flow and the cross-shelf transport of energy and nutrients from the Kuroshio Current to the East China Sea. This topographic beta spiral reveals a long-term missing link between the oceanic general circulation theory and shelf dynamic theory.

First flavor-tagged determination of bounds on mixing-induced CP violation in Bs0 --> J/psiphi decays.

PubMed

Aaltonen, T; Adelman, J; Akimoto, T; Albrow, M G; Alvarez González, B; Amerio, S; Amidei, D; Anastassov, A; Annovi, A; Antos, J; Aoki, M; Apollinari, G; Apresyan, A; Arisawa, T; Artikov, A; Ashmanskas, W; Attal, A; Aurisano, A; Azfar, F; Azzi-Bacchetta, P; Azzurri, P; Bacchetta, N; Badgett, W; Barbaro-Galtieri, A; Barnes, V E; Barnett, B A; Baroiant, S; Bartsch, V; Bauer, G; Beauchemin, P-H; Bedeschi, F; Bednar, P; Behari, S; Bellettini, G; Bellinger, J; Belloni, A; Benjamin, D; Beretvas, A; Beringer, J; Berry, T; Bhatti, A; Binkley, M; Bisello, D; Bizjak, I; Blair, R E; Blocker, C; Blumenfeld, B; Bocci, A; Bodek, A; Boisvert, V; Bolla, G; Bolshov, A; Bortoletto, D; Boudreau, J; Boveia, A; Brau, B; Bridgeman, A; Brigliadori, L; Bromberg, C; Brubaker, E; Budagov, J; Budd, H S; Budd, S; Burkett, K; Busetto, G; Bussey, P; Buzatu, A; Byrum, K L; Cabrera, S; Campanelli, M; Campbell, M; Canelli, F; Canepa, A; Carlsmith, D; Carosi, R; Carrillo, S; Carron, S; Casal, B; Casarsa, M; Castro, A; Catastini, P; Cauz, D; Cavalli-Sforza, M; Cerri, A; Cerrito, L; Chang, S H; Chen, Y C; Chertok, M; Chiarelli, G; Chlachidze, G; Chlebana, F; Cho, K; Chokheli, D; Chou, J P; Choudalakis, G; Chuang, S H; Chung, K; Chung, W H; Chung, Y S; Ciobanu, C I; Ciocci, M A; Clark, A; Clark, D; Compostella, G; Convery, M E; Conway, J; Cooper, B; Copic, K; Cordelli, M; Cortiana, G; Crescioli, F; Cuenca Almenar, C; Cuevas, J; Culbertson, R; Cully, J C; Dagenhart, D; Datta, M; Davies, T; de Barbaro, P; De Cecco, S; Deisher, A; De Lentdecker, G; De Lorenzo, G; Dell'Orso, M; Demortier, L; Deng, J; Deninno, M; De Pedis, D; Derwent, P F; Di Giovanni, G P; Dionisi, C; Di Ruzza, B; Dittmann, J R; D'Onofrio, M; Donati, S; Dong, P; Donini, J; Dorigo, T; Dube, S; Efron, J; Erbacher, R; Errede, D; Errede, S; Eusebi, R; Fang, H C; Farrington, S; Fedorko, W T; Feild, R G; Feindt, M; Fernandez, J P; Ferrazza, C; Field, R; Flanagan, G; Forrest, R; Forrester, S; Franklin, M; Freeman, J C; Furic, I; Gallinaro, M; Galyardt, J; Garberson, F; Garcia, J E; Garfinkel, A F; Genser, K; Gerberich, H; Gerdes, D; Giagu, S; Giakoumopolou, V; Giannetti, P; Gibson, K; Gimmell, J L; Ginsburg, C M; Giokaris, N; Giordani, M; Giromini, P; Giunta, M; Giurgiu, G; Glagolev, V; Glenzinski, D; Gold, M; Goldschmidt, N; Golossanov, A; Gomez, G; Gomez-Ceballos, G; Goncharov, M; González, O; Gorelov, I; Goshaw, A T; Goulianos, K; Gresele, A; Grinstein, S; Grosso-Pilcher, C; Grundler, U; Guimaraes da Costa, J; Gunay-Unalan, Z; Haber, C; Hahn, K; Hahn, S R; Halkiadakis, E; Hamilton, A; Han, B-Y; Han, J Y; Handler, R; Happacher, F; Hara, K; Hare, D; Hare, M; Harper, S; Harr, R F; Harris, R M; Hartz, M; Hatakeyama, K; Hauser, J; Hays, C; Heck, M; Heijboer, A; Heinemann, B; Heinrich, J; Henderson, C; Herndon, M; Heuser, J; Hewamanage, S; Hidas, D; Hill, C S; Hirschbuehl, D; Hocker, A; Hou, S; Houlden, M; Hsu, S-C; Huffman, B T; Hughes, R E; Husemann, U; Huston, J; Incandela, J; Introzzi, G; Iori, M; Ivanov, A; Iyutin, B; James, E; Jayatilaka, B; Jeans, D; Jeon, E J; Jindariani, S; Johnson, W; Jones, M; Joo, K K; Jun, S Y; Jung, J E; Junk, T R; Kamon, T; Kar, D; Karchin, P E; Kato, Y; Kephart, R; Kerzel, U; Khotilovich, V; Kilminster, B; Kim, D H; Kim, H S; Kim, J E; Kim, M J; Kim, S B; Kim, S H; Kim, Y K; Kimura, N; Kirsch, L; Klimenko, S; Klute, M; Knuteson, B; Ko, B R; Koay, S A; Kondo, K; Kong, D J; Konigsberg, J; Korytov, A; Kotwal, A V; Kraus, J; Kreps, M; Kroll, J; Krumnack, N; Kruse, M; Krutelyov, V; Kubo, T; Kuhlmann, S E; Kuhr, T; Kulkarni, N P; Kusakabe, Y; Kwang, S; Laasanen, A T; Labarga, L; Lai, S; Lami, S; Lammel, S; Lancaster, M; Lander, R L; Lannon, K; Lath, A; Latino, G; Lazzizzera, I; LeCompte, T; Lee, J; Lee, J; Lee, Y J; Lee, S W; Lefèvre, R; Leonardo, N; Leone, S; Levy, S; Lewis, J D; Lin, C; Lin, C S; Linacre, J; Lindgren, M; Lipeles, E; Lister, A; Litvintsev, D O; Liu, C; Liu, T; Lockyer, N S; Loginov, A; Loreti, M; Lovas, L; Lu, R-S; Lucchesi, D; Lueck, J; Luci, C; Lujan, P; Lukens, P; Lungu, G; Lyons, L; Lys, J; Lysak, R; Lytken, E; Mack, P; MacQueen, D; Madrak, R; Maeshima, K; Makhoul, K; Maki, T; Maksimovic, P; Malde, S; Malik, S; Manca, G; Manousakis, A; Margaroli, F; Marino, C; Marino, C P; Martin, A; Martin, M; Martin, V; Martínez, M; Martínez-Ballarín, R; Maruyama, T; Mastrandrea, P; Masubuchi, T; Mattson, M E; Mazzanti, P; McFarland, K S; McIntyre, P; McNulty, R; Mehta, A; Mehtala, P; Menzemer, S; Menzione, A; Merkel, P; Mesropian, C; Messina, A; Miao, T; Miladinovic, N; Miles, J; Miller, R; Mills, C; Milnik, M; Mitra, A; Mitselmakher, G; Miyake, H; Moed, S; Moggi, N; Moon, C S; Moore, R; Morello, M; Movilla Fernandez, P; Mülmenstädt, J; Mukherjee, A; Muller, Th; Mumford, R; Murat, P; Mussini, M; Nachtman, J; Nagai, Y; Nagano, A; Naganoma, J; Nakamura, K; Nakano, I; Napier, A; Necula, V; Neu, C; Neubauer, M S; Nielsen, J; Nodulman, L; Norman, M; Norniella, O; Nurse, E; Oh, S H; Oh, Y D; Oksuzian, I; Okusawa, T; Oldeman, R; Orava, R; Osterberg, K; Pagan Griso, S; Pagliarone, C; Palencia, E; Papadimitriou, V; Papaikonomou, A; Paramonov, A A; Parks, B; Pashapour, S; Patrick, J; Pauletta, G; Paulini, M; Paus, C; Pellett, D E; Penzo, A; Phillips, T J; Piacentino, G; Piedra, J; Pinera, L; Pitts, K; Plager, C; Pondrom, L; Portell, X; Poukhov, O; Pounder, N; Prakoshyn, F; Pronko, A; Proudfoot, J; Ptohos, F; Punzi, G; Pursley, J; Rademacker, J; Rahaman, A; Ramakrishnan, V; Ranjan, N; Redondo, I; Reisert, B; Rekovic, V; Renton, P; Rescigno, M; Richter, S; Rimondi, F; Ristori, L; Robson, A; Rodrigo, T; Rogers, E; Rolli, S; Roser, R; Rossi, M; Rossin, R; Roy, P; Ruiz, A; Russ, J; Rusu, V; Saarikko, H; Safonov, A; Sakumoto, W K; Salamanna, G; Saltó, O; Santi, L; Sarkar, S; Sartori, L; Sato, K; Savoy-Navarro, A; Scheidle, T; Schlabach, P; Schmidt, E E; Schmidt, M A; Schmidt, M P; Schmitt, M; Schwarz, T; Scodellaro, L; Scott, A L; Scribano, A; Scuri, F; Sedov, A; Seidel, S; Seiya, Y; Semenov, A; Sexton-Kennedy, L; Sfyrla, A; Shalhout, S Z; Shapiro, M D; Shears, T; Shepard, P F; Sherman, D; Shimojima, M; Shochet, M; Shon, Y; Shreyber, I; Sidoti, A; Sinervo, P; Sisakyan, A; Slaughter, A J; Slaunwhite, J; Sliwa, K; Smith, J R; Snider, F D; Snihur, R; Soderberg, M; Soha, A; Somalwar, S; Sorin, V; Spalding, J; Spinella, F; Spreitzer, T; Squillacioti, P; Stanitzki, M; St Denis, R; Stelzer, B; Stelzer-Chilton, O; Stentz, D; Strologas, J; Stuart, D; Suh, J S; Sukhanov, A; Sun, H; Suslov, I; Suzuki, T; Taffard, A; Takashima, R; Takeuchi, Y; Tanaka, R; Tecchio, M; Teng, P K; Terashi, K; Thom, J; Thompson, A S; Thompson, G A; Thomson, E; Tipton, P; Tiwari, V; Tkaczyk, S; Toback, D; Tokar, S; Tollefson, K; Tomura, T; Tonelli, D; Torre, S; Torretta, D; Tourneur, S; Trischuk, W; Tu, Y; Turini, N; Ukegawa, F; Uozumi, S; Vallecorsa, S; van Remortel, N; Varganov, A; Vataga, E; Vázquez, F; Velev, G; Vellidis, C; Veszpremi, V; Vidal, M; Vidal, R; Vila, I; Vilar, R; Vine, T; Vogel, M; Volobouev, I; Volpi, G; Würthwein, F; Wagner, P; Wagner, R G; Wagner, R L; Wagner-Kuhr, J; Wagner, W; Wakisaka, T; Wallny, R; Wang, S M; Warburton, A; Waters, D; Weinberger, M; Wester, W C; Whitehouse, B; Whiteson, D; Wicklund, A B; Wicklund, E; Williams, G; Williams, H H; Wilson, P; Winer, B L; Wittich, P; Wolbers, S; Wolfe, C; Wright, T; Wu, X; Wynne, S M; Yagil, A; Yamamoto, K; Yamaoka, J; Yamashita, T; Yang, C; Yang, U K; Yang, Y C; Yao, W M; Yeh, G P; Yoh, J; Yorita, K; Yoshida, T; Yu, G B; Yu, I; Yu, S S; Yun, J C; Zanello, L; Zanetti, A; Zaw, I; Zhang, X; Zheng, Y; Zucchelli, S

2008-04-25

This Letter describes the first determination of bounds on the CP-violation parameter 2beta(s) using B(s)(0) decays in which the flavor of the bottom meson at production is identified. The result is based on approximately 2000 B(s)(0)-->J/psiphi decays reconstructed in a 1.35 fb(-1) data sample collected with the CDF II detector using pp collisions produced at the Fermilab Tevatron. We report confidence regions in the two-dimensional space of 2beta(s) and the decay-width difference DeltaGamma. Assuming the standard model predictions of 2beta(s) and DeltaGamma, the probability of a deviation as large as the level of the observed data is 15%, corresponding to 1.5 Gaussian standard deviations.

Sevoflurane Induces Coherent Slow-Delta Oscillations in Rats

PubMed Central

Guidera, Jennifer A.; Taylor, Norman E.; Lee, Justin T.; Vlasov, Ksenia Y.; Pei, JunZhu; Stephen, Emily P.; Mayo, J. Patrick; Brown, Emery N.; Solt, Ken

2017-01-01

Although general anesthetics are routinely administered to surgical patients to induce loss of consciousness, the mechanisms underlying anesthetic-induced unconsciousness are not fully understood. In rats, we characterized changes in the extradural EEG and intracranial local field potentials (LFPs) within the prefrontal cortex (PFC), parietal cortex (PC), and central thalamus (CT) in response to progressively higher doses of the inhaled anesthetic sevoflurane. During induction with a low dose of sevoflurane, beta/low gamma (12–40 Hz) power increased in the frontal EEG and PFC, PC and CT LFPs, and PFC–CT and PFC–PFC LFP beta/low gamma coherence increased. Loss of movement (LOM) coincided with an abrupt decrease in beta/low gamma PFC–CT LFP coherence. Following LOM, cortically coherent slow-delta (0.1–4 Hz) oscillations were observed in the frontal EEG and PFC, PC and CT LFPs. At higher doses of sevoflurane sufficient to induce loss of the righting reflex, coherent slow-delta oscillations were dominant in the frontal EEG and PFC, PC and CT LFPs. Dynamics similar to those observed during induction were observed as animals emerged from sevoflurane anesthesia. We conclude that the rat is a useful animal model for sevoflurane-induced EEG oscillations in humans, and that coherent slow-delta oscillations are a correlate of sevoflurane-induced behavioral arrest and loss of righting in rats. PMID:28725184

Diarrhea, stimulation and growth predict neurodevelopment in young North Indian children.

PubMed

Kvestad, Ingrid; Taneja, Sunita; Hysing, Mari; Kumar, Tivendra; Bhandari, Nita; Strand, Tor A

2015-01-01

Infants and young children in low to middle-income countries are at risk for adverse neurodevelopment due to multiple risk factors. In this study, we sought to identify stimulation and learning opportunities, growth, and burden of respiratory infections and diarrhea as predictors for neurodevelopment. We visited 422 North Indian children 6 to 30 months old weekly for six months. Childhood illnesses were assessed biweekly. At end study, we assessed neurodevelopment using the Ages and Stages Questionnaire 3rd ed. (ASQ-3) and gathered information on stimulation and learning opportunities. We identified predictors for ASQ-3 scores in multiple linear and logistic regression models. We were able to explain 30.5% of the variation in the total ASQ-3 score by the identified predictors. When adjusting for child characteristics and annual family income, stimulation and learning opportunities explained most of the variation by 25.1%. Height for age (standardized beta: 0.12, p<.05) and weight for height z-scores (std. beta: 0.09, p<.05) were positively associated with the total ASQ-3 score, while number of days with diarrhea was negatively associated with these scores (std. beta: -0.13, p<0.01). Our results support the importance of early child stimulation and general nutrition for child development. Our study also suggests that diarrhea is an additional risk factor for adverse neurodevelopment in vulnerable children.

[Protection and bidirectional effect of rhubarb anthraquinone and tannins for rats' liver].

PubMed

Qin, Lu-shan; Zhao, Hai-ping; Zhao, Yan-ling; Ma, Zhi-jiel; Zeng, Ling-na; Zhang, Ya-ming; Zhang, Ping; Yan, Dan; Bai, Zhao-fang; Li, Yue; Hao, Qing-xiu; Zhao, Kui-jun; Wang, Jia-bo; Xiao, Xiao-he

2014-06-01

To compare the bidirectional effect of rhubarb total anthraquinone (TA) and total tannins (TT) on rats' liver. One hundred rats were randomly divided into 10 groups, i.e., the blank group, the model group, the blank + high dose TA group, the blank +low dose TA group, the blank + high dose TT group, the blank + low dose TT group, the model + high dose TA group, the model + low dose TA group, the model +high dose TT group, and the model + low dose TT group, 10 in each group. The carbon tetrachloride (CCI4) was used to prepare the acute liver injury rat model. TA and TT of rhubarb (at 5.40 g crude drugs/kg and 14.69 g crude drugs/kg) were intragastrically administrated to rats in all groups except the blank group and the model group, once daily for 6 successive days.The general state of rats, biochemical indices such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), laminin (LN), hyaluronic acid (HA), transforming growth factor beta1 (TGF-beta1), as well pathological results of rat liver tissues. Finally the protection laws of TA and TT for rats' liver were analyzed using factor analysis. Compared with the blank control group, all biochemical indices increased in the blank group (P < 0.05, P < 0.01). HA also increased in the blank + high dose TA group; AST, ALT, and HA also increased in the blank +high dose TT group (P < 0.05). Compared with the model group, AST, ALT, ALP, HA, and TGF-beta1 significantly decreased in the model + low dose TA group, the model + high dose TA group, the model + low dose TT group (P < 0.05, P < 0.01). Serum AST, ALT, and ALP also decreased in the model + high dose TT group (P < 0.05, P < 0.01). Pathological results showed that mild swollen liver cells in the model + high dose TA group. Fatty degeneration and fragmental necrosis around the central veins occurred in the blank + high dose TA group. The pathological injury was inproved in the model +low dose TA group. Two common factors, liver fibrosis and liver cell injury, were extracted by using factor analysis. TA showed stronger improvement of the two common factors than TT. Rhubarb TA and TT showed protective and harmful effects on rats' liver. At an equivalent dosage, TA had better liver protection than TT. High dose TT played a role in liver injury to some extent.

Investigation of the beta-damascenone level in fresh and aged commercial beers.

PubMed

Chevance, Fabienne; Guyot-Declerck, Christine; Dupont, Jérôme; Collin, Sonia

2002-06-19

This study investigated the increase of beta-damascenone content during aging in a variety of commercial Belgian beers. Quantities detected in fresh beers were generally low (from 6 ng/g to 25 ng/g). After 5 days at 40 degrees C, the level increased (to as much as 210 ng/g) in most of the beers studied, according to the type of beer. Further experiments showed that wort initially contains large quantities of beta-damascenone (450 ng/g), but that degradation of the compound during fermentation accounts for the low concentrations observed in fresh beers. Production during beer aging can be partially explained by acid hydrolysis of glycosides.

Effects of beta-blockers and nicardipine on oxotremorine-induced tremor in common marmosets.

PubMed

Mitsuda, M; Nomoto, M; Iwata, S

1999-10-01

Effects of beta-blockers (propranolol, arotinolol and nipradilol) and a Ca2+ channel blocker (nicardipine) on oxotremorine-induced tremor were studied in common marmosets. Generalized tremor was elicited by an intraperitoneal administration of 0.25 mg/kg oxotremorine. Intensity of the tremor was classified into 7 degrees, and it was evaluated every 10 min. The total intensity of oxotremorine-induced tremor for each drug was expressed as "points", which were the sum of tremor intensity scores evaluated every 10 min up to 190 min following the administration of oxotremorine. Beta-blockers significantly suppressed the tremor. On the other hand, the Ca2+ channel blocker exacerbated the tremor.

A comparison of general and ambulance specific stressors: predictors of job satisfaction and health problems in a nationwide one-year follow-up study of Norwegian ambulance personnel.

PubMed

Sterud, Tom; Hem, Erlend; Lau, Bjørn; Ekeberg, Oivind

2011-03-31

To address the relative importance of general job-related stressors, ambulance specific stressors and individual characteristics in relation to job satisfaction and health complaints (emotional exhaustion, psychological distress and musculoskeletal pain) among ambulance personnel. A nationwide prospective questionnaire survey of ambulance personnel in operational duty at two time points (n = 1180 at baseline, T1 and n = 298 at one-year follow up, T2). The questionnaires included the Maslach Burnout Inventory, The Job Satisfaction Scale, Hopkins Symptom Checklist (SCL-10), Job Stress Survey, the Norwegian Ambulance Stress Survey and the Basic Character Inventory. Overall, 42 out of the possible 56 correlations between job stressors at T1 and job satisfaction and health complaints at T2 were statistically significant. Lower job satisfaction at T2 was predicted by frequency of lack of leader support and severity of challenging job tasks. Emotional exhaustion at T2 was predicted by neuroticism, frequency of lack of support from leader, time pressure, and physical demands. Adjusted for T1 levels, emotional exhaustion was predicted by neuroticism (beta = 0.15, p < .05) and time pressure (beta = 0.14, p < 0.01). Psychological distress at T2 was predicted by neuroticism and lack of co-worker support. Adjusted for T1 levels, psychological distress was predicted by neuroticism (beta = 0.12, p < .05). Musculoskeletal pain at T2 was predicted by, higher age, neuroticism, lack of co-worker support and severity of physical demands. Adjusted for T1 levels, musculoskeletal pain was predicted neuroticism, and severity of physical demands (beta = 0.12, p < .05). Low job satisfaction at T2 was predicted by general work-related stressors, whereas health complaints at T2 were predicted by both general work-related stressors and ambulance specific stressors. The personality variable neuroticism predicted increased complaints across all health outcomes.

