Progress Towards Integrated Models of HCV Dynamics

Hepatitis C virus is a small, enveloped positiveâ€strand RNA member of the Flaviviridae and the etiological agent of a global epidemic of chronic hepatitis C. One of the salient features of HCV is a complex regulatory scheme involving numerous viral and cellular components and which may be the key to its striking success in initiating and maintaining decadesâ€long chronic disease in infected individuals. Lacking any known latent or integrated form, HCV must persist through ongoing RNA replication, immune evasion, and infection of naïve cells. HCV is a highlyâ€studied virus, and many details of its life cycle have been worked out; however, much remains unknown. One thing lacking is an integrated model of HCV as a single dynamic system. Various viral life cycle events, such as entry, polyprotein translation and processing, RNA replication, virion morphogenesis and secretion have been studied and worked out to some extent. How these activities are coordinated and how they influence each other is less wellunderstood. We approached this problem from three angles. We developed quantitative mathematical models designed to accurately recapitulate the specific processes of virus production and accumulation and virus entry. These models were applied to gain a more detailed understanding of these systems. We studied the HCV regulatory protein NS5A through genetic and chemical perturbation to try to understand how it might be connecting different life cycle activities. These studies revealed a surprising role for the host cellular protein cyclophilin A in regulating virus assembly as well as clarifying aspects of NS5A phosphorylation. These findings suggest a complex system of regulation linking polyprotein translation, RNA replication, and virion assembly which will require further work to decipher. We also pursued a bioinformatics approach, in which we analyzed HCV multiple sequence alignments (MSAs) to identify covariant amino acid positions within HCV proteins. Some of the challenges to the study of covariation in HCV MSAs were identified, and we describe a novel method of calculating covariation which addresses some of these issues, particularly the problem of phylogenetic covariance. While an integrated dynamic model of HCV remains far from achieved, these studies are presented as incremental steps towards that goal

Plasma 2020 - Intracluster Medium Plasmas

Galaxy clusters are the largest and most massive bound objects resulting from cosmic hierarchical structure formation. Baryons account for somewhat more than 10% of that mass, with roughly 90% of the baryonic matter distributed throughout the clusters as hot ($T>1$ keV), high-$\beta$, very weakly collisional plasma; the so-called "intracluster medium" (ICM). Cluster mergers, close gravitational encounters and accretion, along with violent feedback from galaxies and relativistic jets from active galactic nuclei, drive winds, gravity waves, turbulence and shocks within the ICM. Those dynamics, in turn, generate cluster-scale magnetic fields and accelerate and mediate the transport of high-energy charged particles. Kinetic-scale, collective plasma processes define the basic character and fundamental signatures of these ICM phenomena, which are observed primarily by X-ray and radio astronomers.Comment: 5 pages, 2 figures, submitted for the 2020 Decadal Assessment of Plasma Scienc

The importance of race in medical student performance of an AIDS risk assessment interview with simulated patients

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75349/1/j.1365-2923.2000.00455.x.pd

Characterization of anisotropic nano-particles by using depolarized dynamic light scattering in the near field

Light scattering techniques are widely used in many fields of condensed and sof t matter physics. Usually these methods are based on the study of the scattered light in the far field. Recently, a new family of near field detection schemes has been developed, mainly for the study of small angle light scattering. These techniques are based on the detection of the light intensity near to the sample, where light scattered at different directions overlaps but can be distinguished by Fourier transform analysis. Here we report for the first time data obtained with a dynamic near field scattering instrument, measuring both polarized and depolarized scattered light. Advantages of this procedure over the traditional far field detection include the immunity to stray light problems and the possibility to obtain a large number of statistical samples for many different wave vectors in a single instantaneous measurement. By using the proposed technique we have measured the translational and rotational diffusion coefficients of rod-like colloidal particles. The obtained data are in very good agreement with the data acquired with a traditional light scattering apparatus.Comment: Published in Optics Express. This version has changes in bibliograph

A Naturally Narrow Positive Parity Theta^+

We present a consistent color-flavor-spin-orbital wave function for a positive parity Theta^+ that naturally explains the observed narrowness of the state. The wave function is totally symmetric in its flavor-spin part and totally antisymmetric in its color-orbital part. If flavor-spin interactions dominate, this wave function renders the positive parity Theta^+ lighter than its negative parity counterpart. We consider decays of the Theta^+ and compute the overlap of this state with the kinematically allowed final states. Our results are numerically small. We note that dynamical correlations between quarks are not necessary to obtain narrow pentaquark widths.Comment: 10 pages, 1 figure, Revtex4, two-column format, version to be published in Phys. Rev. D, includes numerical estimates of decay width

