Epidemiology and strain characterization of rotavirus diarrhea in Malaysia

SummaryObjectivesThe objectives of the study were to describe the epidemiology and strain characterization of rotavirus (RV), to determine the proportion of hospitalizations for diarrhea attributable to RV among children under 5 years of age, and to estimate the disease burden of RV diarrhea in Malaysia.MethodsAll children 0–59 months of age admitted for acute gastroenteritis to Kuala Lumpur Hospital (KLH) or Hospital Umum Sarawak (HUS) were surveyed. The periods of surveillance were from February 1, 2001 to April 30, 2003 in KLH and April 1, 2001 to March 31, 2003 for HUS.ResultsThe highest rate of RV-associated diarrhea was among children aged 6–17 months, accounting for 55% of RV-associated diarrhea. There was no seasonality observed in either hospital. P[8]G9 strains were predominant, accounting for 73% of all strains in both hospitals, 80% from KLH and 61% from HUS. There was no mortality.ConclusionsRV was responsible for 38% of hospitalizations for diarrhea. It was most common in the 6–17 months age group. There was no seasonality observed for RV-associated diarrhea. The most prevalent strain of RV was P[8]G9. The estimated incidence of RV-associated diarrhea was 27 per 10000 population under the age of 5 years per year

Influence of decreasing nutrient path length on the development of engineered cartilage

SummaryObjectiveChondrocyte-seeded agarose constructs of 4mm diameter (2.34mm thickness) develop spatially inhomogeneous material properties with stiffer outer edges and a softer central core suggesting nutrient diffusion limitations to the central construct region [Guilak F, Sah RL, Setton LA. Physical regulation of cartilage metabolism. In: Mow VC, Hayes WC, Eds. Basic Orthopaedic Biomechanics, Philadelphia 1997;179–207.]. The effects of reducing construct thickness and creating channels running through the depth of the thick constructs were examined.MethodsIn Study 1, the properties of engineered cartilage of 0.78mm (thin) or 2.34mm (thick) thickness were compared. In Study 2, a single nutrient channel (1mm diameter) was created in the middle of each thick construct. In Study 3, the effects of channels on larger 10mm diameter, thick constructs were examined.ResultsThin constructs developed superior mechanical and biochemical properties than thick constructs. The channeled constructs developed significantly higher mechanical properties vs control channel-free constructs while exhibiting similar glycosaminoglycan (GAG) and collagen content. Collagen staining suggested that channels resulted in a more uniform fibrillar network. Improvements in constructs of 10mm diameter were similarly observed.ConclusionsThis study demonstrated that more homogeneous tissue-engineered cartilage constructs with improved mechanical properties can be achieved by reducing their thickness or incorporating macroscopic nutrient channels. Our data further suggests that these macroscopic channels remain open long enough to promote this enhanced tissue development while exhibiting the potential to refill with cell elaborated matrix with additional culture time. Together with reports that <3mm defects in cartilage heal in vivo and that irregular holes are associated with clinically used osteochondral graft procedures, we anticipate that a strategy of incorporating macroscopic channels may aid the development of clinically relevant engineered cartilage with functional properties

The phase diagram of the extended anisotropic ferromagnetic-antiferromagnetic Heisenberg chain

By using Density Matrix Renormalization Group (DMRG) technique we study the phase diagram of 1D extended anisotropic Heisenberg model with ferromagnetic nearest-neighbor and antiferromagnetic next-nearest-neighbor interactions. We analyze the static correlation functions for the spin operators both in- and out-of-plane and classify the zero-temperature phases by the range of their correlations. On clusters of $64,100,200,300$ sites with open boundary conditions we isolate the boundary effects and make finite-size scaling of our results. Apart from the ferromagnetic phase, we identify two gapless spin-fluid phases and two ones with massive excitations. Based on our phase diagram and on estimates for the coupling constants known from literature, we classify the ground states of several edge-sharing materials.Comment: 12 pages, 13 figure