Discovery of an imidazopyridine-containing 1,4-benzodiazepine nonpeptide vitronectin receptor (alpha v beta 3) antagonist with efficacy in a restenosis model.

PubMed

Keenan, R M; Lago, M A; Miller, W H; Ali, F E; Cousins, R D; Hall, L B; Hwang, S M; Jakas, D R; Kwon, C; Louden, C; Nguyen, T T; Ohlstein, E H; Rieman, D J; Ross, S T; Samanen, J M; Smith, B R; Stadel, J; Takata, D T; Vickery, L; Yuan, C C; Yue, T L

1998-11-17

In the 3-oxo-1,4-benzodiazepine-2-acetic acid series of vitronectin receptor (alpha v beta 3) antagonists, a compound containing an imidazopyridine arginine mimetic was discovered which had sufficient potency and i.v. pharmacokinetics for demonstration of efficacy in a rat restenosis model.

Anti-inflammatory, analgesic and ulcerogenic properties of S-(+)-ibuproxam, racemic ibuproxam-beta-cyclodextrin and S-(+)-ibuproxam-beta-cyclodextrin.

PubMed

Bole-Vunduk, B; Verhnjak, K; Zmitek, J

1996-11-01

The anti-inflammatory, analgesic and gastric mucosal damage-inducing activities of S-(+)-ibuproxam, and S-(+)-ibuproxam-beta-cyclodextrin, new propionic acid derivatives, and racemic ibuproxam-beta-cyclodextrin were investigated in three animal models and compared with those of racemic ibuproxam, racemic ibuprofen and its optical enantiomer S-(+)-ibuprofen. The anti-inflammatory activities of racemic ibuprofen, S-(+)-ibuprofen and racemic ibuproxam in carrageenan-induced paw oedema in rats were almost equipotent and slightly greater than those of S-(+)-ibuproxam and S-(+)-ibuproxam-beta-cyclodextrin, and significantly greater than that of racemic ibuproxam-beta-cyclodextrin. In abdominal constriction tests in mice, the analgesic effects of racemic ibuproxam, S-(+)-ibuproxam, racemic ibuproxam-beta-cyclodextrin and S-(+)-ibuproxam-beta-cyclodextrin were significantly less pronounced than those of racemic ibuprofen and S-(+)-ibuprofen. Ulcerogenic activity of S-(+)-ibuproxam-beta-cyclodextrin in rats was found to be significantly weaker than that of racemic ibuproxam-beta-cyclodextrin, racemic ibuproxam and S-(+)-ibuproxam and, most notably, weaker than those of racemic ibuprofen and S-(+)ibuprofen. These results indicate that S-(+)-ibuproxam-beta-cyclodextrin could be a novel potent anti-inflammatory and analgesic agent with a therapeutic index more favourable than that of the classical non-steroid anti-inflammatory drugs ibuprofen and ibuproxam.

Treatment with unsaponifiable extracts of avocado and soybean increases TGF-beta1 and TGF-beta2 levels in canine joint fluid.

PubMed

Altinel, Levent; Saritas, Z Kadir; Kose, Kamil Cagri; Pamuk, Kamuran; Aksoy, Yusuf; Serteser, Mustafa

2007-02-01

Avocado and soya unsaponifiables (ASU) are plant extracts used as a slow-acting antiarthritic agent. ASU stimulate the synthesis of matrix components by chondrocytes, probably by increasing the production of transforming growth factor-beta (TGF-beta). TGF-beta is expressed by chondrocytes and osteoblasts and is present in cartilage matrix. This study investigates the effect of ASU treatment on the levels of two isoforms of TGFbeta, TGF-beta1 and TGF-beta2, in the knee joint fluid using a canine model. Twenty-four outbred dogs were divided into three groups. The control animals were given a normal diet, while the treated animals were given 300 mg ASU every three days or every day. Joint fluid samples were obtained prior to treatment, and at the end of every month (up to three months). TGF-beta1 and TGF-beta2 levels were measured using a quantitative sandwich enzyme immunoassay technique. ASU treatment caused an increase in TGF-beta1 and TGF-beta2 levels in the joint fluid when compared to controls. The different doses did not cause a significant difference in joint fluid TGF levels. TGF-beta1 levels in the treated animals reached maximum values at the end of the second month and then decreased after the third month, while TGF-beta2 levels showed a marginal increase during the first two months, followed by a marked increase at the end of the third month. In conclusion, ASU increased both TGF-beta1 and TGF-beta2 levels in knee joint fluid.

The order of administration of macrolides and beta-lactams may impact the outcomes of hospitalized patients with community-acquired pneumonia: results from the community-acquired pneumonia organization.

PubMed

Peyrani, Paula; Wiemken, Timothy L; Metersky, Mark L; Arnold, Forest W; Mattingly, William A; Feldman, Charles; Cavallazzi, Rodrigo; Fernandez-Botran, Rafael; Bordon, Jose; Ramirez, Julio A

2018-01-01

The beneficial effect of macrolides for the treatment of community-acquired pneumonia (CAP) in combination with beta-lactams may be due to their anti-inflammatory activity. In patients with pneumococcal meningitis, the use of steroids improves outcomes only if they are administered before beta-lactams. The objective of this study was to compare outcomes in hospitalized patients with CAP when macrolides were administered before, simultaneously with, or after beta-lactams. Secondary data analysis of the Community-Acquired Pneumonia Organization (CAPO) International Cohort Study database. Study groups were defined based on the sequence of administration of macrolides and beta-lactams. The study outcomes were time to clinical stability (TCS), length of stay (LOS) and in-hospital mortality. Accelerated failure time models were used to evaluate the adjusted impact of sequential antibiotic administration and time-to-event outcomes, while a logistic regression model was used to evaluate their adjusted impact on mortality. A total of 99 patients were included in the macrolide before group and 305 in the macrolide after group. Administration of a macrolide before a beta-lactam compared to after a beta-lactam reduced TCS (3 vs. 4 days, p = .011), LOS (6 vs. 7 days, p = .002) and mortality (3 vs. 7.2%, p = .228). The administration of macrolides before beta-lactams was associated with a statistically significant decrease in TCS and LOS and a non-statistically significant decrease in mortality. The beneficial effect of macrolides in hospitalized patient with CAP may occur only if administered before beta-lactams.

Combining and comparing neutrinoless double beta decay experiments using different nuclei

NASA Astrophysics Data System (ADS)

Bergström, Johannes

2013-02-01

We perform a global fit of the most relevant neutrinoless double beta decay experiments within the standard model with massive Majorana neutrinos. Using Bayesian inference makes it possible to take into account the theoretical uncertainties on the nuclear matrix elements in a fully consistent way. First, we analyze the data used to claim the observation of neutrinoless double beta decay in 76Ge, and find strong evidence (according to Jeffrey's scale) for a peak in the spectrum and moderate evidence for that the peak is actually close to the energy expected for the neutrinoless decay. We also find a significantly larger statistical error than the original analysis, which we include in the comparison with other data. Then, we statistically test the consistency between this claim with that of recent measurements using 136Xe. We find that the two data sets are about 40 to 80 times more probable under the assumption that they are inconsistent, depending on the nuclear matrix element uncertainties and the prior on the smallest neutrino mass. Hence, there is moderate to strong evidence of incompatibility, and for equal prior probabilities the posterior probability of compatibility is between 1.3% and 2.5%. If one, despite such evidence for incompatibility, combines the two data sets, we find that the total evidence of neutrinoless double beta decay is negligible. If one ignores the claim, there is weak evidence against the existence of the decay. We also perform approximate frequentist tests of compatibility for fixed ratios of the nuclear matrix elements, as well as of the no signal hypothesis. Generalization to other sets of experiments as well as other mechanisms mediating the decay is possible.

Placental lactogen secretion during prolonged-pregnancy in the rat: the ovary plays a pivotal role in the control of placental function.

PubMed

Shiota, K; Furuyama, N; Takahashi, M

1991-10-01

The serum of rats at mid-pregnancy contains at least 2 distinct placental lactogen (PL)-like substances tentatively termed placental lactogen-alpha (PL-alpha) and placental lactogen-beta (PL-beta) (Endocrinol Japon 38: 533-540, 1991). We have investigated the secretory patterns of three placental lactogens (PL-alpha, PL-beta and placental lactogen-II) during normal pregnancy and in two prolonged-pregnancy models. Pregnancy was prolonged by the introduction of new corpora lutea by inducing ovulation on day 15 of pregnancy by successive treatments with PMSG (30 IU/rat, sc on day 12) and hCG (10 IU/rat, iv on day 14), and in the second model by progesterone implants on day 15 of pregnancy. During normal pregnancy, each of the 3 PLs exhibited only one secretory peak in the serum; PL-alpha and PL-beta on day 12 and placental lactogen II (PL-II) on day 20. Interestingly, in the rats with new sets of corpora lutea, serum PL-alpha and PL-beta levels began to increase again on day 18 and showed peaks on day 20 for PL-alpha and on day 22 for PL-beta. In this model, the initiation of PL-II secretion was not affected, but high levels were maintained until day 26, when parturition occurred. In rats receiving either PMSG or hCG, the secretory patterns of the PLs were similar to as those during normal pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)

Microporous pure beta-tricalcium phosphate implants for press-fit fixation of anterior cruciate ligament grafts: strength and healing in a sheep model.

PubMed

Mayr, Hermann O; Dietrich, Markwart; Fraedrich, Franz; Hube, Robert; Nerlich, Andreas; von Eisenhart-Rothe, Rüdiger; Hein, Werner; Bernstein, Anke

2009-09-01

A sheep study was conducted to test a press-fit technique using microporous pure beta-tricalcium phosphate (beta-TCP) dowels for fixation of the anterior cruciate ligament (ACL) graft. Microporous (5 mum) cylindrical plugs of beta-TCP (diameter, 7 mm; length, 25 mm) with interconnecting pores were used. The material featured a novel configuration of structure and surface geometry. Implants were tested by use of press-fit fixation of ACL grafts with and without bone blocks in 42 sheep over a period of 24 weeks. Biomechanical, radiologic, histologic, and immunohistochemical evaluations were performed. In load-to-failure tests at 6, 12, and 24 weeks after surgery, the intra-articular graft always failed, not the fixation. Grafts showed bony fixation in the tunnel at 6 weeks and primary healing at the junction of the tunnel and joint after 24 weeks. Tricalcium phosphate was resorbed and simultaneously replaced by bone. Remodeling was still incomplete at 24 weeks. In the sheep model microporous beta-TCP implants used with press-fit fixation of ACL grafts permit early functional rehabilitation. After 6 weeks, the graft is fixed by woven bone or bony integration. Implanted microporous tricalcium phosphate is resorbed and replaced by bone. In a sheep model we showed that primary healing of ACL grafts with resorption and bony replacement of the fixating implant can be achieved by means of press-fit fixation with pure beta-TCP.

Toward beta cell replacement for diabetes

PubMed Central

Johannesson, Bjarki; Sui, Lina; Freytes, Donald O; Creusot, Remi J; Egli, Dieter

2015-01-01

The discovery of insulin more than 90 years ago introduced a life-saving treatment for patients with type 1 diabetes, and since then, significant progress has been made in clinical care for all forms of diabetes. However, no method of insulin delivery matches the ability of the human pancreas to reliably and automatically maintain glucose levels within a tight range. Transplantation of human islets or of an intact pancreas can in principle cure diabetes, but this approach is generally reserved for cases with simultaneous transplantation of a kidney, where immunosuppression is already a requirement. Recent advances in cell reprogramming and beta cell differentiation now allow the generation of personalized stem cells, providing an unlimited source of beta cells for research and for developing autologous cell therapies. In this review, we will discuss the utility of stem cell-derived beta cells to investigate the mechanisms of beta cell failure in diabetes, and the challenges to develop beta cell replacement therapies. These challenges include appropriate quality controls of the cells being used, the ability to generate beta cell grafts of stable cellular composition, and in the case of type 1 diabetes, protecting implanted cells from autoimmune destruction without compromising other aspects of the immune system or the functionality of the graft. Such novel treatments will need to match or exceed the relative safety and efficacy of available care for diabetes. PMID:25733347

Synthetic alleles at position 121 define a functional domain of human interleukin-1 beta.

PubMed

Ambrosetti, D C; Palla, E; Mirtella, A; Galeotti, C; Solito, E; Navarra, P; Parente, L; Melli, M

1996-06-01

The non-conservative substitution of the tyrosine residue at position 121 of human interleukin-1 beta (IL-1 beta) generates protein mutants showing strong reduction of the capacity to induce (a) prostaglandin E2 (PGE2) release from fibroblasts and smooth muscle cells, (b) murine T-cells proliferation and (c) activation of interleukin-6 (IL-6) gene expression. It is generally accepted that these functions are mediated by the type-I interleukin-1 receptor (IL-1RI). However, the mutant proteins maintain the binding affinity to the types-I and II IL-1 receptors, which is the same as the control IL-1 beta, suggesting that this amino acid substitution does not alter the structure of the molecule, except locally. Thus we have identified a new functional site of IL-1 beta different from the known receptor binding region, responsible for fundamental IL-1 beta functions. Moreover, we show that the same mutants maintain at least two hypothalamic functions, that is, the in vitro short-term PGE2 release from rat hypothalamus and the induction of fever in rabbits. This result suggests that there is yet another site of the molecule responsible for the hypothalamic functions, implying that multiple active sites on the IL-1 beta molecule, possibly binding to more than one receptor chain, trigger different signals.

V beta-specific deletion of mature thymocytes induced by the plant superantigen Urtica dioica agglutinin.

PubMed

Delcourt, M; Peumans, W J; Wagner, M C; Truffa-Bachi, P

1996-03-15

Urtica dioica agglutinin (UDA), a plant protein, is a superantigen activating in a MHC class II-restricted manner the V beta 8. 3-bearing T-cells (Galelli and Truffa-Bachi, J. Immunol. 151, 1821, 1993). Administration of UDA to adult mice provokes the clonal expansion of the responding cells which is followed by the deletion of the major fraction of the UDA-sensitive cells, whereas the remaining cells become anergic (Galelli et al., J. Immunol. 154, 2600, 1995). We have analyzed the effect of UDA on thymocytes. Injection of UDA resulted in a rapid, but transient, deletion of a large fraction of the V beta 8.3-bearing mature T-cells. In contrast to other exogenous superantigens, this deletion was not preceded by the clonal expansion of the UDA-responding thymocytes. Moreover, the V beta 8.3-bearing mature T-cells escaping the deletion were not anergic to an in vitro UDA restimulation. UDA and the other superantigens also differ as the general, V beta-unrestricted, thymic atrophy induced by classical superantigens was not observed with UDA.

Modulation of neuroinflammation and pathology in the 5XFAD mouse model of Alzheimer's disease using a biased and selective beta-1 adrenergic receptor partial agonist.

PubMed

Ardestani, Pooneh Memar; Evans, Andrew K; Yi, Bitna; Nguyen, Tiffany; Coutellier, Laurence; Shamloo, Mehrdad

2017-04-01

Degeneration of noradrenergic neurons occurs at an early stage of Alzheimer's Disease (AD). The noradrenergic system regulates arousal and learning and memory, and has been implicated in regulating neuroinflammation. Loss of noradrenergic tone may underlie AD progression at many levels. We have previously shown that acute administration of a partial agonist of the beta-1 adrenergic receptor (ADRB1), xamoterol, restores behavioral deficits in a mouse model of AD. The current studies examined the effects of chronic low dose xamoterol on neuroinflammation, pathology, and behavior in the pathologically aggressive 5XFAD transgenic mouse model of AD. In vitro experiments in cells expressing human beta adrenergic receptors demonstrate that xamoterol is highly selective for ADRB1 and functionally biased for the cAMP over the β-arrestin pathway. Data demonstrate ADRB1-mediated attenuation of TNF-α production with xamoterol in primary rat microglia culture following LPS challenge. Finally, two independent cohorts of 5XFAD and control mice were administered xamoterol from approximately 4.0-6.5 or 7.0-9.5 months, were tested in an array of behavioral tasks, and brains were examined for evidence of neuroinflammation, and amyloid beta and tau pathology. Xamoterol reduced mRNA expression of neuroinflammatory markers (Iba1, CD74, CD14 and TGFβ) and immunohistochemical evidence for microgliosis and astrogliosis. Xamoterol reduced amyloid beta and tau pathology as measured by regional immunohistochemistry. Behavioral deficits were not observed for 5XFAD mice. In conclusion, chronic administration of a selective, functionally biased, partial agonist of ADRB1 is effective in reducing neuroinflammation and amyloid beta and tau pathology in the 5XFAD model of AD. Copyright © 2017 Elsevier Ltd. All rights reserved.

Arsenic-gene interactions and beta-cell function in the Strong Heart Family Study.

PubMed

Balakrishnan, Poojitha; Navas-Acien, Ana; Haack, Karin; Vaidya, Dhananjay; Umans, Jason G; Best, Lyle G; Goessler, Walter; Francesconi, Kevin A; Franceschini, Nora; North, Kari E; Cole, Shelley A; Voruganti, V Saroja; Gribble, Matthew O

2018-06-01

We explored arsenic-gene interactions influencing pancreatic beta-cell activity in the Strong Heart Family Study (SHFS). We considered 42 variants selected for associations with either beta-cell function (31 variants) or arsenic metabolism (11 variants) in the SHFS. Beta-cell function was calculated as homeostatic model - beta corrected for insulin resistance (cHOMA-B) by regressing homeostatic model - insulin resistance (HOMA-IR) on HOMA-B and adding mean HOMA-B. Arsenic exposure was dichotomized at the median of the sum of creatinine-corrected inorganic and organic arsenic species measured by high performance liquid chromatography-inductively coupled plasma mass spectrometry (HPLC-ICPMS). Additive GxE models for cHOMA-B were adjusted for age and ancestry, and accounted for family relationships. Models were stratified by center (Arizona, Oklahoma, North Dakota and South Dakota) and meta-analyzed. The two interactions between higher vs. lower arsenic and SNPs for cHOMA-B that were nominally significant at P < 0.05 were with rs10738708 (SNP overall effect -3.91, P = 0.56; interaction effect with arsenic -31.14, P = 0.02) and rs4607517 (SNP overall effect +16.61, P = 0.03; interaction effect with arsenic +27.02, P = 0.03). The corresponding genes GCK and TUSC1 suggest oxidative stress and apoptosis as possible mechanisms for arsenic impacts on beta-cell function. No interactions were Bonferroni-significant (1.16 × 10 -3 ). Our findings are suggestive of oligogenic moderation of arsenic impacts on pancreatic β-cell endocrine function, but were not Bonferroni-significant. Copyright © 2018 Elsevier Inc. All rights reserved.

Maintained activity of glycogen synthase kinase-3{beta} despite of its phosphorylation at serine-9 in okadaic acid-induced neurodegenerative model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lim, Yong-Whan; Yoon, Seung-Yong, E-mail: ysy@amc.seoul.kr; Institute for Biomacromolecules, University of Ulsan College of Medicine, Seoul

2010-04-30

Glycogen synthase kinase-3{beta} (GSK3{beta}) is recognized as one of major kinases to phosphorylate tau in Alzheimer's disease (AD), thus lots of AD drug discoveries target GSK3{beta}. However, the inactive form of GSK3{beta} which is phosphorylated at serine-9 is increased in AD brains. This is also inconsistent with phosphorylation status of other GSK3{beta} substrates, such as {beta}-catenin and collapsin response mediator protein-2 (CRMP2) since their phosphorylation is all increased in AD brains. Thus, we addressed this paradoxical condition of AD in rat neurons treated with okadaic acid (OA) which inhibits protein phosphatase-2A (PP2A) and induces tau hyperphosphorylation and cell death. Interestingly,more » OA also induces phosphorylation of GSK3{beta} at serine-9 and other substrates including tau, {beta}-catenin and CRMP2 like in AD brains. In this context, we observed that GSK3{beta} inhibitors such as lithium chloride and 6-bromoindirubin-3'-monoxime (6-BIO) reversed those phosphorylation events and protected neurons. These data suggest that GSK3{beta} may still have its kinase activity despite increase of its phosphorylation at serine-9 in AD brains at least in PP2A-compromised conditions and that GSK3{beta} inhibitors could be a valuable drug candidate in AD.« less

A thymosin beta15-like peptide promotes intersegmental myotome extension in the chicken embryo.

PubMed

Chankiewitz, Verena; Morosan-Puopolo, Gabriela; Yusuf, Faisal; Rudloff, Stefan; Pröls, Felicitas; Kleff, Veronika; Hofmann, Dietrich Kurt; Brand-Saberi, Beate

2014-03-01

Beta-thymosins constitute a group of small actin-sequestering peptides. These highly conserved peptides are involved in cytoskeleton dynamics and can influence different cell properties such as motility, substrate adhesion, shape and chemotaxis. As a marker for tumour metastasis, the mammalian thymosin beta15 is believed to have an important diagnostic relevance in cancer prognosis, although little is known about its physiological function. In order to study the role of thymosin beta15(avian) in embryogenesis, we cloned the chicken and quail orthologues of thymosin beta15 and used the chicken as a model for vertebrate development. Avian thymosin beta15, the first known non-mammalian thymosin beta15-like gene, encodes a peptide that possesses a cysteine at position one after the methionine which is a significant difference compared to its mammalian counterparts. Thymosin beta15(avian) expression starts at an early stage of development. The expression pattern changes rapidly with development and differs from that of the related thymosin beta4 gene. The most prominent expression domain is seen in developing muscles of limbs and trunk. Gain-of-function experiments revealed that thymosin beta15(avian) has a function in normal myotome development. Ectopic over-expression of thymosin beta15(avian) leads to premature elongation of myotome cells trespassing segment borders. We conclude that thymosin beta15(avian) has a still undescribed function in promoting myocyte elongation.