Clinical, microbiological, and salivary biomarker profiles of dental implant patients with type 2 diabetes

Objective Regulators of peri‐implant bone loss in patients with diabetes appear to involve multiple risk factors that have not been clearly elucidated. This study was conducted to explore putative local etiologic factors on implant bone loss in relation to type 2 diabetes mellitus, including clinical, microbial, salivary biomarker, and psychosocial factors. Materials and methods Thirty‐two subjects (divided into type 2 diabetes mellitus and non‐diabetic controls), having at least one functional implant and six teeth, were enrolled in a 1‐year longitudinal investigation. Analyses of clinical measurements and standardized intra‐oral radiographs, saliva and serum biomarkers (via protein arrays for 20 selected markers), and plaque biofilm (via q PCR for eight periodontal pathogens) were performed at baseline and 1 year. In addition, the subjects were asked to respond to questionnaires to assess behavioral and psychosocial variables. Results There was a significant increase from baseline to 1 year in the probing depth of implants in the diabetes group (1.95 mm to 2.35 mm, P  = 0.015). The average radiographic bone loss during the study period marginally increased at dental implants compared to natural teeth over the study period (0.08 mm vs. 0.05 mm; P  = 0.043). The control group harbored higher levels of T reponema denticola at their teeth at baseline ( P  = 0.046), and the levels of the pathogen increased significantly over time around the implants of the same group ( P  = 0.003). Salivary osteoprotegerin ( OPG ) levels were higher in the diabetes group than the control group at baseline only; in addition, the salivary levels of IL ‐4, IL ‐10, and OPG associated with host defense were significantly reduced in the diabetes group ( P  = 0.010, P  = 0.019, and P  = 0.024), while controls showed an increase in the salivary OPG levels ( P  = 0.005). For psychosocial factors, there were not many significant changes over the observation period, except for some findings related to coping behaviors at baseline. Conclusions The study suggests that the clinical, microbiological, salivary biomarker, and psychosocial profiles of dental implant patients with type 2 diabetes who are under good metabolic control and regular maintenance care are very similar to those of non‐diabetic individuals. Future studies are warranted to validate the findings in longer‐term and larger clinical trials ( ClinicalTrials.gov # NCT00933491).Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/107497/1/clr12139.pd

First hint for CP violation in neutrino oscillations from upcoming superbeam and reactor experiments

We compare the physics potential of the upcoming neutrino oscillation experiments Daya Bay, Double Chooz, NOvA, RENO, and T2K based on their anticipated nominal luminosities and schedules. After discussing the sensitivity to theta_{13} and the leading atmospheric parameters, we demonstrate that leptonic CP violation will hardly be measurable without upgrades of the T2K and NOvA proton drivers, even if theta_{13} is large. In the presence of the proton drivers, the fast track to hints for CP violation requires communication between the T2K and NOvA collaborations in terms of a mutual synchronization of their neutrino-antineutrino run plans. Even in that case, upgrades will only discover CP violation in a relatively small part of the parameter space at the 3 sigma confidence level, while 90% confidence level hints will most likely be obtained. Therefore, we conclude that a new facility will be required if the goal is to obtain a significant result with high probability.Comment: 27 pages, 12 figure

An ATP-binding cassette-type cysteine transporter in Campylobacter jejuni inferred from the structure of an extracytoplasmic solute receptor protein

Campylobacter jejuni is a Gram-negative food-borne pathogen associated with gastroenteritis in humans as well as cases of the autoimmune disease Guillain Barre syndrome. C. jejuni is asaccharolytic because it lacks an active glycolytic pathway for the use of sugars as a carbon source. This suggests an increased reliance on amino acids as nutrients and indeed the genome sequence of this organism indicates the presence of a number of amino acid uptake systems. Cj0982, also known as CjaA, is a putative extracytoplasmic solute receptor for one such uptake system as well as a major surface antigen and vaccine candidate. The crystal structure of Cj0982 reveals a two-domain protein with density in the enclosed cavity between the domains that clearly defines the presence of a bound cysteine ligand. Fluorescence titration experiments were used to demonstrate that Cj0982 binds cysteine tightly and specifically with a K-d of similar to 10(-7) M consistent with a role as a receptor for a high- affinity transporter. These data imply that Cj0982 is the binding protein component of an ABC-type cysteine transporter system and that cysteine uptake is important in the physiology of C. jejuni