Kinetics of acute hepatitis B virus infection in humans

Using patient data from a unique single source outbreak of hepatitis B virus (HBV) infection, we have characterized the kinetics of acute HBV infection by monitoring viral turnover in the serum during the late incubation and clinical phases of the disease in humans. HBV replicates rapidly with minimally estimated doubling times ranging between 2.2 and 5.8 d (mean 3.7 ± 1.5 d). After a peak viral load in serum of nearly 1010 HBV DNA copies/ml is attained, clearance of HBV DNA follows a two or three phase decay pattern with an initial rapid decline characterized by mean half-life (t1/2) of 3.7 ± 1.2 d, similar to the t1/2 observed in the noncytolytic clearance of covalently closed circular DNA for other hepadnaviruses. The final phase of virion clearance occurs at a variable rate (t1/2 of 4.8 to 284 d) and may relate to the rate of loss of infected hepatocytes. Free virus has a mean t1/2 of at most 1.2 ± 0.6 d. We estimate a peak HBV production rate of at least 1013 virions/day and a maximum production rate of an infected hepatocyte of 200–1,000 virions/day, on average. At this peak rate of virion production we estimate that every possible single and most double mutations would be created each day

Aggregations of the sandy-beach isopod, Tylos granulatus: adaptation or incidental-effect?

Spatial aggregations of organisms are common in nature. Aggregations have often been thought to play important roles in mate-finding, predator avoidance, reduction of water loss, or the acquisition of food and other resources, yet few empirical studies have been done on the processes that lead to aggregation We studied aggregations of the giant isopod Tylos granulatus, which lives as a scavenger in the intertidal zone of sandy beaches on the west coast of South Africa. Individuals emerge with the receding tide leaving exit holes, then forage for about two hours before returning to the vicinity of the high-water mark where they aggregate to bury themselves, leaving behind cone-shaped mounds. Our observations showed there was no correlation between aggregations and the availability of food, and that manipulating the position of food had no effect on the aggregations. Reproduction, which is seasonal and synchronous, also seems unlikely to explain the year-round aggregations. Experiments showed T. granulatus preferentially burrows in existing holes or mounds rather than creating new ones. The advantages of this are analysed in terms of energy conservation, and as a means of reducing risks of exposure to predators or being swept away by the incoming tide. Whatever the benefit, the preferential use of existing holes can incidentally lead to aggregation, which may not itself have any adaptive function

Properties of visual field defects around the monocular preferred retinal locus in age-related macular degeneration

YesPURPOSE. To compare microperimetric sensitivity around the monocular preferred retinal locus (mPRL) in age-related macular degeneration (AMD) to normative data, and to describe the characteristics of visual field defects around the mPRL in AMD. METHODS. Participants with AMD (total n ¼ 185) were either prospectively recruited (n ¼ 135) or retrospectively reviewed from an existing database (n ¼ 50). Participants underwent microperimetry using a test pattern (37 point, 58 radius) centered on their mPRL. Sensitivities were compared to normative data by spatial interpolation, and conventional perimetric indices were calculated. The location of the mPRL relative to the fovea and to visual field defects was also investigated. RESULTS. Location of mPRL varied approximately 158 horizontally and vertically. Visual field loss within 58 of the mPRL was considerable in the majority of participants (median mean deviation 14.7 dB, interquartile range [IQR] 19.6 to 9.6 dB, median pattern standard deviation 7.1 dB [IQR 4.8–9.0 dB]). Over 95% of participants had mean total deviation worse than 2 dB across all tested locations and similarly within 18 of their mPRL. A common pattern of placing the mPRL just foveal to a region of normal pattern deviation was found in 78% of participants. Total deviation was outside normal limits in this region in 68%. CONCLUSIONS. Despite altering fixation to improve vision, people with AMD exhibit considerable visual field loss at and around their mPRL. The location of the mPRL was typically just foveal to, but not within, a region of relatively normal sensitivity for the individual, suggesting that a combination of factors drives mPRL selection.This report presents independent research funded by the NIH

Sydnone Cycloaddition Route to Pyrazole-Based Analogs of Combretastatin A4.