Sorption of agrochemical model compounds by sorbent materials containing beta-cyclodextrin.

PubMed

Wilson, Lee D; Mohamed, Mohamed H; Guo, Rui; Pratt, Dawn Y; Kwon, Jae Hyuck; Mahmud, Sarker T

2010-04-01

Polymeric sorbent materials that incorporate beta-cyclodextrin (CD) have been prepared and their sorption behavior toward two model agrochemical contaminant compounds, p-nitrophenol (PNP) and methyl chloride examined. The sorption of PNP was studied in aqueous solution using ultraviolet-visible (UV-Vis) spectroscopy, whereas the sorption of methyl chloride from the gas phase was studied using a Langmuir adsorption method. The sorption results for PNP in solution were compared between granular activated carbon (GAC), modified GAC, CD copolymers, and CD-based mesoporous silica hybrid materials. Nitrogen porosimetry at 77 K was used to estimate the surface area and pore structure properties of the sorbent materials. The sorbents displayed variable surface areas as follows: copolymers (36.2-157 m(2)/g), CD-silica materials (307-906 m(2)/g), surface modified GAC (657 m(2)/g), and granular activated carbon (approximately 10(3) m(2)/g). The sorption capacities for PNP and methyl chloride with the different sorbents are listed in descending order as follows: GAC > copolymers > surface modified GAC > CD-silica hybrid materials. In general, the differences in the sorption properties of the sorbents were related to the following: (i) surface area of the sorbent, (ii) CD content and accessibility, (iii) and the chemical nature of the sorbent material.

Independent Causal Contributions of Alpha- and Beta-Band Oscillations during Movement Selection.

PubMed

Brinkman, Loek; Stolk, Arjen; Marshall, Tom R; Esterer, Sophie; Sharp, Poppy; Dijkerman, H Chris; de Lange, Floris P; Toni, Ivan

2016-08-17

To select a movement, specific neuronal populations controlling particular features of that movement need to be activated, whereas other populations are downregulated. The selective (dis)inhibition of cortical sensorimotor populations is governed by rhythmic neural activity in the alpha (8-12 Hz) and beta (15-25 Hz) frequency range. However, it is unclear whether and how these rhythms contribute independently to motor behavior. Building on a recent dissociation of the sensorimotor alpha- and beta-band rhythms, we test the hypothesis that the beta-band rhythm governs the disinhibition of task-relevant neuronal populations, whereas the alpha-band rhythm suppresses neurons that may interfere with task performance. Cortical alpha- and beta-band rhythms were manipulated with transcranial alternating current stimulation (tACS) while human participants selected how to grasp an object. Stimulation was applied at either 10 or 20 Hz and was imposed on the sensorimotor cortex contralaterally or ipsilaterally to the grasping hand. In line with task-induced changes in endogenous spectral power, the effect of the tACS intervention depended on the frequency and site of stimulation. Whereas tACS stimulation generally increased movement selection times, 10 Hz stimulation led to relatively faster selection times when applied to the hemisphere ipsilateral to the grasping hand, compared with other stimulation conditions. These effects occurred selectively when multiple movements were considered. These observations functionally differentiate the causal contribution of alpha- and beta-band oscillations to movement selection. The findings suggest that sensorimotor beta-band rhythms disinhibit task-relevant populations, whereas alpha-band rhythms inhibit neuronal populations that could interfere with movement selection. This study shows dissociable effects of 10 Hz and 20 Hz tACS on the duration of movement selection. These observations have two elements of general relevance. First, the finding that alpha- and beta-band oscillations contribute independently to movement selection provides insight in how oscillations orchestrate motor behavior, which is key to understand movement selection deficits in neurodegenerative disorders. Second, the findings highlight the potential of 10 Hz stimulation as a neurophysiologically grounded intervention to enhance human performance. In particular, this intervention can potentially be exploited to boost rehabilitation after neural damage by targeting the unaffected hemisphere. Copyright © 2016 Brinkman et al.

Hypertrophic stimulation increases beta-actin dynamics in adult feline cardiomyocytes.

PubMed

Balasubramanian, Sundaravadivel; Mani, Santhosh K; Kasiganesan, Harinath; Baicu, Catalin C; Kuppuswamy, Dhandapani

2010-07-12

The myocardium responds to hemodynamic stress through cellular growth and organ hypertrophy. The impact of cytoskeletal elements on this process, however, is not fully understood. While alpha-actin in cardiomyocytes governs muscle contraction in combination with the myosin motor, the exact role of beta-actin has not been established. We hypothesized that in adult cardiomyocytes, as in non-myocytes, beta-actin can facilitate cytoskeletal rearrangement within cytoskeletal structures such as Z-discs. Using a feline right ventricular pressure overload (RVPO) model, we measured the level and distribution of beta-actin in normal and pressure overloaded myocardium. Resulting data demonstrated enriched levels of beta-actin and enhanced translocation to the Triton-insoluble cytoskeletal and membrane skeletal complexes. In addition, RVPO in vivo and in vitro hypertrophic stimulation with endothelin (ET) or insulin in isolated adult cardiomyocytes enhanced the content of polymerized fraction (F-actin) of beta-actin. To determine the localization and dynamics of beta-actin, we adenovirally expressed GFP-tagged beta-actin in isolated adult cardiomyocytes. The ectopically expressed beta-actin-GFP localized to the Z-discs, costameres, and cell termini. Fluorescence recovery after photobleaching (FRAP) measurements of beta-actin dynamics revealed that beta-actin at the Z-discs is constantly being exchanged with beta-actin from cytoplasmic pools and that this exchange is faster upon hypertrophic stimulation with ET or insulin. In addition, in electrically stimulated isolated adult cardiomyocytes, while beta-actin overexpression improved cardiomyocyte contractility, immunoneutralization of beta-actin resulted in a reduced contractility suggesting that beta-actin could be important for the contractile function of adult cardiomyocytes. These studies demonstrate the presence and dynamics of beta-actin in the adult cardiomyocyte and reinforce its usefulness in measuring cardiac cytoskeletal rearrangement during hypertrophic stimulation.

Length dependence of electron transport through molecular wires--a first principles perspective.

PubMed

Khoo, Khoong Hong; Chen, Yifeng; Li, Suchun; Quek, Su Ying

2015-01-07

One-dimensional wires constitute a fundamental building block in nanoscale electronics. However, truly one-dimensional metallic wires do not exist due to Peierls distortion. Molecular wires come close to being stable one-dimensional wires, but are typically semiconductors, with charge transport occurring via tunneling or thermally-activated hopping. In this review, we discuss electron transport through molecular wires, from a theoretical, quantum mechanical perspective based on first principles. We focus specifically on the off-resonant tunneling regime, applicable to shorter molecular wires (<∼4-5 nm) where quantum mechanics dictates electron transport. Here, conductance decays exponentially with the wire length, with an exponential decay constant, beta, that is independent of temperature. Different levels of first principles theory are discussed, starting with the computational workhorse - density functional theory (DFT), and moving on to many-electron GW methods as well as GW-inspired DFT + Sigma calculations. These different levels of theory are applied in two major computational frameworks - complex band structure (CBS) calculations to estimate the tunneling decay constant, beta, and Landauer-Buttiker transport calculations that consider explicitly the effects of contact geometry, and compute the transmission spectra directly. In general, for the same level of theory, the Landauer-Buttiker calculations give more quantitative values of beta than the CBS calculations. However, the CBS calculations have a long history and are particularly useful for quick estimates of beta. Comparing different levels of theory, it is clear that GW and DFT + Sigma calculations give significantly improved agreement with experiment compared to DFT, especially for the conductance values. Quantitative agreement can also be obtained for the Seebeck coefficient - another independent probe of electron transport. This excellent agreement provides confirmative evidence of off-resonant tunneling in the systems under investigation. Calculations show that the tunneling decay constant beta is a robust quantity that does not depend on details of the contact geometry, provided that the same contact geometry is used for all molecular lengths considered. However, because conductance is sensitive to contact geometry, values of beta obtained by considering conductance values where the contact geometry is changing with the molecular junction length can be quite different. Experimentally measured values of beta in general compare well with beta obtained using DFT + Sigma and GW transport calculations, while discrepancies can be attributed to changes in the experimental contact geometries with molecular length. This review also summarizes experimental and theoretical efforts towards finding perfect molecular wires with high conductance and small beta values.

Anesthetic effects in Alzheimer transgenic mouse models.

PubMed

Tang, Junxia X; Eckenhoff, Maryellen F

2013-12-02

Research has improved the diagnosis of Alzheimer's disease, and at earlier stages, but effective therapy continues to be elusive. Current effort is focused on delay. Environmental factors are thought to interact with genetics to modulate the progression of the disease, and one such environmental factor is exposure to general anesthetics. The possibility that some anesthetic effects have long-term consequences is of general interest and concern. The difficulty of studying a chronic, age-related disease in humans combined with the fact that anesthetics are rarely given without surgery, has led to a focus on animal models. Transgenic mouse models have been developed to mimic the hallmarks of Alzheimer's disease, including amyloid beta accumulation (plaque), neurofibrillary tangles, and cognitive dysfunction. While none of the models recapitulate the human disease with high fidelity, they allow a first look at anesthetic-Alzheimer interactions in a reasonable time frame. In studies found to date, none have concluded that anesthetics alone cause a significant change in cognitive decline, but rather an acceleration in Alzheimer neuropathology. Further studies are required to define the best anesthetic paradigm for our elderly population to mitigate changes in neuropathology and potentially cognition. Copyright © 2012 Elsevier Inc. All rights reserved.

A mapping closure for turbulent scalar mixing using a time-evolving reference field

NASA Technical Reports Server (NTRS)

Girimaji, Sharath S.

1992-01-01

A general mapping-closure approach for modeling scalar mixing in homogeneous turbulence is developed. This approach is different from the previous methods in that the reference field also evolves according to the same equations as the physical scalar field. The use of a time-evolving Gaussian reference field results in a model that is similar to the mapping closure model of Pope (1991), which is based on the methodology of Chen et al. (1989). Both models yield identical relationships between the scalar variance and higher-order moments, which are in good agreement with heat conduction simulation data and can be consistent with any type of epsilon(phi) evolution. The present methodology can be extended to any reference field whose behavior is known. The possibility of a beta-pdf reference field is explored. The shortcomings of the mapping closure methods are discussed, and the limit at which the mapping becomes invalid is identified.

On the covariant gauge {alpha} of the linearized gravity in de Sitter spacetime

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cheong, Lee Yen

2012-09-26

In previous work, we studied the linearized gravity with covariant gauge {beta}= 2/3 and {alpha}= 5/3. It was found that the sum of the source and initial contributions reproduces the correct field configuration over the whole de Sitter spacetime. In this paper, we extend this work to generalizing the linearized gravitational field in an arbitrary value of the gauge parameter {alpha} but the gauge parameter {beta} remains the same.

Electroencephalography as a Tool for Assessment of Brain Ischemic Alterations after Open Heart Operations

PubMed Central

Golukhova, Elena Z.; Polunina, Anna G.; Lefterova, Natalia P.; Begachev, Alexey V.

2011-01-01

Cardiac surgery is commonly associated with brain ischemia. Few studies addressed brain electric activity changes after on-pump operations. Eyes closed EEG was performed in 22 patients (mean age: 45.2 ± 11.2) before and two weeks after valve replacement. Spouses of patients were invited to participate as controls. Generalized increase of beta power most prominent in beta-1 band was an unambiguous pathological sign of postoperative cortex dysfunction, probably, manifesting due to gamma-activity slowing (“beta buzz” symptom). Generalized postoperative increase of delta-1 mean frequency along with increase of slow-wave activity in right posterior region may be hypothesized to be a consequence of intraoperative ischemia as well. At the same time, significant changes of alpha activity were observed in both patient and control groups, and, therefore, may be considered as physiological. Unexpectedly, controls showed prominent increase of electric activity in left temporal region whereas patients were deficient in left hemisphere activity in comparison with controls at postoperative followup. Further research is needed in order to determine the true neurological meaning of the EEG findings after on-pump operations. PMID:21776370

Mechanism of the hydrolysis of 4-methylumbelliferyl-beta-D-glucoside by germinating and outgrowing spores of Bacillus species.

PubMed

Setlow, B; Cabrera-Martinez, R-M; Setlow, P

2004-01-01

To determine the mechanism of the hydrolysis of 4-methylumbelliferyl-beta-D-glucopyranoside (beta-MUG) by germinating and outgrowing spores of Bacillus species. Spores of B. atrophaeus (formerly B. subtilis var. niger, Fritze and Pukall 2001) are used as biological indicators of the efficacy of ethylene oxide sterilization by measurement of beta-MUG hydrolysis during spore germination and outgrowth. It was previously shown that beta-MUG is hydrolysed to 4-methylumbelliferone (MU) during the germination and outgrowth of B. atrophaeus spores (Chandrapati and Woodson 2003), and this was also the case with spores of B. subtilis 168. Germination of spores of either B. atrophaeus or B. subtilis with chloramphenicol reduced beta-MUG hydrolysis by almost 99%, indicating that proteins needed for rapid beta-MUG hydrolysis are synthesized during spore outgrowth. However, the residual beta-MUG hydrolysis during spore germination with chloramphenicol indicated that dormant spores contain low levels of proteins needed for beta-MUG uptake and hydrolysis. With B. subtilis 168 spores that lacked several general proteins of the phosphotransferase system (PTS) for sugar uptake, beta-MUG hydrolysis during spore germination and outgrowth was decreased >99.9%. This indicated that beta-MUG is taken up by the PTS, resulting in the intracellular accumulation of the phosphorylated form of beta-MUG, beta-MUG-6-phosphate (beta-MUG-P). This was further demonstrated by the lack of detectable glucosidase activity on beta-MUG in dormant, germinated and outgrowing spore extracts, while phosphoglucosidase active on beta-MUG-P was readily detected. Dormant B. subtilis 168 spores had low levels of at least four phosphoglucosidases active on beta-MUG-P: BglA, BglH, BglC (originally called YckE) and BglD (originally called YdhP). These enzymes were also detected in spores germinating and outgrowing with beta-MUG, but levels of BglH were the highest, as this enzyme's synthesis was induced ca 100-fold during spore outgrowth in the presence of beta-MUG. Deletion of the genes coding for BglA, BglH, BglC and BglD reduced beta-MUG hydrolysis by germinating and outgrowing spores of B. subtilis 168 at least 99.7%. Assay of glucosidases active on beta-MUG or beta-MUG-P in extracts of dormant and outgrowing spores of B. atrophaeus revealed no enzyme active on beta-MUG and one enzyme that comprised > or =90% of the phosphoglucosidase active on beta-MUG-P. Partial purification and amino-terminal sequence analysis of this phosphoglucosidase identified this enzyme as BglH. Generation of MU from beta-MUG by germinating and outgrowing spores of B. atrophaeus and B. subtilis is mediated by the PTS-driven uptake and phosphorylation of beta-MUG, followed by phosphoglucosidase action on the intracellular beta-MUG-P. The major phosphoglucosidase catalyzing MU generation from beta-MUG-P in spores of both species is probably BglH. This work provides new insight into the mechanism of uptake and hydrolysis of beta-MUG by germinating and outgrowing spores of Bacillus species, in particular B. atrophaeus. The research reported here provides a biological basis for a Rapid Readout Biological Indicator that is used to monitor the efficacy of ethylene oxide sterilization.

A cross-linking study of the Ca2+, Mg2+-activated adenosine triphosphatase of Escherichia coli.

PubMed

Bragg, P D; Hou, C

1980-05-01

The solubilized Ca2+,Mg2+-activated adenosine triphosphatase of Escherichia coli is composed of five subunits designated alpha, beta, gamma, delta and epsilon in order of decreasing molecular weight. The subunit structure of the enzyme has been investigated by the use of the cleavable cross-linking agents dithiobis(succinimidyl propionate), methyl-4-mercaptobutyrimidate, dimethyl-3,3'-dithiobispropionimidate, disuccinimidyl tartarate, and cupric 1,10-phenanthrolinate. The products of cross-linking were analyzed by two different two-dimensional gel electrophoresis systems. The following cross-linked subunit dimers were observed: alpha 2, beta 2, alpha beta, alpha delta, beta gamma, beta delta, beta epsilon and gamma epsilon. These results, together with other published data, are discussed in relation to a model of the arrangement of the subunits in the ATPase molecule.

Time-dependent fiber bundles with local load sharing. II. General Weibull fibers.

PubMed

Phoenix, S Leigh; Newman, William I

2009-12-01

Fiber bundle models (FBMs) are useful tools in understanding failure processes in a variety of material systems. While the fibers and load sharing assumptions are easily described, FBM analysis is typically difficult. Monte Carlo methods are also hampered by the severe computational demands of large bundle sizes, which overwhelm just as behavior relevant to real materials starts to emerge. For large size scales, interest continues in idealized FBMs that assume either equal load sharing (ELS) or local load sharing (LLS) among fibers, rules that reflect features of real load redistribution in elastic lattices. The present work focuses on a one-dimensional bundle of N fibers under LLS where life consumption in a fiber follows a power law in its load, with exponent rho , and integrated over time. This life consumption function is further embodied in a functional form resulting in a Weibull distribution for lifetime under constant fiber stress and with Weibull exponent, beta. Thus the failure rate of a fiber depends on its past load history, except for beta=1 . We develop asymptotic results validated by Monte Carlo simulation using a computational algorithm developed in our previous work [Phys. Rev. E 63, 021507 (2001)] that greatly increases the size, N , of treatable bundles (e.g., 10(6) fibers in 10(3) realizations). In particular, our algorithm is O(N ln N) in contrast with former algorithms which were O(N2) making this investigation possible. Regimes are found for (beta,rho) pairs that yield contrasting behavior for large N. For rho>1 and large N, brittle weakest volume behavior emerges in terms of characteristic elements (groupings of fibers) derived from critical cluster formation, and the lifetime eventually goes to zero as N-->infinity , unlike ELS, which yields a finite limiting mean. For 1/21 but with 0

Practice advisory: The utility of EEG theta/beta power ratio in ADHD diagnosis

PubMed Central

Gloss, David; Varma, Jay K.; Pringsheim, Tamara; Nuwer, Marc R.

2016-01-01

Objective: To evaluate the evidence for EEG theta/beta power ratio for diagnosing, or helping to diagnose, attention-deficit/hyperactivity disorder (ADHD). Methods: We identified relevant studies and classified them using American Academy of Neurology criteria. Results: Two Class I studies assessing the ability of EEG theta/beta power ratio and EEG frontal beta power to identify patients with ADHD correctly identified 166 of 185 participants. Both studies evaluated theta/beta power ratio and frontal beta power in suspected ADHD or in syndromes typically included in an ADHD differential diagnosis. A bivariate model combining the diagnostic studies shows that the combination of EEG frontal beta power and theta/beta power ratio has relatively high sensitivity and specificity but is insufficiently accurate. Conclusions: It is unknown whether a combination of standard clinical examination and EEG theta/beta power ratio increases diagnostic certainty of ADHD compared with clinical examination alone. Recommendations: Level B: Clinicians should inform patients with suspected ADHD and their families that the combination of EEG theta/beta power ratio and frontal beta power should not replace a standard clinical evaluation. There is a risk for significant harm to patients from ADHD misdiagnosis because of the unacceptably high false-positive diagnostic rate of EEG theta/beta power ratio and frontal beta power. Level R: Clinicians should inform patients with suspected ADHD and their families that the EEG theta/beta power ratio should not be used to confirm an ADHD diagnosis or to support further testing after a clinical evaluation, unless such diagnostic assessments occur in a research setting. PMID:27760867

Synthesis and structure-activity relationships of imidazo[1,2-a]pyrimidin-5(1H)-ones as a novel series of beta isoform selective phosphatidylinositol 3-kinase inhibitors.

PubMed

Lin, Hong; Erhard, Karl; Hardwicke, Mary Ann; Luengo, Juan I; Mack, James F; McSurdy-Freed, Jeanelle; Plant, Ramona; Raha, Kaushik; Rominger, Cynthia M; Sanchez, Robert M; Schaber, Michael D; Schulz, Mark J; Spengler, Michael D; Tedesco, Rosanna; Xie, Ren; Zeng, Jin J; Rivero, Ralph A

2012-03-15

A series of PI3K-beta selective inhibitors, imidazo[1,2-a]-pyrimidin-5(1H)-ones, has been rationally designed based on the docking model of the more potent R enantiomer of TGX-221, identified by a chiral separation, in a PI3K-beta homology model. Synthesis and SAR of this novel chemotype are described. Several compounds in the series demonstrated potent growth inhibition in a PTEN-deficient breast cancer cell line MDA-MB-468 under anchorage independent conditions. Copyright © 2012 Elsevier Ltd. All rights reserved.

Anomalous Transport in High Beta Poloidal DIII-D Discharges

NASA Astrophysics Data System (ADS)

Pankin, A.; Garofalo, A.; Kritz, A.; Rafiq, T.; Weiland, J.

