Affinity modulation of platelet integrin alphaIIbbeta3 by beta3-endonexin, a selective binding partner of the beta3 integrin cytoplasmic tail.

Platelet agonists increase the affinity state of integrin alphaIIbbeta3, a prerequisite for fibrinogen binding and platelet aggregation. This process may be triggered by a regulatory molecule(s) that binds to the integrin cytoplasmic tails, causing a structural change in the receptor. beta3-Endonexin is a novel 111-amino acid protein that binds selectively to the beta3 tail. Since beta3-endonexin is present in platelets, we asked whether it can affect alphaIIbbeta3 function. When beta3-endonexin was fused to green fluorescent protein (GFP) and transfected into CHO cells, it was found in both the cytoplasm and the nucleus and could be detected on Western blots of cell lysates. PAC1, a fibrinogen-mimetic mAb, was used to monitor alphaIIbbeta3 affinity state in transfected cells by flow cytometry. Cells transfected with GFP and alphaIIbbeta3 bound little or no PAC1. However, those transfected with GFP/beta3-endonexin and alphaIIbbeta3 bound PAC1 specifically in an energy-dependent fashion, and they underwent fibrinogen-dependent aggregation. GFP/beta3-endonexin did not affect levels of surface expression of alphaIIbbeta3 nor did it modulate the affinity of an alphaIIbbeta3 mutant that is defective in binding to beta3-endonexin. Affinity modulation of alphaIIbbeta3 by GFP/beta3-endonexin was inhibited by coexpression of either a monomeric beta3 cytoplasmic tail chimera or an activated form of H-Ras. These results demonstrate that beta3-endonexin can modulate the affinity state of alphaIIbbeta3 in a manner that is structurally specific and subject to metabolic regulation. By analogy, the adhesive function of platelets may be regulated by such protein-protein interactions at the level of the cytoplasmic tails of alphaIIbbeta3

Spread of Infectious Diseases with a Latent Period

Infectious diseases spread through human networks. Susceptible-Infected-Removed (SIR) model is one of the epidemic models to describe infection dynamics on a complex network connecting individuals. In the metapopulation SIR model, each node represents a population (group) which has many individuals. In this paper, we propose a modified metapopulation SIR model in which a latent period is taken into account. We call it SIIR model. We divide the infection period into two stages: an infected stage, which is the same as the previous model, and a seriously ill stage, in which individuals are infected and cannot move to the other populations. The two infectious stages in our modified metapopulation SIR model produce a discontinuous final size distribution. Individuals in the infected stage spread the disease like individuals in the seriously ill stage and never recover directly, which makes an effective recovery rate smaller than the given recovery rate.Comment: 6 pages, 3 figure

Existence and approximation of Hunt processes associated with generalized Dirichlet forms

We show that any strictly quasi-regular generalized Dirichlet form that satisfies the mild structural condition D3 is associated to a Hunt process, and that the associated Hunt process can be approximated by a sequence of multivariate Poisson processes. This also gives a new proof for the existence of a Hunt process associated to a strictly quasi-regular generalized Dirichlet form that satisfies SD3 and extends all previous results.Comment: Revised, shortened and improved versio

gem-Dibromocyclopropanes and enzymatically derived cis-1,2-dihydrocatechols as building blocks in alkaloid synthesis

The application of the title building blocks, the 6,6-dibromobicyclo[3.1.0]hexanes and the cis-1,2-dihydrocatechols, to the total synthesis of crinine and lycorinine alkaloids is described.We thank the Australian Research Council and the Institute of Advanced Studies for generous financial support

Discovery of Quasi-Periodic Oscillations in the Recurrent Burst Emission from SGR 1806-20

We present evidence for Quasi-Periodic Oscillations (QPOs) in the recurrent outburst emission from the soft gamma repeater SGR 1806-20 using NASA's Rossi X-ray Timing Explorer (RXTE) observations. By searching a sample of 30 bursts for timing signals at the frequencies of the QPOs discovered in the 2004 December 27 giant flare from the source, we find three QPOs at 84, 103, and 648 Hz in three different bursts. The first two QPOs lie within $\sim$ 1$\: \sigma$ from the 92 Hz QPO detected in the giant flare. The third QPO lie within $\sim$ 9$\: \sigma$ from the 625 Hz QPO also detected in the same flare. The detected QPOs are found in bursts with different durations, morphologies, and brightness, and are vindicated by Monte Carlo simulations, which set a lower limit confidence interval $\geq 4.3 \sigma$. We also find evidence for candidate QPOs at higher frequencies in other bursts with lower statistical significance. The fact that we can find evidence for QPOs in the recurrent bursts at frequencies relatively close to those found in the giant flare is intriguing and can offer insight about the origin of the oscillations. We confront our finding against the available theoretical models and discuss the connection between the QPOs we report and those detected in the giant flares. The implications to the neutron star properties are also discussed.Comment: 5 pages, 2 figures, Accepted for publication in the Astrophysical Journal Letters (ApJL