The combretastatins are an important class of tubulin-binding agents. Of this family, a number of compounds are potent tumor Vascular Disrupting Agents (VDAs) and have shown promise in the clinic for cancer therapy. We have developed a modular synthetic route to combretastatin analogs based on a pyrazole core through highly-regioselective alkyne cycloaddition reactions of sydnones. These compounds show modest to high potency against human umbilical vein endothelial cell proliferation. Moreover, evidence is presented that these novel VDAs have the same mode of action as CA4P and bind reversibly to β-tubulin - believed to be a key feature in avoiding toxicity. The most active compound from in vitro studies was taken forward to an in vivo model and instigated an increase in tumor cell necrosis

Non-Markovian Decay of a Three Level Cascade Atom in a Structured Reservoir

We present a formalism that enables the study of the non-Markovian dynamics of a three-level ladder system in a single structured reservoir. The three-level system is strongly coupled to a bath of reservoir modes and two quantum excitations of the reservoir are expected. We show that the dynamics only depends on reservoir structure functions, which are products of the mode density with the coupling constant squared. This result may enable pseudomode theory to treat multiple excitations of a structured reservoir. The treatment uses Laplace transforms and an elimination of variables to obtain a formal solution. This can be evaluated numerically (with the help of a numerical inverse Laplace transform) and an example is given. We also compare this result with the case where the two transitions are coupled to two separate structured reservoirs (where the example case is also analytically solvable)

ρ\rho-mass Modification in He3He^3 - a Signal of Restoration of Chiral Symmetry or Test for Nuclear Matter Models ?

Two recent experiments have demonstrated that the effective $\rho$-mass in nuclear medium, as extracted from the $^3He(\gamma, \pi^+ \pi^-)$ reaction, is substantially reduced. This has been advocated as an indication of partial restoration of chiral symmetry in nuclear matter. We show that even in the absence of chiral symmetry, effective mean field nuclear matter models can explain these findings quantitatively.Comment: ReVTeX file with 2 postscript figures include

New Massive Gravity Domain Walls

The properties of the asymptotic $AdS_3$ space-times representing flat domain walls (DW's) solutions of the New Massive 3D Gravity with scalar matter are studied. Our analysis is based on $I^{st}$ order BPS-like equations involving an appropriate superpotential. The Brown-York boundary stress-tensor is used for the calculation of DW's tensions as well as of the $CFT_2$'s central charges. The holographic renormalization group flows and the phase transitions in specific deformed $CFT_2$ dual to 3D massive gravity model with quadratic superpotential are discussed.Comment: 12 pages,v2-misprints corrected,comments concerning BPS eqs. for NMG model in d>3 added in Sect.

The mixed problem in L^p for some two-dimensional Lipschitz domains

We consider the mixed problem for the Laplace operator in a class of Lipschitz graph domains in two dimensions with Lipschitz constant at most 1. The boundary of the domain is decomposed into two disjoint sets D and N. We suppose the Dirichlet data, f_D has one derivative in L^p(D) of the boundary and the Neumann data is in L^p(N). We find conditions on the domain and the sets D and N so that there is a p_0>1 so that for p in the interval (1,p_0), we may find a unique solution to the mixed problem and the gradient of the solution lies in L^p

Anomalous specific heat in high-density QED and QCD

Long-range quasi-static gauge-boson interactions lead to anomalous (non-Fermi-liquid) behavior of the specific heat in the low-temperature limit of an electron or quark gas with a leading $T\ln T^{-1}$ term. We obtain perturbative results beyond the leading log approximation and find that dynamical screening gives rise to a low-temperature series involving also anomalous fractional powers $T^{(3+2n)/3}$. We determine their coefficients in perturbation theory up to and including order $T^{7/3}$ and compare with exact numerical results obtained in the large-$N_f$ limit of QED and QCD.Comment: REVTEX4, 6 pages, 2 figures; v2: minor improvements, references added; v3: factor of 2 error in the T^(7/3) coefficient corrected and plots update