2016-10-01

Dominant instabilities that drive anomalous transport in high beta poloidal DIII-D discharges are investigated using the MMM7.1, and TGLF models in the predictive integrated modeling TRANSP code. The ion thermal transport is found to be strongly reduced in these discharges, but turbulence driven by the ITG modes along with the neoclassical transport still play a role in determining the ion temperature profiles. The electron thermal transport driven by the ETG modes impact the electron temperature profiles. The E × B flow shear is found to have a small effect in reducing the electron thermal transport. The Shafranov shift is found to strongly reduce the anomalous transport in the high beta poloidal DIII-D discharges. The reduction of Shafranov shift can destroy the ion internal transport barrier and can result in significantly lower core temperatures. The MMM7.1 model predicts electron and ion temperature profiles reasonably well, but it fails to accurately predict the properties of electron internal transport barrier, which indicates that the ETG model in MMM7.1 needs to be improved in the high beta poloidal operational regime. Research supported by the Office of Science, US DOE.

Degradation of lycopene and beta-carotene in model systems and in lyophilized guava during ambient storage: kinetics, structure, and matrix effects.

PubMed

Ferreira, J E M; Rodriguez-Amaya, D B

2008-10-01

Being highly unsaturated, carotenoids are susceptible to isomerization and oxidation during the processing and storage of food. In the present study, the degradation of acyclic lycopene and dicyclic beta-carotene in low-moisture and aqueous model systems, as well as in lyophilized guava, during storage at ambient temperature, in the absence or presence of light, was investigated. Both carotenoids followed first order kinetics under the various conditions investigated. Lycopene degraded much faster than beta-carotene in all the model systems. In a comparison of lycopene isolated from guava, tomato, and watermelon, greater losses were observed with lycopene from tomato. Since the model system was identical in the 3 cases, these results indicated that other compounds from the food sources, co-extracted with lycopene, might have influenced the oxidation. Light consistently and strongly promoted degradation under all conditions studied. The susceptibility of lycopene to degradation was much less in lyophilized guava than in the model systems, showing the marked protective influence of the food matrix. Loss of beta-carotene, found at a concentration of about 18 times lower than lycopene, was only slightly lower than that of lycopene in lyophilized guava, indicating that the effect of matrix and/or the initial concentration overshadowed the structural influence.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Adams, J.U.; Andrews, J.S.; Hiller, J.M.

This study was essentially an in vivo protection experiment designed to test further the hypothesis that stress induces release of endogenous opiods which then act at opioid receptors. Rats that were either subjected to restraint stress for 1 yr or unstressed were injected ICV with either saline or 2.5 ..mu..g of ..beta..-funaltrexamine (..beta..-FNA), an irreversible opioid antagonist that alkylates the mu-opioid receptor. Twenty-four hours later, subjects were tested unstressed for morphine analgesia or were sacrificed and opioid binding in brain was determined. (/sup 3/H)D-Ala/sup 2/NMePhe/sup 4/-Gly/sup 5/(ol)enkephalin (DAGO) served as a specific ligand for mu-opioid receptors, and (/sup 3/H)-bremazocine asmore » a general ligand for all opioid receptors. Rats injected with saline while stressed were significantly less sensitive to the analgesic action of morphine 24 hr later than were their unstressed counterparts. ..beta..-FNA pretreatment attenuated morphine analgesia in an insurmountable manner. Animals pretreated with ..beta..-FNA while stressed were significantly more sensitive to the analgesic effect of morphine than were animals that received ..beta..-FNA while unstressed. ..beta..-FNA caused small and similar decreases in (/sup 3/H)-DAGO binding in brain of both stressed and unstressed animals. 35 references, 2 figures, 2 tables.« less

Analysis and expression of the alpha-expansin and beta-expansin gene families in maize

NASA Technical Reports Server (NTRS)

Wu, Y.; Meeley, R. B.; Cosgrove, D. J.

2001-01-01

Expansins comprise a multigene family of proteins in maize (Zea mays). We isolated and characterized 13 different maize expansin cDNAs, five of which are alpha-expansins and eight of which are beta-expansins. This paper presents an analysis of these 13 expansins, as well as an expression analysis by northern blotting with materials from young and mature maize plants. Some expansins were expressed in restricted regions, such as the beta-expansins ExpB1 (specifically expressed in maize pollen) and ExpB4 (expressed principally in young husks). Other expansins such as alpha-expansin Exp1 and beta-expansin ExpB2 were expressed in several organs. The expression of yet a third group was not detected in the selected organs and tissues. An analysis of expansin sequences from the maize expressed sequence tag collection is also presented. Our results indicate that expansin genes may have general, overlapping expression in some instances, whereas in other cases the expression may be highly specific and limited to a single organ or cell type. In contrast to the situation in Arabidopsis, beta-expansins in maize seem to be more numerous and more highly expressed than are alpha-expansins. The results support the concept that beta-expansins multiplied and evolved special functions in the grasses.

Determination of the volume activity concentration of alpha artificial radionuclides with alpha spectrometer.

PubMed

Liu, B; Zhang, Q; Li, Y

1997-12-01

This paper introduces a method to determine the volume activity concentration of alpha and/or beta artificial radionuclides in the environment and radon/thoron progeny background-compensation based on a Si surface-barrier detector. By measuring the alpha peak counts of 218Po and 214Po in two time intervals, the activity concentration of 218Po, 214Pb and 214Bi aerosol particles were determined; meanwhile, the total beta count of 214Pb and 214Bi aerosols was also calculated from their decay scheme. With the average equilibrium factor of thoron progeny in general environment, the alpha and beta counts of thoron progeny were approximately evaluated by 212Po alpha peak counts. The alpha count of transuranic aerosols was determined by subtracting the trail counts of radon/thoron progeny alpha peaks. The total count of beta artificial radionuclides was determined by subtracting the beta counts of radon/thoron progeny aerosol particles. In our preliminary experiments, if the radon progeny concentration is less than 15 Bq m(-3), the lower limit of detection of transuranics concentration is less than 0.1 Bq m(-3). Even if the radon progeny concentration is as high as 75 Bq m(-3), the lower limit of detection of total beta activity concentration of artificial nuclides aerosols is less than 1 Bq m(-3).

Evaluating mepindolol in a test model of examination anxiety in students.

PubMed

Krope, P; Kohrs, A; Ott, H; Wagner, W; Fichte, K

1982-03-01

The effect of a single dose of beta-blocker (5 or 10 mg mepindolol) during a written examination was investigated in two double-blind studies (N : 49 and 55 students, respectively). The question was whether the beta-blocker would in comparison to placebo diminish examination anxiety and improve the performance of highly complex tasks, while leaving the performance of less complex tasks unchanged. A reduction in examination anxiety after beta-blocker intake could not be demonstrated with a multi-level test model (which included the parameters self-rated anxiety, motor behaviour, task performance and physiology), although pulse rates were lowered significantly. An improvement in performance could not be observed, while - by the same token - the performance was not impaired by the beta-blocker. A hypothesis according to which a beta-blocker has an anxiolytic effect and improves performance, dependent on the level of habitual examination anxiety, was tested post hoc, but could not be confirmed. Ten of the subjects treated with 10 mg mepindolol, complained of different side effects, including dizziness, fatigue and headache.

Modeling the mechanism of CLN025 beta-hairpin formation

NASA Astrophysics Data System (ADS)

McKiernan, Keri A.; Husic, Brooke E.; Pande, Vijay S.

2017-09-01

Beta-hairpins are substructures found in proteins that can lend insight into more complex systems. Furthermore, the folding of beta-hairpins is a valuable test case for benchmarking experimental and theoretical methods. Here, we simulate the folding of CLN025, a miniprotein with a beta-hairpin structure, at its experimental melting temperature using a range of state-of-the-art protein force fields. We construct Markov state models in order to examine the thermodynamics, kinetics, mechanism, and rate-determining step of folding. Mechanistically, we find the folding process is rate-limited by the formation of the turn region hydrogen bonds, which occurs following the downhill hydrophobic collapse of the extended denatured protein. These results are presented in the context of established and contradictory theories of the beta-hairpin folding process. Furthermore, our analysis suggests that the AMBER-FB15 force field, at this temperature, best describes the characteristics of the full experimental CLN025 conformational ensemble, while the AMBER ff99SB-ILDN and CHARMM22* force fields display a tendency to overstabilize the native state.

Predicting Successful Treatment Outcome of Web-Based Self-help for Problem Drinkers: Secondary Analysis From a Randomized Controlled Trial

PubMed Central

Kramer, Jeannet; Keuken, Max; Smit, Filip; Schippers, Gerard; Cuijpers, Pim

2008-01-01

Background Web-based self-help interventions for problem drinking are coming of age. They have shown promising results in terms of cost-effectiveness, and they offer opportunities to reach out on a broad scale to problem drinkers. The question now is whether certain groups of problem drinkers benefit more from such Web-based interventions than others. Objective We sought to identify baseline, client-related predictors of the effectiveness of Drinking Less, a 24/7, free-access, interactive, Web-based self-help intervention without therapist guidance for problem drinkers who want to reduce their alcohol consumption. The intervention is based on cognitive-behavioral and self-control principles. Methods We conducted secondary analysis of data from a pragmatic randomized trial with follow-up at 6 and 12 months. Participants (N = 261) were adult problem drinkers in the Dutch general population with a weekly alcohol consumption above 210 g of ethanol for men or 140 g for women, or consumption of at least 60 g (men) or 40 g (women) one or more days a week over the past 3 months. Six baseline participant characteristics were designated as putative predictors of treatment response: (1) gender, (2) education, (3) Internet use competence (sociodemographics), (4) mean weekly alcohol consumption, (5) prior professional help for alcohol problems (level of problem drinking), and (6) participants’ expectancies of Web-based interventions for problem drinking. Intention-to-treat (ITT) analyses, using last-observation-carried-forward (LOCF) data, and regression imputation (RI) were performed to deal with loss to follow-up. Statistical tests for interaction terms were conducted and linear regression analysis was performed to investigate whether the participants’ characteristics as measured at baseline predicted positive treatment responses at 6- and 12-month follow-ups. Results At 6 months, prior help for alcohol problems predicted a small, marginally significant positive treatment outcome in the RI model only (beta = .18, P = .05, R2 = .11). At 12 months, females displayed modest predictive power in both imputation models (LOCF: beta = .22, P = .045, R2 = .02; regression: beta = .27, P = .01, R2 = .03). Those with higher levels of education exhibited modest predictive power in the LOCF model only (beta = .33, P = .01, R2 = .03). Conclusions Although female and more highly educated users appeared slightly more likely to derive benefit from the Drinking Less intervention, none of the baseline characteristics we studied persuasively predicted a favorable treatment outcome. The Web-based intervention therefore seems well suited for a heterogeneous group of problem drinkers and could hence be offered as a first-step treatment in a stepped-care approach directed at problem drinkers in the general population. Trial Registration International Standard Randomized Controlled Trial Number (ISRCTN): 47285230; http://www.controlled-trials.com/isrctn47285230 (Archived by WebCite at http://www.webcitation.org/5cSR2sMkp). PMID:19033150

Predicting successful treatment outcome of web-based self-help for problem drinkers: secondary analysis from a randomized controlled trial.

PubMed

Riper, Heleen; Kramer, Jeannet; Keuken, Max; Smit, Filip; Schippers, Gerard; Cuijpers, Pim

2008-11-22

Web-based self-help interventions for problem drinking are coming of age. They have shown promising results in terms of cost-effectiveness, and they offer opportunities to reach out on a broad scale to problem drinkers. The question now is whether certain groups of problem drinkers benefit more from such Web-based interventions than others. We sought to identify baseline, client-related predictors of the effectiveness of Drinking Less, a 24/7, free-access, interactive, Web-based self-help intervention without therapist guidance for problem drinkers who want to reduce their alcohol consumption. The intervention is based on cognitive-behavioral and self-control principles. We conducted secondary analysis of data from a pragmatic randomized trial with follow-up at 6 and 12 months. Participants (N = 261) were adult problem drinkers in the Dutch general population with a weekly alcohol consumption above 210 g of ethanol for men or 140 g for women, or consumption of at least 60 g (men) or 40 g (women) one or more days a week over the past 3 months. Six baseline participant characteristics were designated as putative predictors of treatment response: (1) gender, (2) education, (3) Internet use competence (sociodemographics), (4) mean weekly alcohol consumption, (5) prior professional help for alcohol problems (level of problem drinking), and (6) participants' expectancies of Web-based interventions for problem drinking. Intention-to-treat (ITT) analyses, using last-observation-carried-forward (LOCF) data, and regression imputation (RI) were performed to deal with loss to follow-up. Statistical tests for interaction terms were conducted and linear regression analysis was performed to investigate whether the participants' characteristics as measured at baseline predicted positive treatment responses at 6- and 12-month follow-ups. At 6 months, prior help for alcohol problems predicted a small, marginally significant positive treatment outcome in the RI model only (beta = .18, P = .05, R(2) = .11). At 12 months, females displayed modest predictive power in both imputation models (LOCF: beta = .22, P = .045, R(2) = .02; regression: beta = .27, P = .01, R(2) = .03). Those with higher levels of education exhibited modest predictive power in the LOCF model only (beta = .33, P = .01, R(2) = .03). Although female and more highly educated users appeared slightly more likely to derive benefit from the Drinking Less intervention, none of the baseline characteristics we studied persuasively predicted a favorable treatment outcome. The Web-based intervention therefore seems well suited for a heterogeneous group of problem drinkers and could hence be offered as a first-step treatment in a stepped-care approach directed at problem drinkers in the general population. International Standard Randomized Controlled Trial Number (ISRCTN): 47285230; http://www.controlled-trials.com/isrctn47285230 (Archived by WebCite at http://www.webcitation.org/5cSR2sMkp).

Inhibition of beta-adrenergic receptor trafficking in adult cardiocytes by MAP4 decoration of microtubules.

PubMed

Cheng, Guangmao; Qiao, Fei; Gallien, Thomas N; Kuppuswamy, Dhandapani; Cooper, George

2005-03-01

Decreased beta-adrenergic receptor (beta-AR) number occurs both in animal models of cardiac hypertrophy and failure and in patients. beta-AR recycling is an important mechanism for the beta-AR resensitization that maintains a normal complement of cell surface beta-ARs. We have shown that 1) in severe pressure overload cardiac hypertrophy, there is extensive microtubule-associated protein 4 (MAP4) decoration of a dense microtubule network; and 2) MAP4 microtubule decoration inhibits muscarinic acetylcholine receptor recycling in neuroblastoma cells. We asked here whether MAP4 microtubule decoration inhibits beta-AR recycling in adult cardiocytes. [(3)H]CGP-12177 was used as a beta-AR ligand, and feline cardiocytes were isolated and infected with adenovirus containing MAP4 (AdMAP4) or beta-galactosidase (Adbeta-gal) cDNA. MAP4 decorated the microtubules extensively only in AdMAP4 cardiocytes. beta-AR agonist exposure reduced cell surface beta-AR number comparably in AdMAP4 and Adbeta-gal cardiocytes; however, after agonist withdrawal, the cell surface beta-AR number recovered to 78.4 +/- 2.9% of the pretreatment value in Adbeta-gal cardiocytes but only to 56.8 +/- 1.4% in AdMAP4 cardiocytes (P < 0.01). This result was confirmed in cardiocytes isolated from transgenic mice having cardiac-restricted MAP4 overexpression. In functional terms of cAMP generation, beta-AR agonist responsiveness of AdMAP4 cells was 47% less than that of Adbeta-gal cells. We conclude that MAP4 microtubule decoration interferes with beta-AR recycling and that this may be one mechanism for beta-AR downregulation in heart failure.

Direct ethanol production from barley beta-glucan by sake yeast displaying Aspergillus oryzae beta-glucosidase and endoglucanase.

PubMed

Kotaka, Atsushi; Bando, Hiroki; Kaya, Masahiko; Kato-Murai, Michiko; Kuroda, Kouichi; Sahara, Hiroshi; Hata, Yoji; Kondo, Akihiko; Ueda, Mitsuyoshi

2008-06-01

Three beta-glucosidase- and two endoglucanase-encoding genes were cloned from Aspergillus oryzae, and their gene products were displayed on the cell surface of the sake yeast, Saccharomyces cerevisiae GRI-117-UK. GRI-117-UK/pUDB7 displaying beta-glucosidase AO090009000356 showed the highest activity against various substrates and efficiently produced ethanol from cellobiose. On the other hand, GRI-117-UK/pUDCB displaying endoglucanase AO090010000314 efficiently degraded barley beta-glucan to glucose and smaller cellooligosaccharides. GRI-117-UK/pUDB7CB codisplaying both beta-glucosidase AO090009000356 and endoglucanase AO090010000314 was constructed. When direct ethanol fermentation from 20 g/l barley beta-glucan as a model substrate was performed with the codisplaying strain, the ethanol concentration reached 7.94 g/l after 24 h of fermentation. The conversion ratio of ethanol from beta-glucan was 69.6% of the theoretical ethanol concentration produced from 20 g/l barley beta-glucan. These results showed that sake yeast displaying A. oryzae cellulolytic enzymes can be used to produce ethanol from cellulosic materials. Our constructs have higher ethanol production potential than the laboratory constructs previously reported.

Stress, anxiety, depression, and epilepsy: investigating the relationship between psychological factors and seizures.

PubMed

Thapar, Ajay; Kerr, Michael; Harold, Gordon

2009-01-01

The goal of the study described here was to examine the interrelationship between psychological factors (anxiety, stress, and depression) and seizures. In this longitudinal cohort study, data on anxiety, depression, perceived stress, and seizure recency (time since last seizure) and frequency were collected at two time points using standard validated questionnaire measures. Empirically based models with psychological factors explaining change in (1) seizure recency and (2) seizure frequency scores across time were specified. We then tested how these psychological factors acted together in predicting seizure recency and frequency. Our data were used to test whether these models were valid for the study population. Latent variable structural equation modeling was used for the analysis. Four hundred thirty-three of the 558 individuals who initially consented to participate provided two waves of data for this analysis. Stress (beta=0.25, P<0.01), anxiety (beta=0.30, P<0.01), and depression (beta=0.30, P<0.01) all predicted change in seizure recency. However, it was depression that mediated the relationship of both anxiety and stress with modeled change in seizure recency (beta=0.19, P<0.01) and seizure frequency (beta=0.30, P<0.01) over time. Depression mediates the relationship between stress and anxiety and change in seizure recency and seizure frequency. These findings highlight the importance of depression management in addition to seizure management in the assessment and treatment of epilepsy in an adult population.

Beta-adrenergic signaling promotes tumor angiogenesis and prostate cancer progression through HDAC2-mediated suppression of thrombospondin-1.

PubMed

Hulsurkar, M; Li, Z; Zhang, Y; Li, X; Zheng, D; Li, W

2017-03-01

Chronic behavioral stress and beta-adrenergic signaling have been shown to promote cancer progression, whose underlying mechanisms are largely unclear, especially the involvement of epigenetic regulation. Histone deacetylase-2 (HDAC2), an epigenetic regulator, is critical for stress-induced cardiac hypertrophy. It is unknown whether it is necessary for beta-adrenergic signaling-promoted cancer progression. Using xenograft models, we showed that chronic behavioral stress and beta-adrenergic signaling promote angiogenesis and prostate cancer progression. HDAC2 was induced by beta-adrenergic signaling in vitro and in mouse xenografts. We next uncovered that HDAC2 is a direct target of cAMP response element-binding protein (CREB) that is activated by beta-adrenergic signaling. Notably, HDAC2 is necessary for beta-adrenergic signaling to induce angiogenesis. We further demonstrated that, upon CREB activation, HDAC2 represses thrombospondin-1 (TSP1), a potent angiogenesis inhibitor, through epigenetic regulation. Together, these data establish a novel pathway that HDAC2 and TSP1 act downstream of CREB activation in beta-adrenergic signaling to promote cancer progression.

Giant impacts in the Beta Pic system

NASA Astrophysics Data System (ADS)

Jackson, A.

2014-09-01

One scenario that can potentially explain the brightness asymmetry in the Beta Pictoris debris disk in the mid-infrared and millimetre is that of a comparatively recent (< 1 Myr ago) impact between planetary scale bodies at an orbital distance of ˜85 AU, as discussed by Dent et al 2014. I will discuss the details of this model, how it applies to Beta Pictoris, and how it may be applied elsewhere.

Is an absolute level of cortical beta suppression required for proper movement? Magnetoencephalographic evidence from healthy aging.

PubMed

Heinrichs-Graham, Elizabeth; Wilson, Tony W

2016-07-01

Previous research has connected a specific pattern of beta oscillatory activity to proper motor execution, but no study to date has directly examined how resting beta levels affect motor-related beta oscillatory activity in the motor cortex. Understanding this relationship is imperative to determining the basic mechanisms of motor control, as well as the impact of pathological beta oscillations on movement execution. In the current study, we used magnetoencephalography (MEG) and a complex movement paradigm to quantify resting beta activity and movement-related beta oscillations in the context of healthy aging. We chose healthy aging as a model because preliminary evidence suggests that beta activity is elevated in older adults, and thus by examining older and younger adults we were able to naturally vary resting beta levels. To this end, healthy younger and older participants were recorded during motor performance and at rest. Using beamforming, we imaged the peri-movement beta event-related desynchronization (ERD) and extracted virtual sensors from the peak voxels, which enabled absolute and relative beta power to be assessed. Interestingly, absolute beta power during the pre-movement baseline was much stronger in older relative to younger adults, and older adults also exhibited proportionally large beta desynchronization (ERD) responses during motor planning and execution compared to younger adults. Crucially, we found a significant relationship between spontaneous (resting) beta power and beta ERD magnitude in both primary motor cortices, above and beyond the effects of age. A similar link was found between beta ERD magnitude and movement duration. These findings suggest a direct linkage between beta reduction during movement and spontaneous activity in the motor cortex, such that as spontaneous beta power increases, a greater reduction in beta activity is required to execute movement. We propose that, on an individual level, the primary motor cortices have an absolute threshold of beta power that must be reached in order to move, and that an inability to suppress beta power to this threshold results in an increase in movement duration. Copyright © 2016 Elsevier Inc. All rights reserved.