Impact of Community Outreach Reflection

My time as the Co-President for the Student Community Outreach for Public Education, or SCOPE, has been instrumental in my dental school experience. Our goal is to empower students as dental educators within their community. SCOPE provides disease prevention, oral health education, screening and preventative dental services to underserved members of the San Francisco Bay Area. Not only are we aiming to support those in our community, but we are empowering students as they grow to become effective dental educators and providers. Community outreach is extremely important in dental school education as it allows students to engage with their local community and understand the impact their education has beyond the four walls of school. To determine the effectiveness of community outreach in students’ experiences, it is essential that students submit reflections on their experiences. Dental schools are aware of the ways in which volunteerism can have a profound effect on students’ empathy which can greatly influence their treatment of patients. Written reflections can help the students examine the positive effect of working in the community, and also provide the administration with a summary of each student’s experience. There is limited research on the impact of reflective writing on dental student empathy levels. This paper aims to gather reflective data from dental students and evaluate the impact community health has had on their dental school career

Impact of Community Outreach Reflection

My time as the Co-President for the Student Community Outreach for Public Education, or SCOPE, has been instrumental in my dental school experience. Our goal is to empower students as dental educators within their community. SCOPE provides disease prevention, oral health education, screening and preventative dental services to underserved members of the San Francisco Bay Area. Not only are we aiming to support those in our community, but we are empowering students as they grow to become effective dental educators and providers. Community outreach is extremely important in dental school education as it allows students to engage with their local community and understand the impact their education has beyond the four walls of school. To determine the effectiveness of community outreach in students’ experiences, it is essential that students submit reflections on their experiences. Dental schools are aware of the ways in which volunteerism can have a profound effect on students’ empathy which can greatly influence their treatment of patients. Written reflections can help the students examine the positive effect of working in the community, and also provide the administration with a summary of each student’s experience. There is limited research on the impact of reflective writing on dental student empathy levels. This paper aims to gather reflective data from dental students and evaluate the impact community health has had on their dental school career

Climatic change controls productivity variation in global grasslands.

Detection and identification of the impacts of climate change on ecosystems have been core issues in climate change research in recent years. In this study, we compared average annual values of the normalized difference vegetation index (NDVI) with theoretical net primary productivity (NPP) values based on temperature and precipitation to determine the effect of historic climate change on global grassland productivity from 1982 to 2011. Comparison of trends in actual productivity (NDVI) with climate-induced potential productivity showed that the trends in average productivity in nearly 40% of global grassland areas have been significantly affected by climate change. The contribution of climate change to variability in grassland productivity was 15.2-71.2% during 1982-2011. Climate change contributed significantly to long-term trends in grassland productivity mainly in North America, central Eurasia, central Africa, and Oceania; these regions will be more sensitive to future climate change impacts. The impacts of climate change on variability in grassland productivity were greater in the Western Hemisphere than the Eastern Hemisphere. Confirmation of the observed trends requires long-term controlled experiments and multi-model ensembles to reduce uncertainties and explain mechanisms

Coupling between gamma-band power and cerebral blood volume during recurrent acute neocortical seizures

Characterization of neural and hemodynamic biomarkers of epileptic activity that can be measured using non-invasive techniques is fundamental to the accurate identification of the epileptogenic zone (EZ) in the clinical setting. Recently, oscillations at gamma-band frequencies and above (>30 Hz) have been suggested to provide valuable localizing information of the EZ and track cortical activation associated with epileptogenic processes. Although a tight coupling between gamma-band activity and hemodynamic-based signals has been consistently demonstrated in non-pathological conditions, very little is known about whether such a relationship is maintained in epilepsy and the laminar etiology of these signals. Confirmation of this relationship may elucidate the underpinnings of perfusion-based signals in epilepsy and the potential value of localizing the EZ using hemodynamic correlates of pathological rhythms. Here, we use concurrent multi-depth electrophysiology and 2-dimensional optical imaging spectroscopy to examine the coupling between multi-band neural activity and cerebral blood volume (CBV) during recurrent acute focal neocortical seizures in the urethane-anesthetized rat. We show a powerful correlation between gamma-band power (25-90 Hz) and CBV across cortical laminae, in particular layer 5, and a close association between gamma measures and multi-unit activity (MUA). Our findings provide insights into the laminar electrophysiological basis of perfusion-based imaging signals in the epileptic state and may have implications for further research using non-invasive multi-modal techniques to localize epileptogenic tissue