Use of beta-methylphenylalanine (beta MeF) residues to probe the nature of the interaction of substance P with its receptor: effects of beta MeF-containing substance P analogs on rabbit iris smooth muscle contraction.

PubMed

Birney, D M; Cole, D C; Crosson, C E; Kahl, B F; Neff, B W; Reid, T W; Ren, K; Walkup, R D

1995-06-23

The effects of substituting (2S,3S)-beta-methylphenylalanine (S-beta MeF) or (2S,3R)-beta-methylphenylalanine (R-beta MeF) for the Phe7 and/or Phe8 residues of the tachykinin substance P (SP, RPKPQQFFGLM-NH2) upon the ability of SP to stimulate contraction of the rabbit iris smooth muscle were investigated. The eight beta MeF-containing SP analogs (four monosubstituted analogs, four disubstituted analogs) 1-8 were synthesized and found to be agonsts of SP in the smooth muscle contraction assay, having EC50 values ranging from 0.15 to 10.0 nM. Three analogs are significantly more active than SP [8R-(beta MeF)SP (4), 7S,8S-(beta MeF)2SP (5), and 7R,8S-(beta MeF)2SP (6)], three analogs are approximately equipotent with SP [7S-(beta MeF)SP (1), 7R-(beta MeF)SP (2), and 7S,8R-(beta MeF)2SP (8)], and two analogs are significantly less active than SP [8S-(beta MeF)SP (3) and 7R,8R-(beta MeF)2SP (7)]. The effects of the beta MeF substitutions upon the activity of SP are not additive and cannot be explained using simple conformational models which focus only on the side chain conformations of the beta MeF residues. It is postulated that the beta MeF residues induce minor distortions in the peptide backbone with resultant consequences upon peptide-receptor binding which are not dictated soley by the side chain conformations. This idea is consistent with 1H-NMR data for the monosubstituted analogs 1-4, which imply that the beta MeF substitutions cause slight distortions in the peptide backbone and that the beta MeF side chains are assuming trans or gauche(-) conformations.

High-fat, carbohydrate-free diet markedly aggravates obesity but prevents beta-cell loss and diabetes in the obese, diabetes-susceptible db/db strain.

PubMed

Mirhashemi, Farshad; Kluth, Oliver; Scherneck, Stephan; Vogel, Heike; Kluge, Reinhart; Schurmann, Annette; Joost, Hans-Georg; Neschen, Susanne

2008-01-01

We have previously reported that a high-fat, carbohydrate-free diet prevents diabetes and beta-cell destruction in the New Zealand Obese (NZO) mouse strain. Here we investigated the effect of diets with and without carbohydrates on obesity and development of beta-cell failure in a second mouse model of type 2 diabetes, the db/db mouse. When kept on a carbohydrate-containing standard (SD; with (w/w) 5.1, 58.3, and 17.6% fat, carbohydrates and protein, respectively) or high-fat diet (HFD; 14.6, 46.7 and 17.1%), db/db mice developed severe diabetes (blood glucose >20 mmol/l, weight loss, polydipsia and polyurea) associated with a selective loss of pancreatic beta-cells, reduced GLUT2 expression in the remaining beta-cells, and reduced plasma insulin levels. In contrast, db/db mice kept on a high-fat, carbohydrate-free diet (CFD; with 30.2 and 26.4% (w/w) fat or protein) did not develop diabetes and exhibited near-normal, hyperplastic islets in spite of a morbid obesity (fat content >60%) associated with hyperinsulinaemia. These data indicate that in genetically different mouse models of obesity-associated diabetes, obesity and dietary fat are not sufficient, and dietary carbohydrates are required, for beta-cell destruction.

Hydrogen sulfide protects cardiomyocytes from hypoxia/reoxygenation-induced apoptosis by preventing GSK-3beta-dependent opening of mPTP.

PubMed

Yao, Ling-Ling; Huang, Xiao-Wei; Wang, Yong-Gang; Cao, Yin-Xiang; Zhang, Cai-Cai; Zhu, Yi-Chun

2010-05-01

Hydrogen sulfide (H(2)S) is an endogenously generated gaseous transmitter, which has recently been suggested to regulate cardiovascular functions. The present study aims to clarify the mechanisms underlying the cardioprotective effects of H(2)S. Signaling elements were examined in cardiomyocytes cultured under hypoxia/reoxygenation conditions and in a rat model of ischemia-reperfusion. In cultured cardiomyocytes, sodium hydrosulfide (NaHS; 10, 30, and 50 mumol/l) showed concentration-dependent inhibitory effects on cardiomyocyte apoptosis induced by hypoxia/reoxygenation. These effects were associated with an increase in phosphorylation of glycogen synthase kinase-3beta (GSK-3beta) (Ser9) and a decrease in Bax translocation, caspase-3 activation, and mitochondrial permeability transition pore (mPTP) opening. Transfection of a phosphorylation-resistant mutant of GSK-3beta at Ser9 attenuated the effects of NaHS in reducing cardiomyocyte apoptosis, Bax translocation, caspase-3 activation, and mPTP opening. In a rat model of ischemia-reperfusion, NaHS administration reduced myocardial infarct size and increased the phosphorylation of GSK-3beta (Ser9) at a dose of 30 mumol/kg. In conclusion, the H(2)S donor prevents cardiomyocyte apoptosis by inducing phosphorylation of GSK-3beta (Ser9) and subsequent inhibition of mPTP opening.

Towards Alzheimer's beta-amyloid vaccination.

PubMed

Frenkel, D; Solomon, B

2001-01-01

Beta-amyloid pathology, the main hallmark of Alzheimer's disease (AD), has been linked to its conformational status and aggregation. We recently showed that site-directed monoclonal antibodies (mAbs) towards the N-terminal region of the human beta-amyloid peptide bind to preformed beta-amyloid fibrils (Abeta), leading to disaggregation and inhibition of their neurotoxic effect. Here we report the development of a novel immunization procedure to raise effective anti-aggregating amyloid beta-protein (AbetaP) antibodies, using as antigen filamentous phages displaying the only EFRH peptide found to be the epitope of these antibodies. Due to the high antigenicity of the phage no adjuvant is required to obtain high affinity anti-aggregating IgG antibodies in animals model, that exhibit identity to human AbetaP. Such antibodies are able to sequester peripheral AbetaP, thus avoiding passage through the blood brain barrier (BBB) and, as recently shown in a transgenic mouse model, to cross the BBB and dissolve already formed beta-amyloid plaques. To our knowledge, this is the first attempt to use as a vaccine a self-anti-aggregating epitope displayed on a phage, and this may pave the way to treat abnormal accumulation-peptide diseases, such as Alzheimer's disease or other amyloidogenic diseases. Copyright 2001 The International Association for Biologicals.

In Situ FTIR Microspectroscopy of Brain Tissue from a Transgenic Mouse Model of Alzheimer Disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rak,M.; Del Bigio, M.; Mai, S.

2007-01-01

Plaques composed of the A{beta} peptide are the main pathological feature of Alzheimer's disease. Dense-core plaques are fibrillar deposits of A{beta}, showing all the classical properties of amyloid including {beta}-sheet secondary structure, while diffuse plaques are amorphous deposits. We studied both plaque types, using synchrotron infrared (IR) microspectroscopy, a technique that allows the chemical composition and average protein secondary structure to be investigated in situ. We examined plaques in hippocampal, cortical and caudal tissue from 5- to 21-month-old TgCRND8 mice, a transgenic model expressing doubly mutant amyloid precursor protein, and displaying impaired hippocampal function and robust pathology from an earlymore » age. Spectral analysis confirmed that the congophilic plaque cores were composed of protein in a {beta}-sheet conformation. The amide I maximum of plaque cores was at 1623 cm-1, and unlike for in vitro A{beta} fibrils, the high-frequency (1680-1690 cm-1) component attributed to antiparallel {beta}-sheet was not observed. A significant elevation in phospholipids was found around dense-core plaques in TgCRND8 mice ranging in age from 5 to 21 months. In contrast, diffuse plaques were not associated with IR detectable changes in protein secondary structure or relative concentrations of any other tissue components.« less

Sources of stress and psychological morbidity among undergraduate physiotherapy students.

PubMed

Walsh, J M; Feeney, C; Hussey, J; Donnellan, C

2010-09-01

Professional education can be a stressful experience for some individuals, and may impact negatively on emotional well-being and academic performance. Psychological morbidity and associated sources of stress have not been investigated extensively in physiotherapy students. This study explored sources of stress, psychological morbidity and possible associations between these variables in undergraduate physiotherapy students. A questionnaire-based survey. The Undergraduate Sources of Stress Questionnaire was used to identify sources of stress, and the General Health Questionnaire-12 (GHQ-12) was used to rate the prevalence of psychological morbidity, using a conservative GHQ threshold of 3 to 4 to determine probable 'cases'. Uni- and multivariate tests of correlation were used to analyse the data. An Irish educational institution. One hundred and twenty-five physiotherapy undergraduate students. More than one-quarter of all students (27%) scored above the GHQ threshold, indicating probable psychological morbidity. This is higher than the level of psychological morbidity reported by the general population. Regression analysis showed that academic (beta=0.31, P<0.001) and personal (beta=0.50, P<0.001) sources of stress subscales were significant coefficients, explaining 48% of the variance in psychological morbidity after controlling for part-time employment and hours spent studying. Individual significant items from these subscales were stressful events (beta=0.24, P=0.004), mood (beta=0.43, P< or =0.001) and overall level of stress (beta=0.35, P< or =0.001). The results highlighted the emotional vulnerability of a significant proportion of physiotherapy students, with academic and personal issues being the greatest concern. While personal causes of stress such as stressful events and mood are more difficult to control, manipulation of curricular factors may have positive effects on academic sources of stress. Copyright 2010 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.

Cooperative alpha-helix formation of beta-lactoglobulin induced by sodium n-alkyl sulfates.

PubMed

Chamani, J; Moosavi-Movahedi, A A; Rajabi, O; Gharanfoli, M; Momen-Heravi, M; Hakimelahi, G H; Neamati-Baghsiah, A; Varasteh, A R

2006-01-01

It is generally assumed that folding intermediates contain partially formed native-like secondary structures. However, if we consider the fact that the conformational stability of the intermediate state is simpler than that of the native state, it would be expected that the secondary structures in a folding intermediate would not necessarily be similar to those of the native state. beta-Lactoglobulin is a predominantly beta-sheet protein, although it has a markedly high intrinsic preference for alpha-helical structure. The formation of non-native alpha-helical intermediate of beta-lactoglobulin was induced by n-alkyl sulfates including sodium octyl sulfate, SOS; sodium decyl sulfate, SDeS; sodium dodecyl sulfate, SDS; and sodium tetradecyl sulfate, STS at special condition. The effect of n-alkyl sulfates on the structure of native beta-lactoglobulin at pH 2 was utilized to investigate the contribution of hydrophobic interactions to the stability of non-native alpha-helical intermediate. The addition of various concentrations of n-alkyl sulfates to the native state of beta-lactoglobulin (pH 2) appears to support the stabilized form of non-native alpha-helical intermediate at pH 2. The m values of the intermediate state of beta-lactoglobulin by SOS, SDeS, SDS and STS showed substantial variation. The enhancement of m values as the stability criterion of non-native alpha-helical intermediate state corresponded with increasing chain length of the cited n-alkyl sulfates. The present results suggest that the folding reaction of beta-lactoglobulin follows a non-hierarchical mechanism and hydrophobic interactions play important roles in stabilizing the non-native alpha-helical intermediate state.

Production of beta-glucan and related glucan-hydrolases by Botryosphaeria rhodina.

PubMed

Crognale, S; Bruno, M; Fidaleo, M; Moresi, M; Petruccioli, M

2007-03-01

Characterization of beta-glucan production from Botryosphaeria rhodina DABAC-P82 by detecting simultaneously glucan-hydrolytic enzymes and their localization, culture medium rheology and oxygen transfer. Mycelium growth, beta-glucan production, substrate consumption and glucan-hydrolytic enzymes were monitored both in shaken flasks and in a 3-l stirred-tank bioreactor. Glucan production (19.7 and 15.2 g l(-1), in flask and bioreactor, respectively) was accompanied by extra-cellular and cell-bound beta-glucanase and beta-glucosidase activities. In the bioreactor scale, in the time interval of 0-78 h the apparent viscosity of the culture broth exhibited a general increase; thereafter, it began to reduce, probably because of the above glucan-hydrolytic activities. Moreover, the culture media collected after 45 h behaved as solid-like materials at shear rates smaller than 0.001 s(-1), as pseudo-plastic liquids in the middle shear rate range and as Newtonian ones at shear rates greater than 1000 s(-1). The greatest beta-glucan accumulation in the bioreactor was found to be associated with nitrogen and dissolved oxygen concentrations smaller than 0.15 g l(-1) and 25%, respectively, and with the peak points of the glucan-degrading enzymes. A careful analysis of the critical factors (such as, culture broth rheology, oxygen mass transfer and glucan-hydrolytic enzymes) limiting the beta-glucan production by B. rhodina is a prerequisite to maximize beta-glucan yield and production, as well as to define the process flow sheet capable of maximizing biopolymer recovery, solvent re-utilization and glucose consumption.

Assessing Impacts of Global Warming on Tropical Cyclone Tracks

NASA Technical Reports Server (NTRS)

Wu, Li-Guang; Wang, Bin

2003-01-01

A new approach is proposed to assess the possible impacts of the global climate change on tropical cyclone (TC) tracks in the western North Pacific (WNP) basin. The idea is based on the premise that the future change of TC track characteristics is primarily determined by changes in large-scale environmental steering flows. It is demonstrated that the main characteristics of the current climatology of TC tracks can be derived from the climatological mean velocity field of TC motion by using a trajectory model. The climatological mean velocity of TC motion, which is composed of the large-scale steering and beta drift, is determined on each grid of the basin. The mean beta drift is estimated from the best track data, and the mean large-scale steering flow is computed from the NCEP/NCAR reanalysis for the current climate state. The derived mean beta drift agrees well with the results of previous observational and numerical studies in terms of its direction and magnitude. The outputs of experiments A2 and B2 of the Geophysical Fluid Dynamics Laboratory (GFDL) R30 climate model suggest that the subtropical high will be persistently weak over the western part of the WNP or shift eastward during July-September in response to the future climate change. By assuming that the mean beta drift in the future climate state is unchanged, the change in the general circulation by 2059 will decrease the TC activities in the WNP, but favor a northward shift of typical TC tracks. As a result, the storm activities in the South China Sea will decrease by about 12%, while the Japan region will experience an increase of TCs by 12-15%. During the period of 2000-2029, the tropical storms that affect the China region will increase by 5-6%, but return to the current level during 2030-2059. It is also suggested that, during the period of 2030-2059 tropical storms will more frequently affect Japan and the middle latitude region of China given that the formation locations remain the same as in the current climate state.

51 OPHIUCHUS: A POSSIBLE BETA PICTORIS ANALOG MEASURED WITH THE KECK INTERFEROMETER NULLER

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stark, Christopher C.; Kuchner, Marc J.; Traub, Wesley A.

2009-10-01

We present observations of the 51 Ophiuchi circumstellar disk made with the Keck interferometer operating in nulling mode at N band. We model these data simultaneously with VLTI-MIDI visibility data and a Spitzer IRS spectrum using a variety of optically thin dust cloud models and an edge-on optically thick disk model. We find that single-component optically thin disk models and optically thick disk models are inadequate to reproduce the observations, but an optically thin two-component disk model can reproduce all of the major spectral and interferometric features. Our preferred disk model consists of an inner disk of blackbody grains extendingmore » to {approx}4 AU and an outer disk of small silicate grains extending out to {approx}1200 AU. Our model is consistent with an inner 'birth' disk of continually colliding parent bodies producing an extended envelope of ejected small grains. This picture resembles the disks around Vega, AU Microscopii, and beta Pictoris, supporting the idea that 51 Ophiuchius may be a beta Pictoris analog.« less

Combining the LKB NTCP model with radiosensitivity parameters to characterize toxicity of radionuclides based on a multiclonogen kidney model: a theoretical assessment.

PubMed

Lin, Hui; Jing, Jia; Xu, Liangfeng; Wu, Dongsheng; Xu, Yuanying

2012-06-01

The Lyman-Kutcher-Burman (LKB) normal tissue complication probability (NTCP) model is often used to estimate the damage level to normal tissue. However, it does not manifestly involve the influence of radiosensitivity parameters. This work replaces the generalized mean equivalent uniform dose (gEUD) with the equivalent uniform dose (EUD) in the LKB model to investigate the effect of a variety of radiobiological parameters on the NTCP to characterize the toxicity of five types of radionuclides. The dose for 50 % complication probability (D (50)) is replaced by the corresponding EUD for 50 % complication probability (EUD(50)). The properties of a variety of radiobiological characteristics, such as biologically effective dose (BED), NTCP, and EUD, for five types of radioisotope ((131)I, (186)Re, (188)Re, (90)Y, and (67)Cu) are investigated by various radiosensitivity parameters such as intrinsic radiosensitivity α, alpha-beta ratio α/β, cell repair half-time, cell mean clonogen doubling time, etc. The high-energy beta emitters ((90)Y and (188)Re) have high initial dose rate and mean absorbed dose per injected activity in kidney, and their kidney toxicity should be of greater concern if they are excreted through kidneys. The radiobiological effect of (188)Re changes most sharply with the radiobiological parameters due to its high-energy electrons and very short physical half-life. The dose for a probability of 50% injury within 5y (D (50/5)) 28 Gy for whole-kidney irradiation should be adjusted according to different radionuclides and different radiosensitivity of individuals. The D (50/5) of individuals with low α/β or low α, or low biological clearance half-time, will be less than 28 Gy. The 50 % complication probability dose for (67)Cu and (188)Re could be 25 Gy and 22 Gy. The same mean absorbed dose generally corresponds to different degrees of damage for tissues of different radiosensitivity and different radionuclides. The influence of various radiobiological parameters should be taken into consideration in the NTCP model.

Mapping CHU9D Utility Scores from the PedsQLTM 4.0 SF-15.

PubMed

Mpundu-Kaambwa, Christine; Chen, Gang; Russo, Remo; Stevens, Katherine; Petersen, Karin Dam; Ratcliffe, Julie

2017-04-01

The Pediatric Quality of Life Inventory™ 4.0 Short Form 15 Generic Core Scales (hereafter the PedsQL) and the Child Health Utility-9 Dimensions (CHU9D) are two generic instruments designed to measure health-related quality of life in children and adolescents in the general population and paediatric patient groups living with specific health conditions. Although the PedsQL is widely used among paediatric patient populations, presently it is not possible to directly use the scores from the instrument to calculate quality-adjusted life-years (QALYs) for application in economic evaluation because it produces summary scores which are not preference-based. This paper examines different econometric mapping techniques for estimating CHU9D utility scores from the PedsQL for the purpose of calculating QALYs for cost-utility analysis. The PedsQL and the CHU9D were completed by a community sample of 755 Australian adolescents aged 15-17 years. Seven regression models were estimated: ordinary least squares estimator, generalised linear model, robust MM estimator, multivariate factorial polynomial estimator, beta-binomial estimator, finite mixture model and multinomial logistic model. The mean absolute error (MAE) and the mean squared error (MSE) were used to assess predictive ability of the models. The MM estimator with stepwise-selected PedsQL dimension scores as explanatory variables had the best predictive accuracy using MAE and the equivalent beta-binomial model had the best predictive accuracy using MSE. Our mapping algorithm facilitates the estimation of health-state utilities for use within economic evaluations where only PedsQL data is available and is suitable for use in community-based adolescents aged 15-17 years. Applicability of the algorithm in younger populations should be assessed in further research.

Beta Peak Frequencies at Rest Correlate with Endogenous GABA+/Cr Concentrations in Sensorimotor Cortex Areas

PubMed Central

Baumgarten, Thomas J.; Oeltzschner, Georg; Hoogenboom, Nienke; Wittsack, Hans-Jörg; Schnitzler, Alfons; Lange, Joachim

2016-01-01

Neuronal oscillatory activity in the beta band (15–30 Hz) is a prominent signal within the human sensorimotor cortex. Computational modeling and pharmacological modulation studies suggest an influence of GABAergic interneurons on the generation of beta band oscillations. Accordingly, studies in humans have demonstrated a correlation between GABA concentrations and power of beta band oscillations. It remains unclear, however, if GABA concentrations also influence beta peak frequencies and whether this influence is present in the sensorimotor cortex at rest and without pharmacological modulation. In the present study, we investigated the relation between endogenous GABA concentration (measured by magnetic resonance spectroscopy) and beta oscillations (measured by magnetoencephalography) at rest in humans. GABA concentrations and beta band oscillations were measured for left and right sensorimotor and occipital cortex areas. A significant positive linear correlation between GABA concentration and beta peak frequency was found for the left sensorimotor cortex, whereas no significant correlations were found for the right sensorimotor and the occipital cortex. The results show a novel connection between endogenous GABA concentration and beta peak frequency at rest. This finding supports previous results that demonstrated a connection between oscillatory beta activity and pharmacologically modulated GABA concentration in the sensorimotor cortex. Furthermore, the results demonstrate that for a predominantly right-handed sample, the correlation between beta band oscillations and endogenous GABA concentrations is evident only in the left sensorimotor cortex. PMID:27258089

Mesalamine inhibits epithelial beta-catenin activation in chronic ulcerative colitis.

PubMed

Brown, Jeffrey B; Lee, Goo; Managlia, Elizabeth; Grimm, Gery R; Dirisina, Ramanarao; Goretsky, Tatiana; Cheresh, Paul; Blatner, Nichole R; Khazaie, Khashayarsha; Yang, Guang-Yu; Li, Linheng; Barrett, Terrence A

2010-02-01

Mesalamine is a mainstay therapeutic agent in chronic ulcerative colitis (CUC) in which condition it reverses crypt architectural changes and reduces colitis-associated cancer (CAC). The present study addressed the possibility that mesalamine reduces beta-catenin-associated progenitor cell activation, Akt-phosphorylated beta-catenin(Ser552) (P-beta-catenin), and colitis-induced dysplasia (CID). Effects of mesalamine on P-beta-catenin staining and function were assessed by immunohistochemistry and quantitative reverse-transcription polymerase chain reaction (qRT-PCR) in biopsy specimens of CUC in mild or "refractory" severe mucosal inflammation. Effects of mesalamine on epithelial proliferation and activation of Akt and beta-catenin were assessed in interleukin (IL)-10(-/-) colitis and CID by immunohistochemistry and Western blotting. Dysplasia was assessed by counting the number and lengths of lesions per colon. Data from IL-10(-/-) and human colitis samples show that mesalamine reduced Akt activation and P-beta-catenin levels in the middle and upper crypt. Reductions in P-beta-catenin in CUC biopsy specimens with severe inflammation suggested that mesalamine reduced P-beta-catenin levels in tissue refractory to mesalamine's anti-inflammatory effects. In IL-10(-/-) mice, mesalamine reduced CID concordant with inhibition of crypt Akt and beta-catenin signaling. The results are consistent with the model that mesalamine contributes to chemoprevention in CAC by reducing beta-catenin signaling within intestinal progenitors.

Discrete wavelet approach to multifractality

NASA Astrophysics Data System (ADS)

Isaacson, Susana I.; Gabbanelli, Susana C.; Busch, Jorge R.

2000-12-01

The use of wavelet techniques for the multifractal analysis generalizes the box counting approach, and in addition provides information on eventual deviations of multifractal behavior. By the introduction of a wavelet partition function Wq and its corresponding free energy (beta) (q), the discrepancies between (beta) (q) and the multifractal free energy r(q) are shown to be indicative of these deviations. We study with Daubechies wavelets (D4) some 1D examples previously treated with Haar wavelets, and we apply the same ideas to some 2D Monte Carlo configurations, that simulate a solution under the action of an attractive potential. In this last case, we study the influence in the multifractal spectra and partition functions of four physical parameters: the intensity of the pairwise potential, the temperature, the range of the model potential, and the concentration of the solution. The wavelet partition function Wq carries more information about the cluster statistics than the multifractal partition function Zq, and the location of its peaks contributes to the determination of characteristic sales of the measure. In our experiences, the information provided by Daubechies wavelet sis slightly more accurate than the one obtained by Haar wavelets.

Application of a novel design paradigm to generate general nonpeptide combinatorial templates mimicking beta-turns: synthesis of ligands for melanocortin receptors.

PubMed

Webb, Thomas R; Jiang, Luyong; Sviridov, Sergey; Venegas, Ruben E; Vlaskina, Anna V; McGrath, Douglas; Tucker, John; Wang, Jian; Deschenes, Alain; Li, Rongshi

2007-01-01

We report the further application of a novel approach to template and ligand design by the synthesis of agonists of the melanocortin receptor. This design method uses the conserved structural data from the three-dimensional conformations of beta-turn peptides to design rigid nonpeptide templates that mimic the orientation of the main chain C-alpha atoms in a peptide beta-turn. We report details on a new synthesis of derivatives of template 1 that are useful for the synthesis of exploratory libraries. The utility of this technique is further exemplified by several iterative rounds of high-throughput synthesis and screening, which result in new partially optimized nonpeptide agonists for several melanocortin receptors.

Perturbations of Jacobi polynomials and piecewise hypergeometric orthogonal systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Neretin, Yu A

2006-12-31

A family of non-complete orthogonal systems of functions on the ray [0,{infinity}] depending on three real parameters {alpha}, {beta}, {theta} is constructed. The elements of this system are piecewise hypergeometric functions with singularity at x=1. For {theta}=0 these functions vanish on [1,{infinity}) and the system is reduced to the Jacobi polynomials P{sub n}{sup {alpha}}{sup ,{beta}} on the interval [0,1]. In the general case the functions constructed can be regarded as an interpretation of the expressions P{sub n+{theta}}{sup {alpha}}{sup ,{beta}}. They are eigenfunctions of an exotic Sturm-Liouville boundary-value problem for the hypergeometric differential operator. The spectral measure for this problem ismore » found.« less

Universal binding energy relations in metallic adhesion

NASA Technical Reports Server (NTRS)

Ferrante, J.; Smith, J. R.; Rose, J. H.

1981-01-01

Scaling relations which map metallic adhesive binding energy onto a single universal binding energy curve are discussed in relation to adhesion, friction, and wear in metals. The scaling involved normalizing the energy to the maximum binding energy and normalizing distances by a suitable combination of Thomas-Fermi screening lengths. The universal curve was found to be accurately represented by E*(A*)= -(1+beta A) exp (-Beta A*) where E* is the normalized binding energy, A* is the normalized separation, and beta is the normalized decay constant. The calculated cohesive energies of potassium, barium, copper, molybdenum, and samarium were also found to scale by similar relations, suggesting that the universal relation may be more general than for the simple free electron metals.

Sickle cell crisis associated with hemophagocytic lymphohistiocytosis.

PubMed

Kio, Ebenezer; Onitilo, Adedayo; Lazarchick, John; Hanna, Maged; Brunson, Chris; Chaudhary, Uzair

2004-11-01

Sickle-beta(+) (beta(+)) thalassemia is a double heterozygous genetic disorder characterized by both a qualitative and quantitative abnormality. We present a case of an African American male who was first diagnosed with sickle cell disease (SCD) at the age 23 years when he presented with generalized bone pain, fever, and hepatosplenomegaly. Laboratory findings included thrombocytopenia, microcytic anemia, and markedly elevated ferritin. He was subsequently diagnosed with a sickle-beta thalassemia hemoglobinopathy. Findings in the bone marrow aspirate and biopsy were consistent with hemophagocytic lymphohistiocytosis (HLH). HLH resolved with the resolution of sickle cell bone pain crisis without use of immunosuppressive therapy. To the best of our knowledge this is the first documented case of HLH associated with sickle cell bone pain crisis.

Hb Hope [beta136(H14)Gly-->Asp (GGT-->GAT)]: interactions with Hb S [beta6(A3)Glu-->Val (GAG-->GTG)], other variant hemoglobins and thalassemia.

PubMed

Ingle, John; Adewoye, Adeboye; Dewan, Robert; Okoli, Michael; Rollins, Lamarr; Eung, Shawn H; Luo, Hong-Yuan; Chui, David H K; Steinberg, Martin H

2004-01-01

Hb Hope [beta136(H14)Gly-->Asp (GGT-->GAT)] was first described in an African-American family in 1965. Since then, it has been found in combination with several different globin gene mutations in many other families of divergent ethnic backgrounds. The basis for its relatively frequent occurrences remains unexplained. This variant hemoglobin (Hb) is mildly unstable and has reduced oxygen affinity, but is generally innocuous clinically. This variant Hb can present as a confounding factor in arriving at a correct diagnosis by either electrophoresis or high performance liquid chromatography (HPLC), particularly during the neonatal period. DNA-based diagnostics can help solve this potential problem.

Substrate-induced inactivation of the OXA2 beta-lactamase.

PubMed Central

Ledent, P; Frère, J M

1993-01-01

The hydrolysis time courses of 22 beta-lactam antibiotics by the class D OXA2 beta-lactamase were studied. Among these, only three appeared to correspond to the integrated Henri-Michaelis equation. 'Burst' kinetics, implying branched pathways, were observed with most penicillins, cephalosporins and with flomoxef and imipenem. Kinetic parameters characteristic of the different phases of the hydrolysis were determined for some substrates. Mechanisms generally accepted to explain such reversible partial inactivations involving branches at either the free enzyme or the acyl-enzyme were inadequate to explain the enzyme behaviour. The hydrolysis of imipenem was characterized by the occurrence of two 'bursts', and that of nitrocefin by a partial substrate-induced inactivation complicated by a competitive inhibition by the hydrolysis product. PMID:8240304

DOE Office of Scientific and Technical Information (OSTI.GOV)

Denbleyker, Alan; Liu, Yuzhi; Meurice, Y.

We consider the sign problem for classical spin models at complexmore » $$\\beta =1/g_0^2$$ on $$L\\times L$$ lattices. We show that the tensor renormalization group method allows reliable calculations for larger Im$$\\beta$$ than the reweighting Monte Carlo method. For the Ising model with complex $$\\beta$$ we compare our results with the exact Onsager-Kaufman solution at finite volume. The Fisher zeros can be determined precisely with the TRG method. We check the convergence of the TRG method for the O(2) model on $$L\\times L$$ lattices when the number of states $$D_s$$ increases. We show that the finite size scaling of the calculated Fisher zeros agrees very well with the Kosterlitz-Thouless transition assumption and predict the locations for larger volume. The location of these zeros agree with Monte Carlo reweighting calculation for small volume. The application of the method for the O(2) model with a chemical potential is briefly discussed.« less

On the Relationship between Molecular Hit Rates in High-Throughput Screening and Molecular Descriptors.

PubMed

Hansson, Mari; Pemberton, John; Engkvist, Ola; Feierberg, Isabella; Brive, Lars; Jarvis, Philip; Zander-Balderud, Linda; Chen, Hongming

2014-06-01

High-throughput screening (HTS) is widely used in the pharmaceutical industry to identify novel chemical starting points for drug discovery projects. The current study focuses on the relationship between molecular hit rate in recent in-house HTS and four common molecular descriptors: lipophilicity (ClogP), size (heavy atom count, HEV), fraction of sp(3)-hybridized carbons (Fsp3), and fraction of molecular framework (f(MF)). The molecular hit rate is defined as the fraction of times the molecule has been assigned as active in the HTS campaigns where it has been screened. Beta-binomial statistical models were built to model the molecular hit rate as a function of these descriptors. The advantage of the beta-binomial statistical models is that the correlation between the descriptors is taken into account. Higher degree polynomial terms of the descriptors were also added into the beta-binomial statistic model to improve the model quality. The relative influence of different molecular descriptors on molecular hit rate has been estimated, taking into account that the descriptors are correlated to each other through applying beta-binomial statistical modeling. The results show that ClogP has the largest influence on the molecular hit rate, followed by Fsp3 and HEV. f(MF) has only a minor influence besides its correlation with the other molecular descriptors. © 2013 Society for Laboratory Automation and Screening.

[Bioactive constituents from whole herbs of Vernonia cinerea (II)].

PubMed

Zhu, Huaxu; Tang, Yuping; Min, Zhida; Gong, Zhunan

2009-11-01

To study the constituents of the whole herbs of Vernonia cinerea by bio-activity guided isolation with PC-12 model. The constituents were separated by column chromatography and the structures were elucidated by spectroscopic methods. Ten compounds were identified to be (-)-clovane-2,9-diol (1), caryolane-1,9beta-diol (2), apigenin (3), chrysoeriol (4), luteolin (5), thermopsoside (6), luteolin-7-O-beta-D-glucoside (7), quercetin(8), apigenin-4'-O-beta-D-glucoside (9), hyperin (10), beta-amyrin aceate (11), lupeol acetate (12). Compounds 1, 2, 6 and 10 were isolated from this genus for the first time.

Linear optics measurements and corrections using an AC dipole in RHIC

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, G.; Bai, M.; Yang, L.

2010-05-23

We report recent experimental results on linear optics measurements and corrections using ac dipole. In RHIC 2009 run, the concept of the SVD correction algorithm is tested at injection energy for both identifying the artificial gradient errors and correcting it using the trim quadrupoles. The measured phase beatings were reduced by 30% and 40% respectively for two dedicated experiments. In RHIC 2010 run, ac dipole is used to measure {beta}* and chromatic {beta} function. For the 0.65m {beta}* lattice, we observed a factor of 3 discrepancy between model and measured chromatic {beta} function in the yellow ring.

Functional assay of Salmonella typhi OmpC using reconstituted large unilamellar vesicles: a general method for characterization of outer membrane proteins.

PubMed

Sundara Baalaji, N; Mathew, M K; Krishnaswamy, S

2006-10-01

The immunodominant trimeric beta-barrel outer membrane protein OmpC from Salmonella typhi, the causative agent of typhoid, has been functionally characterized here. The activity in the vesicle environment was studied in vitro using OmpC reconstituted into proteoliposomes. Passage of polysaccharides and polyethyleneglycols through OmpC has been examined to determine the permeability properties. The relative rate of neutral solute flux yields a radius of 1.1 nm for the S. typhi OmpC pore. This is almost double the pore size of Escherichia coli. This provides an example of large pore size present in the porins that form trimers as in the general bacterial porin family. The method used in this study provides a good membrane model for functional studies of porins.

Depression Among Transgender Older Adults: General and Minority Stress.

PubMed

Hoy-Ellis, Charles P; Fredriksen-Goldsen, Karen I

2017-06-01

This study aims to (a) examine the direct and indirect effects internalized heterosexism, disclosure of gender identity, and perceived general stress in association with depression among transgender older adults; and (b) to assess the relative contribution of each relationship. Secondary analyses of data from a large community-based study of older sexual and gender minorities were conducted utilizing structural equation modeling with a subsample (n = 174) of transgender adults aged 50 to 86-years old. Disclosure of gender identity had no significant direct or indirect effects on either perceived general stress or depression. Internalized heterosexism did not have a direct effect on depression, but did have a significant indirect effect through perceived general stress. Finally, perceived general stress had an additional significant direct effect on depression, over and above internalized heterosexism. Total effect sizes appear to be considerable with standardized betas greater than 5.0. Perceived general stress and internalized heterosexism independently and cumulatively have significant direct and indirect effects on depression among transgender older adults. Implications for depression among transgender older adults and the role of community psychology are discussed. © Society for Community Research and Action 2017.

Do changes in S100beta protein correlate with serum magnesium concentrations in patients undergoing extracorporeal circulation?

PubMed

Dabrowski, Wojciech

2007-09-01

There are many biochemical markers demonstrating the central nervous system (CNS) damage following coronary artery bypass grafting (CABG). The protein S100beta is one of them and its concentrations depend on the severity of CNS damage. On the other hand, it is well known that the brain injury results in a decrease in brain magnesium (Mg) concentration, which is strictly correlated with the serum Mg concentration. Therefore, analysis of the correlation between serum total Mg and S100beta concentrations may be important and interesting, particularly in patients undergoing surgical myocardial revascularization. Patients undergoing CABG with extracorporeal circulation under general anaesthesia were included in the study. Serum Mg and S100beta concentrations were measured at 5 measurement points: 1) just after the radial artery cannulation, 2) 10 min after completion of ECC, 3) just after surgery, 4) in the morning of the 1st postoperative day, 5) in the morning of the 2nd postoperative day. The Kruskall-Wallis ANOVA and Spearman correlation tests were used; p < 0.05 was considered as significant. Twenty male patients, aged 54-70 years (63.3 +/- 49.5) were examined. The mean blood concentration of S100beta was 0.13 microg/L +/- 0.08 and of Mg-0.99mmol/L +/- 0.13 at measurement point 1. S100beta increased from point 2 to 4. Mg decreased at points 2 and 3. Moreover, there were significant negative correlations between S100beta and Mg at point 3 and 4 (p < 0.001; R = -0.76; p < 0.05; R = -0.5, respectively) and between Mg at point 1 and S100beta at point 3 and 5 (p < 0.05, R = -0.498; p < 0.05, R = -0.488, respectively), Mg at point 2 and S100beta at point 4 (p < 0.05, R = -0.523) as well as Mg at point 4 and S100beta at point 5 (p < 0.01, R = -0.584). 1) S100beta increased while total Mg decreased during CABG, 2) The highest serum S100beta concentrations were noted just after surgery, 3) The changes in serum S100beta concentrations correlated with those in serum total Mg concentrations, 4) The decrease in serum magnesium concentrations resulted in an elevation in serum S100beta concentrations.

Peginterferon beta-1a versus other self-injectable disease-modifying therapies in the treatment of relapsing-remitting multiple sclerosis in Scotland: a cost-effectiveness analysis.

PubMed

Hernandez, Luis; Guo, Shien; Toro-Diaz, Hector; Carroll, Stuart; Syed Farooq, Syed Feisal

2017-03-01

Peginterferon beta-1a 125 mcg administered subcutaneously every 2 weeks, a new disease-modifying therapy (DMT) for relapsing-remitting multiple sclerosis (RRMS), was approved in January 2015 by the Scottish Medicines Consortium. This study assesses long-term clinical and economic outcomes of peginterferon beta-1a compared with other self-injectable DMTs (interferon beta-1a [22 mcg, 30 mcg, and 44 mcg], interferon beta-1b, and glatiramer acetate 20 mg) in the treatment of RRMS, from the National Health Service and Personal Social Services perspective in Scotland. A previously published, validated Markov cohort model was adapted for this analysis. The model estimates changes in patient disability, occurrence of relapses, and other adverse events, and translates them into quality-adjusted life years and costs. Natural history data came from the ADVANCE trial of peginterferon beta-1a, the London Ontario (Canada) database, and a large population-based MS survey in the UK. The comparative efficacy of each DMT vs placebo was obtained from a network meta-analysis. Costs (2015 British Pounds) were obtained from public databases and literature. Clinical and economic outcomes were projected over 30 years and discounted at 3.5% per year. Over 30 years, peginterferon beta-1a was dominant compared with interferon beta-1a (22, 30, and 44 mcg), and interferon beta-1b, and cost-effective compared with glatiramer acetate 20 mg. Results were most sensitive to variations in each DMT's efficacy and acquisition costs. Deterministic and probabilistic sensitivity analyses confirmed the robustness of the results. The impact of improved adherence with peginterferon beta-1a on clinical and economic outcomes and the impact of subsequent DMTs after treatment discontinuation were not considered. Oral and infused DMTs were not included as comparators. Conclusion Long-term treatment with peginterferon beta-1a improves clinical outcomes, while its cost profile makes it either dominant or cost-effective compared with other self-injectable DMTs for the treatment of RRMS in Scotland.

Beta-blocker drug therapy reduces secondary cancer formation in breast cancer and improves cancer specific survival.

PubMed

Powe, Desmond G; Voss, Melanie J; Zänker, Kurt S; Habashy, Hany O; Green, Andrew R; Ellis, Ian O; Entschladen, Frank

2010-11-01

Laboratory models show that the beta-blocker, propranolol, can inhibit norepinephrine-induced breast cancer cell migration. We hypothesised that breast cancer patients receiving beta-blockers for hypertension would show reduced metastasis and improved clinical outcome. Three patient subgroups were identified from the medical records of 466 consecutive female patients (median age 57, range 28-71) with operable breast cancer and follow-up (>10 years). Two subgroups comprised 43 and 49 hypertensive patients treated with beta-blockers or other antihypertensives respectively, prior to cancer diagnosis. 374 patients formed a non-hypertensive control group. Metastasis development, disease free interval, tumour recurrence and hazards risk were statistically compared between groups. Kaplan-Meier plots were used to model survival and DM. Beta-blocker treated patients showed a significant reduction in metastasis development (p=0.026), tumour recurrence (p=0.001), and longer disease free interval (p=0.01). In addition, there was a 57% reduced risk of metastasis (Hazards ratio=0.430; 95% CI=0.200-0.926, p=0.031), and a 71% reduction in breast cancer mortality after 10 years (Hazards ratio=0.291; 95% CI=0.119-0.715, p=0.007). This proof-of-principle study showed beta-blocker therapy significantly reduces distant metastases, cancer recurrence, and cancer-specific mortality in breast cancer patients suggesting a novel role for beta-blocker therapy. A larger epidemiological study leading to randomised clinical trials is needed for breast and other cancer types including colon, prostate and ovary.

Beta-Blocker Drug Therapy Reduces Secondary Cancer Formation in Breast Cancer and Improves Cancer Specific Survival

PubMed Central

Powe, Desmond G.; Voss, Melanie J.; Zänker, Kurt S.; Habashy, Hany O.; Green, Andrew R.; Ellis, Ian O.; Entschladen, Frank

2010-01-01

Laboratory models show that the beta-blocker, propranolol, can inhibit norepinephrine-induced breast cancer cell migration. We hypothesised that breast cancer patients receiving beta-blockers for hypertension would show reduced metastasis and improved clinical outcome. Three patient subgroups were identified from the medical records of 466 consecutive female patients (median age 57, range 28-71) with operable breast cancer and follow-up (>10 years). Two subgroups comprised 43 and 49 hypertensive patients treated with beta-blockers or other antihypertensives respectively, prior to cancer diagnosis. 374 patients formed a non-hypertensive control group. Metastasis development, disease free interval, tumour recurrence and hazards risk were statistically compared between groups. Kaplan-Meier plots were used to model survival and DM. Beta-blocker treated patients showed a significant reduction in metastasis development (p=0.026), tumour recurrence (p=0.001), and longer disease free interval (p=0.01). In addition, there was a 57% reduced risk of metastasis (Hazards ratio=0.430; 95% CI=0.200-0.926, p=0.031), and a 71% reduction in breast cancer mortality after 10 years (Hazards ratio=0.291; 95% CI=0.119-0.715, p=0.007). This proof-of-principle study showed beta-blocker therapy significantly reduces distant metastases, cancer recurrence, and cancer-specific mortality in breast cancer patients suggesting a novel role for beta-blocker therapy. A larger epidemiological study leading to randomised clinical trials is needed for breast and other cancer types including colon, prostate and ovary. PMID:21317458

A methodology for efficiency optimization of betavoltaic cell design using an isotropic planar source having an energy dependent beta particle distribution.

PubMed

Theirrattanakul, Sirichai; Prelas, Mark

2017-09-01

Nuclear batteries based on silicon carbide betavoltaic cells have been studied extensively in the literature. This paper describes an analysis of design parameters, which can be applied to a variety of materials, but is specific to silicon carbide. In order to optimize the interface between a beta source and silicon carbide p-n junction, it is important to account for the specific isotope, angular distribution of the beta particles from the source, the energy distribution of the source as well as the geometrical aspects of the interface between the source and the transducer. In this work, both the angular distribution and energy distribution of the beta particles are modeled using a thin planar beta source (e.g., H-3, Ni-63, S-35, Pm-147, Sr-90, and Y-90) with GEANT4. Previous studies of betavoltaics with various source isotopes have shown that Monte Carlo based codes such as MCNPX, GEANT4 and Penelope generate similar results. GEANT4 is chosen because it has important strengths for the treatment of electron energies below one keV and it is widely available. The model demonstrates the effects of angular distribution, the maximum energy of the beta particle and energy distribution of the beta source on the betavoltaic and it is useful in determining the spatial profile of the power deposition in the cell. Copyright © 2017. Published by Elsevier Ltd.

Citrobacter diversus ULA-27 beta-lactamases. Improved purification and general properties.

PubMed Central

Amicosante, G; Oratore, A; Franceschini, N; Maccarrone, M; Strom, R; Galleni, M; Frère, J M

1988-01-01

Two chromosome-encoded beta-lactamases have been purified from Citrobacter diversus ULA-27. They exhibited slightly different isoelectric points (6.8 and 6.2) and very similar Mr values (congruent to 29,000). Their specificity spectrum was rather wide, since they hydrolysed some cephalosporins with kcat: values similar to those observed with the best penicillin substrates. Cloxacillin, methicillin and imipenem were hydrolysed very slowly. Hydrolysis of azthreonam could not be detected. Images Fig. 3. Fig. 4. PMID:3264152

Functionalized polymers for binding to solutes in aqueous solutions

DOEpatents

Smith, Barbara F.; Robison, Thomas W.

2006-11-21

A functionalized polymer for binding a dissolved molecule in an aqueous solution is presented. The polymer has a backbone polymer to which one or more functional groups are covalently linked. The backbone polymer can be such polymers as polyethylenimine, polyvinylamine, polyallylamine, and polypropylamine. These polymers are generally water-soluble, but can be insoluble when cross-linked. The functional group can be for example diol derivatives, polyol derivatives, thiol and dithiol derivatives, guest-host groups, affinity groups, beta-diphosphonic acids, and beta-diamides

Evaluation of the Majorana phases of a general Majorana neutrino mass matrix: Testability of hierarchical flavour models

NASA Astrophysics Data System (ADS)

Samanta, Rome; Chakraborty, Mainak; Ghosal, Ambar

2016-03-01

We evaluate the Majorana phases for a general 3 × 3 complex symmetric neutrino mass matrix on the basis of Mohapatra-Rodejohann's phase convention using the three rephasing invariant quantities I12, I13 and I23 proposed by Sarkar and Singh. We find them interesting as they allow us to evaluate each Majorana phase in a model independent way even if one eigenvalue is zero. Utilizing the solution of a general complex symmetric mass matrix for eigenvalues and mixing angles we determine the Majorana phases for both the hierarchies, normal and inverted, taking into account the constraints from neutrino oscillation global fit data as well as bound on the sum of the three light neutrino masses (Σimi) and the neutrinoless double beta decay (ββ0ν) parameter |m11 |. This methodology of finding the Majorana phases is applied thereafter in some predictive models for both the hierarchical cases (normal and inverted) to evaluate the corresponding Majorana phases and it is shown that all the sub cases presented in inverted hierarchy section can be realized in a model with texture zeros and scaling ansatz within the framework of inverse seesaw although one of the sub cases following the normal hierarchy is yet to be established. Except the case of quasi degenerate neutrinos, the methodology obtained in this work is able to evaluate the corresponding Majorana phases, given any model of neutrino masses.

Derivation and validation of a simple clinical risk-model in heart failure based on 6 minute walk test performance and NT-proBNP status--do we need specificity for sex and beta-blockers?

PubMed

Frankenstein, L; Goode, K; Ingle, L; Remppis, A; Schellberg, D; Nelles, M; Katus, H A; Clark, A L; Cleland, J G F; Zugck, C

2011-02-17

It is unclear whether risk prediction strategies in chronic heart failure (CHF) need to be specific for sex or beta-blockers. We examined this problem and developed and validated the consequent risk models based on 6-minute-walk-test and NT-proBNP. The derivation cohort comprised 636 German patients with systolic dysfunction. They were validated against 676 British patients with similar aetiology. ROC-curves for 1-year mortality identified cut-off values separately for specificity (none, sex, beta-blocker, both). Patients were grouped according to number of cut-offs met (group I/II/III - 0/1/2 cut-offs). Widest separation between groups was achieved with sex- and beta-blocker-specific cut offs. In the derivation population, 1-year mortality was 0%, 8%, 31% for group I, II and III, respectively. In the validation population, 1-year rates in the three risk groups were 2%, 7%, 14%, respectively, after application of the same cut-offs. Risk stratification for CHF should perhaps take sex and beta-blocker usage into account. We derived and independently validated relevant risk models based on 6-minute-walk-tests and NT-proBNP. Specifying sex and use of beta-blockers identified three distinct sub-groups with widely differing prognosis. In clinical practice, it may be appropriate to tailor the intensity of follow-up and/or the treatment strategy according to the risk-group. Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.

[Controlling effect of bushen huatan compound on the insulin signal conducting molecule inside ovaries in polycystic ovary syndrome model rats].

PubMed

Liang, Chen; Cong, Jing; Chang, Hui

2011-12-01

To study the effects of Bushen Huatan Compound (BHC) on the glycolipid metabolism and the expressions of the insulin signal conducting molecules inside ovaries in polycystic ovary syndrome (PCOS) model rats. Female Wistar rats were subcutaneously injected with 2.5 mg/kg testosterone propionate (Their female offspring were randomly divided into the medication group and the model group, 10 in each.) or neutral tea oil of the same dose (Ten female offspring was taken as the control group.) on the 16th day of pregnancy, once daily, for 3 successive days. BHC was given to rats in the medication group by gastrogavage, while equal volume of distilled water was given to rats in the model group and the control group by gastrogavage, both once daily for 20 successive days. The body weight and ovary weight were weighed to calculate the ratio of wet fat weight/body weight. The blood glucose levels were detected at 0, 0.5, 1, and 2 h using oral glucose tolerance test (OGTT). The serum concentrations of high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), fasting blood glucose (FBG), and insulin were detected to calculate homeostasis model assessment of insulin resistance (HOMA-IR). The expressions of protein kinase B (AKT2), glycogen synthase kinase-3beta (GSK3beta), glucose transporter-4 (GLUT4), extracellular signal regulated kinase-1 (ERK1) protein, P-AKT2, P-GSK3beta, and P-ERK1 in ovaries were detected using Western blot. Compared with the control group, the ratio of wet fat weight/ body weight, the blood glucose levels at 0.5 and 2 h in OGTT, and HOMA-IR all obviously increased, and the HDL-C level obviously decreased in the model group (P < 0.05). Compared with the model group, the ratio of wet fat weight/body weight and the blood glucose levels at 2 h in OGTT obviously decreased, and the HDL-C level obviously increased in the medication group (P < 0.05). The expressions of AKT2, P-AKT2, GSK3beta, P-GSK3beta, GLUT4, and ERK1 in the ovary tissue were obviously lower in the model group than in the control group (P < 0.05). The expressions of GSK3beta, P-GSK3beta, and GLUT4 were more obviously enhanced in the medication group than in the model group (P < 0.05). Insulin resistance and glucolipid metabolism dysfunction existed in female PCOS rats. Besides, abnormal insulin signaling pathway existed in the ovary tissue. BHC could remarkably ameliorate the IR degree and glucolipid metabolism functions, and might be correlated with regulating the protein expressions of insulin signal conducting molecules.

Effects of exendin-4 on glucose tolerance, insulin secretion, and beta-cell proliferation depend on treatment dose, treatment duration and meal contents

DOE Office of Scientific and Technical Information (OSTI.GOV)

Arakawa, Masayuki; Ebato, Chie; Mita, Tomoya

2009-12-18

Beta-cell proliferation is regulated by various metabolic demands including peripheral insulin resistance, obesity, and hyperglycemia. In addition to enhancement of glucose-induced insulin secretion, agonists for glucagon-like peptide-1 receptor (GLP-1R) stimulate proliferation and inhibit apoptosis of beta-cells, thereby probably preserve beta-cell mass. To evaluate the beta-cell preserving actions of GLP-1R agonists, we assessed the acute and chronic effects of exendin-4 on beta-cell proliferation, mass and glucose tolerance in C57BL/6J mice under various conditions. Short-term administration of high-dose exendin-4 transiently stimulated beta-cell proliferation. Comparative transcriptomic analysis showed upregulation of IGF-1 receptor and its downstream effectors in islets. Treatment of mice with exendin-4more » daily for 4 weeks (long-term administration) and feeding high-fat diet resulted in significant inhibition of weight gain and improvement of glucose tolerance with reduced insulin secretion and beta-cell mass. These findings suggest that long-term GLP-1 treatment results in insulin sensitization of peripheral organs, rather than enhancement of beta-cell proliferation and function, particularly when animals are fed high-fat diet. Thus, the effects of exendin-4 on glucose tolerance, insulin secretion, and beta-cell proliferation largely depend on treatment dose, duration of treatment and meal contents. While GLP-1 enhances proliferation of beta-cells in some diabetic mice models, our results suggest that GLP-1 stimulates beta-cell growth only when expansion of beta-cell mass is required to meet metabolic demands.« less

{beta}-Catenin stabilization imparts crypt progenitor phenotype to hyperproliferating colonic epithelia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sellin, Joseph H.; Wang Yu; Singh, Pomila

2009-01-01

Utilizing the Citrobacter rodentium (CR)-induced transmissible murine colonic hyperplasia (TMCH) model, we provide mechanistic basis of changes in {beta}-catenin/APC/CKI{epsilon} leading to progression and/or regression of hyperplasia in vivo. In response to CR-induced TMCH, crypt lengths increased significantly between days 6-27 post-infection, followed by a steep decline by day 34. {beta}-Cat{sup 45}/total {beta}-catenin were elevated on day 1 post-infection, preceding changes in crypt length, and persisted for 27 days before declining by day 34. Importantly, cellular CKI{epsilon} and {beta}-catenin co-immunoprecipitated and exhibited remarkable parallel changes in kinetics during hyperplasia/regression phases. {beta}-catenin, phosphorylated at Ser33,37 and Thr41 ({beta}-cat{sup 33,37/41}), was low tillmore » day 12, followed by gradual increase until day 27 before declining by day 34. GSK-3{beta} exhibited significant Ser{sup 9}-phosphorylation/inactivation at days 6-12 with partial recovery at days 27-34. Wild type (wt) APC (p312) levels increased at day 6 with transient proteolysis/truncation to p130 form between days 12 and 15; p312 reappeared by day 19 and returned to baseline by day 34. The kinetics of {beta}-Cat{sup 45}/{beta}-catenin nuclear accumulation and acetylation (Ac-{beta}-Cat{sup Lys49}) from days 6 to 27, followed by loss of phosphorylation/acetylation by day 34 was almost identical; Tcf-4 co-immunoprecipitated with {beta}-Cat{sup 45}/{beta}-catenin and localized immunohistochemically to {beta}-Cat{sup 41/45}-positive regions leading to elevated cyclin D1 expression, during the hyperproliferative, but not regression phases of TMCH. CKI{epsilon} mediated phosphorylation of {beta}-Cat{sup 45}, resulting in stabilization/nuclear translocation of {beta}-Cat{sup 45} may be critical for maintaining proliferation at days 6-27. Reversal of GSK-3{beta} phosphorylation and APC changes may be equally critical during the regression phase from days 27 to 34.« less

Platypus globin genes and flanking loci suggest a new insertional model for beta-globin evolution in birds and mammals.

PubMed

Patel, Vidushi S; Cooper, Steven J B; Deakin, Janine E; Fulton, Bob; Graves, Tina; Warren, Wesley C; Wilson, Richard K; Graves, Jennifer A M

2008-07-25

Vertebrate alpha (alpha)- and beta (beta)-globin gene families exemplify the way in which genomes evolve to produce functional complexity. From tandem duplication of a single globin locus, the alpha- and beta-globin clusters expanded, and then were separated onto different chromosomes. The previous finding of a fossil beta-globin gene (omega) in the marsupial alpha-cluster, however, suggested that duplication of the alpha-beta cluster onto two chromosomes, followed by lineage-specific gene loss and duplication, produced paralogous alpha- and beta-globin clusters in birds and mammals. Here we analyse genomic data from an egg-laying monotreme mammal, the platypus (Ornithorhynchus anatinus), to explore haemoglobin evolution at the stem of the mammalian radiation. The platypus alpha-globin cluster (chromosome 21) contains embryonic and adult alpha- globin genes, a beta-like omega-globin gene, and the GBY globin gene with homology to cytoglobin, arranged as 5'-zeta-zeta'-alphaD-alpha3-alpha2-alpha1-omega-GBY-3'. The platypus beta-globin cluster (chromosome 2) contains single embryonic and adult globin genes arranged as 5'-epsilon-beta-3'. Surprisingly, all of these globin genes were expressed in some adult tissues. Comparison of flanking sequences revealed that all jawed vertebrate alpha-globin clusters are flanked by MPG-C16orf35 and LUC7L, whereas all bird and mammal beta-globin clusters are embedded in olfactory genes. Thus, the mammalian alpha- and beta-globin clusters are orthologous to the bird alpha- and beta-globin clusters respectively. We propose that alpha- and beta-globin clusters evolved from an ancient MPG-C16orf35-alpha-beta-GBY-LUC7L arrangement 410 million years ago. A copy of the original beta (represented by omega in marsupials and monotremes) was inserted into an array of olfactory genes before the amniote radiation (>315 million years ago), then duplicated and diverged to form orthologous clusters of beta-globin genes with different expression profiles in different lineages.

Linking species richness curves from non-contiguous sampling to contiguous-nested SAR: An empirical study

NASA Astrophysics Data System (ADS)

Lazarina, Maria; Kallimanis, Athanasios S.; Pantis, John D.; Sgardelis, Stefanos P.

2014-11-01

The species-area relationship (SAR) is one of the few generalizations in ecology. However, many different relationships are denoted as SARs. Here, we empirically evaluated the differences between SARs derived from nested-contiguous and non-contiguous sampling designs, using plants, birds and butterflies datasets from Great Britain, Greece, Massachusetts, New York and San Diego. The shape of SAR depends on the sampling scheme, but there is little empirical documentation on the magnitude of the deviation between different types of SARs and the factors affecting it. We implemented a strictly nested sampling design to construct nested-contiguous SAR (SACR), and systematic nested but non-contiguous, and random designs to construct non-contiguous species richness curves (SASRs for systematic and SACs for random designs) per dataset. The SACR lay below any SASR and most of the SACs. The deviation between them was related to the exponent f of the power law relationship between sampled area and extent. The lower the exponent f, the higher was the deviation between the curves. We linked SACR to SASR and SAC through the concept of "effective" area (Ae), i.e. the nested-contiguous area containing equal number of species with the accumulated sampled area (AS) of a non-contiguous sampling. The relationship between effective and sampled area was modeled as log(Ae) = klog(AS). A Generalized Linear Model was used to estimate the values of k from sampling design and dataset properties. The parameter k increased with the average distance between samples and with beta diversity, while k decreased with f. For both systematic and random sampling, the model performed well in predicting effective area in both the training set and in the test set which was totally independent from the training one. Through effective area, we can link different types of species richness curves based on sampling design properties, sampling effort, spatial scale and beta diversity patterns.

Chronology of endocrine differentiation and beta-cell neogenesis.

PubMed

Miyatsuka, Takeshi

2016-01-01

Diabetes is a chronic and incurable disease, which results from absolute or relative insulin insufficiency. Therefore, pancreatic beta cells, which are the only type of cell that expresses insulin, is considered to be a potential target for the cure of diabetes. Although the findings regarding beta-cell neogenesis during pancreas development have been exploited to induce insulin-producing cells from non-beta cells, there are still many hurdles towards generating fully functional beta cells that can produce high levels of insulin and respond to physiological signals. To overcome these problems, a solid understanding of pancreas development and beta-cell formation is required, and several mouse models have been developed to reveal the unique features of each endocrine cell type at distinct developmental time points. Here I review our understanding of pancreas development and endocrine differentiation focusing on recent progresses in improving temporal cell labeling in vivo.

Precision Tests of the Electroweak Interaction using Trapped Atoms and Ions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Melconian, Daniel George

The objective of the proposed research is to study fundamental aspects of the electroweak interaction via precision measurements in beta decay to test our current understanding of fundamental particles and forces as contained in the so-called "Standard Model" of particle physics. By comparing elegant experiments to rigorous theoretical predictions, we will either confirm the Standard Model to a higher degree and rule out models which seek to extend it, or find evidence of new physics and help guide theorists in developing the New Standard Model. The use of ion and neutral atom traps at radioactive ion beam facilities has openedmore » up a new vista in precision low-energy nuclear physics experiments. Traps provide an ideal source of decaying atoms: they can be extremely cold (~1 mK); they are compact (~1 mm^3); and perhaps most importantly, the daughter particles escape with negligible distortions to their momenta in a scattering-free, open environment. The project is taking advantage of these technologies and applying them to precision beta-decay studies at radioactive beam facilities. The program consists of two complementary efforts: 1) Ion traps are an extremely versatile tool for purifying, cooling and bunching low-energy beams of short-lived nuclei. A large-bore (210~mm) superconducting 7-Tesla solenoid is at the heart of a Penning trap system for which there is a dedicated beamline at T-REX, the upgraded radioactive beam facility at the Cyclotron Institute, Texas A&M University. In addition to providing a general-purpose decay station, the flagship program for this system is measuring the ft-values and beta-neutrino correlation parameters from isospin T=2 superallowed beta-delayed proton decays, complimenting and expanding the already strong program in fundamental interactions at the Institute. 2) A magneto-optical trap is being used at the TRIUMF Neutral Atom Trap facility to observe the (un)polarized angular distribution parameters of isotopes of potassium. We are able to highly polarize laser-cooled atoms and observe their decay with unprecedented precision. The correlation of the daughter beta particle with the initial nuclear spin as well as other correlations are sensitive to physics beyond the Standard Model. Both of these cutting-edge and exciting research efforts will test our understanding of the fundamental symmetries underlying our current theory of electroweak interactions. Complementary to high-energy collider experiments, these low-energy nuclear physics "table-top" experiments will search for new particles and interactions which are not already described by the Standard Model of particle physics. The value of this research is recognized to be cross-disciplinary, exciting and potentially revolutionary in our understanding of nature's fundamental interactions. Accordingly, it has been endorsed by the recent (2007) Nuclear Science Advisory Committee's Long Range Plan as part of their recommendation for a "New Standard Model Initiative." In addition to the near-term benefits of scholarly publications and visibility through description of this work at international conferences, an important benefit of this research program is the training of new, young and enthusiastic nuclear physicists. Participants in this demanding and rewarding field develop a very strong background in physics with experience in a range of its subfields since we use atomic techniques and apply them to a nuclear physics experiment which in the end tests the theories of high-energy physics.« less

Benchmark Dose Software (BMDS) Development and ...

EPA Pesticide Factsheets

This report is intended to provide an overview of beta version 1.0 of the implementation of a model of repeated measures data referred to as the Toxicodiffusion model. The implementation described here represents the first steps towards integration of the Toxicodiffusion model into the EPA benchmark dose software (BMDS). This version runs from within BMDS 2.0 using an option screen for making model selection, as is done for other models in the BMDS 2.0 suite. This report is intended to provide an overview of beta version 1.0 of the implementation of a model of repeated measures data referred to as the Toxicodiffusion model.

Thermodynamic characterization of the interaction between prefoldin and group II chaperonin.

PubMed

Sahlan, Muhamad; Zako, Tamotsu; Tai, Phan The; Ohtaki, Akashi; Noguchi, Keiichi; Maeda, Mizuo; Miyatake, Hideyuki; Dohmae, Naoshi; Yohda, Masafumi

2010-06-18

Prefoldin (PFD) is a hexameric chaperone that captures a protein substrate and transfers it to a group II chaperonin (CPN) to complete protein folding. We have studied the interaction between PFD and CPN using those from a hyperthermophilic archaeon, Thermococcus strain KS-1 (T. KS-1). In this study, we determined the crystal structure of the T. KS-1 PFDbeta2 subunit and characterized the interactions between T. KS-1 CPNs (CPNalpha and CPNbeta) and T. KS-1 PFDs (PFDalpha1-beta1 and PFDalpha2-beta2). As predicted from its amino acid sequence, the PFDbeta2 subunit conforms to a structure similar to those of the PFDbeta1 subunit and the Pyrococcus horikoshii OT3 PFDbeta subunit, with the exception of the tip of its coiled-coil domain, which is thought to be the CPN interaction site. The interactions between T. KS-1 CPNs and PFDs (CPNalpha and PFDalpha1-beta1; CPNalpha and PFDalpha2-beta2; CPNbeta and PFDalpha1-beta1; and CPNbeta and PFDalpha2-beta2) were analyzed using the Biacore T100 system at various temperatures ranging from 20 to 45 degrees C. The affinities between PFDs and CPNs increased with an increase in temperature. The thermodynamic parameters calculated from association constants showed that the interaction between PFD and CPN is entropy driven. Among the four combinations of PFD-CPN interactions, the entropy difference in binding between CPNbeta and PFDalpha2-beta2 was the largest, and affinity significantly increased at higher temperatures. Considering that expression of PFDalpha2-beta2 and CPNbeta subunit is induced upon heat shock, our results suggest that PFDalpha1-beta1 is a general PFD for T. KS-1 CPNs, whereas PFDalpha2-beta2 is specific for CPNbeta. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Extrinsic factors regulate partial agonist efficacy of strychnine-sensitive glycine receptors.

PubMed

Farroni, Jeffrey S; McCool, Brian A

2004-08-09

Strychnine-sensitive glycine receptors in many adult forebrain regions consist of alpha2 + beta heteromeric channels. This subunit composition is distinct from the alpha1 + beta channels found throughout the adult spinal cord. Unfortunately, the pharmacology of forebrain alpha2beta receptors are poorly defined compared to 'neonatal' alpha2 homomeric channels or 'spinal' alpha1beta heteromers. In addition, the pharmacologic properties of native alpha2beta glycine receptors have been generally distinct from receptors produced by heterologous expression. To identify subtype-specific pharmacologic tools for the forebrain alpha2beta receptors, it is important to identify a heterologous expression system that closely resembles these native glycine-gated chloride channels. While exploring pharmacological properties of alpha2beta glycine receptors compared to alpha2-homomers, we found that distinct heterologous expression systems appeared to differentially influence partial agonist pharmacology. The beta-amino acid taurine possessed 30-50% efficacy for alpha2-containing receptor isoforms when expressed in HEK 293 cells. However, taurine efficacy was dramatically reduced in L-cell fibroblasts. Similar results were obtained for beta-alanine. The efficacy of these partial agonists was also strongly reduced by the beta subunit. There were no significant differences in apparent strychnine affinity values calculated from concentration-response data between expression systems or subunit combinations. Nor did relative levels of expression correlate with partial agonist efficacy when compared within or between several different expression systems. Finally, disruption of the tubulin cytoskeleton reduced the efficacy of partial agonists in a subunit-dependent, but system-independent, fashion. Our results suggest that different heterologous expression systems can dramatically influence the agonist pharmacology of strychnine-sensitive glycine receptors. In the systems examine here, these effects are independent of both absolute expression level and any system-related alterations in the agonist binding site. We conclude that complex interactions between receptor composition and extrinsic factors may play a significant role in determining strychnine-sensitive glycine receptor partial agonist pharmacology.

Beta-blocker usage after malignant melanoma diagnosis and survival: a population-based nested case-control study.

PubMed

McCourt, C; Coleman, H G; Murray, L J; Cantwell, M M; Dolan, O; Powe, D G; Cardwell, C R

2014-04-01

Beta-blockers have potential antiangiogenic and antimigratory activity. Studies have demonstrated a survival benefit in patients with malignant melanoma treated with beta-blockers. To investigate the association between postdiagnostic beta-blocker usage and risk of melanoma-specific mortality in a population-based cohort of patients with malignant melanoma. Patients with incident malignant melanoma diagnosed between 1998 and 2010 were identified within the U.K. Clinical Practice Research Datalink and confirmed using cancer registry data. Patients with malignant melanoma with a melanoma-specific death (cases) recorded by the Office of National Statistics were matched on year of diagnosis, age and sex to four malignant melanoma controls (who lived at least as long after diagnosis as their matched case). A nested case-control approach was used to investigate the association between postdiagnostic beta-blocker usage and melanoma-specific death and all-cause mortality. Conditional logistic regression was applied to generate odds ratios (ORs) and 95% confidence intervals (CIs) for beta-blocker use determined from general practitioner prescribing. Beta-blocker medications were prescribed after malignant melanoma diagnosis to 20·2% of 242 patients who died from malignant melanoma (cases) and 20·3% of 886 matched controls. Consequently, there was no association between beta-blocker use postdiagnosis and cancer-specific death (OR 0·99, 95% CI 0·68-1·42), which did not markedly alter after adjustment for confounders including stage (OR 0·87, 95% CI 0·56-1·34). No significant associations were detected for individual beta-blocker types, by defined daily doses of use or for all-cause mortality. Contrary to some previous studies, beta-blocker use after malignant melanoma diagnosis was not associated with reduced risk of death from melanoma in this U.K. population-based study. © 2014 British Association of Dermatologists.

Insomnia is Associated with Cortical Hyperarousal as Early as Adolescence.

PubMed

Fernandez-Mendoza, Julio; Li, Yun; Vgontzas, Alexandros N; Fang, Jidong; Gaines, Jordan; Calhoun, Susan L; Liao, Duanping; Bixler, Edward O

2016-05-01

To examine whether insomnia is associated with spectral electroencephalographic (EEG) dynamics in the beta (15-35Hz) range during sleep in an adolescent general population sample. A case-control sample of 44 adolescents from the Penn State Child Cohort underwent a 9-h polysomnography, clinical history and physical examination. We examined low-beta (15-25 Hz) and high-beta (25-35 Hz) relative power at central EEG derivations during sleep onset latency (SOL), sleep onset (SO), non-rapid eye movement (NREM) sleep, and wake after sleep onset (WASO). Compared to controls (n = 21), individuals with insomnia (n = 23) showed increased SOL and WASO and decreased sleep duration and efficiency, while no differences in sleep architecture were found. Insomniacs showed increased low-beta and high-beta relative power during SOL, SO, and NREM sleep as compared to controls. High-beta relative power was greater during all sleep and wake states in insomniacs with short sleep duration as compared to individuals with insomnia with normal sleep duration. Adolescent insomnia is associated with increased beta EEG power during sleep, which suggests that cortical hyperarousal is present in individuals with insomnia as early as adolescence. Interestingly, cortical hyperarousal is greatest in individuals with insomnia with short sleep duration and may explain the sleep complaints of those with normal sleep duration. Disturbed cortical networks may be a shared mechanism putting individuals with insomnia at risk of psychiatric disorders. © 2016 Associated Professional Sleep Societies, LLC.

Combined use of calcium-channel and beta-adrenergic blockers for the treatment of chronic stable angina. Rationale, efficacy, and adverse effects.

PubMed

Strauss, W E; Parisi, A F

1988-10-01

During the past decade, the therapy for stable angina pectoris has greatly expanded with the introduction of the calcium-channel blockers. Initially studied as monotherapy, these agents have been regularly used in combination with other antianginal medications, most notably the beta-adrenergic blockers. Although there are pharmacologic rationales for combining these agents, in daily practice, the major impetus for combination therapy is continuing angina during monotherapy. At least one well-conducted double-blind study was done to confirm that diltiazem, verapamil, and nifedipine each can markedly improve both subjective and objective measures of efficacy when used in combination with a beta-blocker. However, individual patient responses are of chief importance. Many persons do better with monotherapy than with combination treatment. The offsetting hemodynamic effects of nifedipine and a beta-blocker generally work well together; however, minor side effects are not infrequent. In the patient with underlying conduction system disease, this combination is clearly preferable. Diltiazem with a beta-blocker is usually well-tolerated, with a low incidence of adverse effects, similar to the experience with diltiazem monotherapy. Verapamil in conjunction with a beta-blocker warrants the greatest concern; approximately 10% to 15% of patients will have significant bradycardia, heart block, hypotension, or congestive failure. When these agents are used concurrently, reduced dosages, especially of the beta-blocker, will likely result in a lower incidence of adverse effects with maintained efficacy.

Successful implementation of perioperative beta-blockade utilizing a multidisciplinary approach.

PubMed

Armanious, Samuel; Wong, David T; Etchells, Edward; Higgins, Patrick; Chung, Frances

2003-02-01

To describe how we implemented a protocol for perioperative beta-blockade in patients with or at risk of coronary artery disease (CAD) undergoing major non-cardiac surgery and to present our results. After institutional approval, from May 1999 to April 2001, patients with surgical and medical indications (CAD as indicated by previous myocardial infarction, typical angina or atypical angina with a positive stress test or at least two risk factors for CAD: age 65 yr, hypertension, smoking, high cholesterol, diabetes mellitus) for perioperative beta-blockade were identified preoperatively by anesthesiology and referred to the General Internal Medicine Service (MED). MED initiated patients on outpatient beta-blockers. The intraoperative anesthetic management was left to the discretion of the anesthesiologist. In the postanesthesia care unit (PACU), patients received iv metoprolol according to hemodynamic criteria. Postoperatively, patients were followed by MED for adverse cardiac events. Sixty-nine patients received perioperative beta-blockade. Preoperatively, 60% were started on metoprolol, 39% on atenolol and 1% on propranolol. In PACU, 42%, 9% and 38% of patients were given iv metoprolol 0, 5 and 10 mg respectively. One patient was given glycopyrrolate in the PACU for bradycardia and none received vasoactive or inotropic agents. Three patients (4.3%) had postoperative cardiac events. With close collaboration between anesthesiologists, internists, PACU nurses and family physicians, a strategy for perioperative beta-blockade was implemented successfully in patients with cardiac risks. Beta-blockade was associated with few side effects and morbidities.

Gonadal Identity in the Absence of Pro-Testis Factor SOX9 and Pro-Ovary Factor Beta-Catenin in Mice1

PubMed Central

Nicol, Barbara; Yao, Humphrey H.-C.

2015-01-01

Sex-reversal cases in humans and genetic models in mice have revealed that the fate of the bipotential gonad hinges upon the balance between pro-testis SOX9 and pro-ovary beta-catenin pathways. Our central query was: if SOX9 and beta-catenin define the gonad's identity, then what do the gonads become when both factors are absent? To answer this question, we developed mouse models that lack either Sox9, beta-catenin, or both in the somatic cells of the fetal gonads and examined the morphological outcomes and transcriptome profiles. In the absence of Sox9 and beta-catenin, both XX and XY gonads progressively lean toward the testis fate, indicating that expression of certain pro-testis genes requires the repression of the beta-catenin pathway, rather than a direct activation by SOX9. We also observed that XY double knockout gonads were more masculinized than their XX counterpart. To identify the genes responsible for the initial events of masculinization and to determine how the genetic context (XX vs. XY) affects this process, we compared the transcriptomes of Sox9/beta-catenin mutant gonads and found that early molecular changes underlying the XY-specific masculinization involve the expression of Sry and 21 SRY direct target genes, such as Sox8 and Cyp26b1. These results imply that when both Sox9 and beta-catenin are absent, Sry is capable of activating other pro-testis genes and drive testis differentiation. Our findings not only provide insight into the mechanism of sex determination, but also identify candidate genes that are potentially involved in disorders of sex development. PMID:26108792

SMURFLite: combining simplified Markov random fields with simulated evolution improves remote homology detection for beta-structural proteins into the twilight zone.

PubMed

Daniels, Noah M; Hosur, Raghavendra; Berger, Bonnie; Cowen, Lenore J

2012-05-01

One of the most successful methods to date for recognizing protein sequences that are evolutionarily related has been profile hidden Markov models (HMMs). However, these models do not capture pairwise statistical preferences of residues that are hydrogen bonded in beta sheets. These dependencies have been partially captured in the HMM setting by simulated evolution in the training phase and can be fully captured by Markov random fields (MRFs). However, the MRFs can be computationally prohibitive when beta strands are interleaved in complex topologies. We introduce SMURFLite, a method that combines both simplified MRFs and simulated evolution to substantially improve remote homology detection for beta structures. Unlike previous MRF-based methods, SMURFLite is computationally feasible on any beta-structural motif. We test SMURFLite on all propeller and barrel folds in the mainly-beta class of the SCOP hierarchy in stringent cross-validation experiments. We show a mean 26% (median 16%) improvement in area under curve (AUC) for beta-structural motif recognition as compared with HMMER (a well-known HMM method) and a mean 33% (median 19%) improvement as compared with RAPTOR (a well-known threading method) and even a mean 18% (median 10%) improvement in AUC over HHPred (a profile-profile HMM method), despite HHpred's use of extensive additional training data. We demonstrate SMURFLite's ability to scale to whole genomes by running a SMURFLite library of 207 beta-structural SCOP superfamilies against the entire genome of Thermotoga maritima, and make over a 100 new fold predictions. Availability and implementaion: A webserver that runs SMURFLite is available at: http://smurf.cs.tufts.edu/smurflite/

Topical Beta-Blockers and Cardiovascular Mortality: Systematic Review and Meta-Analysis with Data from the EPIC-Norfolk Cohort Study

PubMed Central

Pinnock, Claude; Yip, Jennifer L. Y.; Khawaja, Anthony P.; Luben, Robert; Hayat, Shabina; Broadway, David C.; Foster, Paul J.; Khaw, Kay-Tee; Wareham, Nick

2016-01-01

ABSTRACT Purpose: To determine if topical beta-blocker use is associated with increased cardiovascular mortality, particularly among people with self-reported glaucoma. Methods: All participants who participated in the first health check (N = 25,639) of the European Prospective Investigation into Cancer (EPIC) Norfolk cohort (1993–2013) were included in this prospective cohort study, with a median follow-up of 17.0 years. We determined use of topical beta-blockers at baseline through a self-reported questionnaire and prescription check at the first clinical visit. Cardiovascular mortality was ascertained through data linkage with the Office for National Statistics mortality database. Hazard ratios (HRs) were estimated using multivariable Cox regression models. Meta-analysis of the present study’s results together with other identified literature was performed using a random effects model. Results: We did not find an association between the use of topical beta-blockers and cardiovascular mortality (HR 0.93, 95% confidence interval, CI, 0.67–1.30). In the 514 participants with self-reported glaucoma, no association was found between the use of topical beta-blockers and cardiovascular mortality (HR 0.89, 95% CI 0.56–1.40). In the primary meta-analysis of four publications, there was no evidence of an association between the use of topical beta-blockers and cardiovascular mortality (pooled HR estimate 1.10, 95% CI 0.84–1.36). Conclusion: Topical beta-blockers do not appear to be associated with excess cardiovascular mortality. This evidence does not indicate that a change in current practice is warranted, although clinicians should continue to assess individual patients and their cardiovascular risk prior to commencing topical beta-blockers. PMID:27551956

Role for transforming growth factor-beta1 in alport renal disease progression.

PubMed

Sayers, R; Kalluri, R; Rodgers, K D; Shield, C F; Meehan, D T; Cosgrove, D

1999-11-01

Alport syndrome results from mutations in either the alpha3(IV), alpha4(IV), or alpha5(IV) collagen genes. The disease is characterized by a progressive glomerulonephritis usually associated with a high-frequency sensorineural hearing loss. A mouse model for an autosomal form of Alport syndrome [collagen alpha3(IV) knockout] was produced and characterized. In this study, the model was exploited to demonstrate a potential role for transforming growth factor-beta1 (TGF-beta1) in Alport renal disease pathogenesis. Kidneys from normal and Alport mice, taken at different stages during the course of renal disease progression, were analyzed by Northern blot, in situ hybridization, and immunohistology for expression of TGF-beta1 and components of the extracellular matrix. Normal and Alport human kidney was examined for TGF-beta1 expression using RNase protection. The mRNAs encoding TGF-beta1 (in both mouse and human), entactin, fibronectin, and the collagen alpha1(IV) and alpha2(IV) chains were significantly induced in total kidney as a function of Alport renal disease progression. The induction of these specific mRNAs was observed in the glomerular podocytes of animals with advanced disease. Type IV collagen, laminin-1, and fibronectin were markedly elevated in the tubulointerstitium at 10 weeks, but not at 6 weeks, suggesting that elevated expression of specific mRNAs on Northern blots reflects events associated with tubulointerstitial fibrosis. The concomitant accumulation of mRNAs encoding TGF-beta1 and extracellular matrix components in the podocytes of diseased kidneys may reflect key events in Alport renal disease progression. These data suggest a role for TGF-beta1 in both glomerular and tubulointerstitial damage associated with Alport syndrome.

Contrasting species and functional beta diversity in montane ant assemblages.

PubMed

Bishop, Tom R; Robertson, Mark P; van Rensburg, Berndt J; Parr, Catherine L

2015-09-01

Beta diversity describes the variation in species composition between sites and can be used to infer why different species occupy different parts of the globe. It can be viewed in a number of ways. First, it can be partitioned into two distinct patterns: turnover and nestedness. Second, it can be investigated from either a species identity or a functional-trait point of view. We aim to document for the first time how these two aspects of beta diversity vary in response to a large environmental gradient. Maloti-Drakensberg Mountains, southern Africa. We sampled ant assemblages along an extensive elevational gradient (900-3000 m a.s.l.) twice yearly for 7 years, and collected functional-trait information related to the species' dietary and habitat-structure preferences. We used recently developed methods to partition species and functional beta diversity into their turnover and nestedness components. A series of null models were used to test whether the observed beta diversity patterns differed from random expectations. Species beta diversity was driven by turnover, but functional beta diversity was composed of both turnover and nestedness patterns at different parts of the gradient. Null models revealed that deterministic processes were likely to be responsible for the species patterns but that the functional changes were indistinguishable from stochasticity. Different ant species are found with increasing elevation, but they tend to represent an increasingly nested subset of the available functional strategies. This finding is unique and narrows down the list of possible factors that control ant existence across elevation. We conclude that diet and habitat preferences have little role in structuring ant assemblages in montane environments and that some other factor must be driving the non-random patterns of species turnover. This finding also highlights the importance of distinguishing between different kinds of beta diversity.

Relationship of Pain and Ancestry in African American Women

PubMed Central

Robbins, John A.; Qi, Lihong; Garcia, Lorena; Younger, Jarred W.; Seldin, Michael F.

2015-01-01

Background African Americans are reported to be more sensitive to pain than European Americans. Pain sensitivity has been shown to be genetically linked in animal models and is likely to be in humans. Methods 11,239 self-identified African American post menopausal women enrolled in the Women’s Health Initiative had percentage African ancestry determined by ancestry informative markers, “Pain Construct” measurements and covariate information. They answered 5 questions about specific types and location of pain, such as joint, neck, low back, headache, and urinary. They also answered 2 questions which were used to derive a “Pain Construct”, a measure of general pain scored on a scale of 1 to 100. Associations were tested in linear regression models adjusting for age, self-reported medical conditions, neighborhood socio-economic status, education, and depression. Results In the unadjusted model of the 5 specific types of pain measures, greater pain perception was associated with a higher proportion of African ancestry. However, some of the specific types of pain measures were no longer associated with African ancestry after adjustment for other study covariates. The Pain Construct was statistically significantly associated with African ancestry in both the unadjusted [Beta = −0.132, 95% confidence interval (C I) = −099 – −0.164; r = −0.075, 95% CI −0.056 – −0.093] and the adjusted models (Beta = −0.069 95% CI = −0.04 – 0.10). Conclusions Greater African ancestry was associated with higher levels of self-reported pain although this accounted for only a minor fraction of the overall variation in the Pain Construct. PMID:25752262

Exact near-onset analysis of the spin-density-wave instability in ferromagnetic superconductors: The linearly polarized state

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hu, C.

1984-09-01

Using an approach similar to Abvikosov's theory of the vortex state near H/sub c/2, we have performed an exact, near-onset analysis of a spin-density-wave instability leading to the ''linearly polarized state'' of Greenside et al. in ferromagnetic superconductors. The approach is based on a generalized Ginzburg-Landau theory for such materials, as formulated by Blount and Varma. Two models have been considered. In the (..cap alpha..,..beta..) model, where the bulk magnetic energy is taken to be (1/2)..cap alpha../sub m/M/sup 2/+(1/4)..beta../sub m/M/sup 4/, we find the transition to be second order, and obtain explicit formulas for various physical quantities to leading ordermore » in the deviation from onset. We have also rigorously analyzed the most favored spatial structure just below onset, among all possibilities allowed by the instability, and have concluded that a plane-wave-like structure is favored in a physical limit considered. In the (..cap alpha..,..gamma..) model, where the bulk magnetic energy is taken to be (1/2)..cap alpha../sub m/M/sup 2/+(1/6)..gamma../sub m/M/sup 6/ as is supported by recent experiments for ErRh/sub 4/B/sub 4/, we find the transition to be first order. This approach is then confined to an unphysical branch, which does not permit us to calculate various physical quantities on the physical branch.« less