Catalytic Ammonia Decomposition for Coal-Derived Fuel Gases

The objective of this study is to develop and demonstrate catalytic approaches for decomposing a significant percentage (up to 90 percent) of the NH{sub 3} present in fuel gas to N{sub 2} and H{sub 2} at elevated temperatures (550 to 900{degrees}C). The NH{sub 3} concentration considered in this study was {similar_to}1,800 to 2,000 ppmv, which is typical of oxygen-blown, entrained-flow gasifiers such as the Texaco coal gasifier being employed at the TECO Clean Coal Technology Demonstration plant. Catalysts containing Ni, Co, Mo, and W were candidates for the study. Before undertaking any experiments, a detailed thermodynamic evaluation was conducted to determine the concentration of NH{sub 3} in equilibrium with the Texaco gasifier coal gas. Thermodynamic evaluations were also performed to evaluate the stability of the catalytic phases (for the various catalysts under consideration) under NH3 decomposition conditions to be used in this study. Two catalytic approaches for decomposing NH{sub 3} have been experimentally evaluated. The first approach evaluated during the early phases of this project involved the screening of catalysts that could be combined with the hot-gas desulfurization sorbents (e.g., zinc titanate) for simultaneous NH{sub 3} and H{sub 2}S removal. In a commercial system, this approach would reduce capital costs by eliminating a process step. The second approach evaluated was high-temperature catalytic decomposition at 800 to 900{degrees} C. In a commercial hot-gas cleanup system this could be carried out after radiative cooling of the gas to 800 to 900{degrees}C but up stream of the convective cooler, the hot particulate filter, and the hot-gas desulfurization reactor. Both approaches were tested in the presence of up to 7,500 ppmv H{sub 2}S in simulated fuel gas or actual fuel gas from a coal gasifier

Minimal Mass Matrices for Dirac Neutrinos

We consider the possibility of neutrinos being Dirac particles and study minimal mass matrices with as much zero entries as possible. We find that up to 5 zero entries are allowed. Those matrices predict one vanishing mass state, CP conservation and U_{e3} either zero or proportional to R, where R is the ratio of the solar and atmospheric \Delta m^2. Matrices containing 4 zeros can be classified in categories predicting U_{e3} = 0, U_{e3} \neq 0 but no CP violation or |U_{e3}| \neq 0 and possible CP violation. Some cases allow to set constraints on the neutrino masses. The characteristic value of U_{e3} capable of distinguishing some of the cases with non-trivial phenomenological consequences is about R/2 \sin 2 \theta_{12}. Matrices containing 3 and less zero entries imply (with a few exceptions) no correlation for the observables. We outline models leading to the textures based on the Froggatt-Nielsen mechanism or the non-Abelian discrete symmetry D_4 \times Z_2.Comment: 32 pages, 3 figures. Comments and references added. To appear in JHE

Association Between Raised Blood Pressure and Dysglycemia in Hong Kong Chinese

OBJECTIVE—To investigate the association between raised blood pressure and dysglycemia

Safety and immunogenicity of therapeutic DNA vaccination in individuals treated with antiretroviral therapy during acute/early HIV-1 infection

Background: An effective therapeutic vaccine that could augment immune control of HIV-1 replication may abrogate or delay the need for antiretroviral therapy. AIDS Clinical Trials Group (ACTG) A5187 was a phase I/II, randomized, placebo-controlled, double-blinded trial to evaluate the safety and immunogenicity of an HIV-1 DNA vaccine (VRC-HVDNA 009-00-VP) in subjects treated with antiretroviral therapy during acute/early HIV-1 infection. (clinicaltrials.gov NCT00125099) Methods: Twenty healthy HIV-1 infected subjects who were treated with antiretroviral therapy during acute/early HIV-1 infection and had HIV-1 RNA<50 copies/mL were randomized to receive either vaccine or placebo. The objectives of this study were to evaluate the safety and immunogenicity of the vaccine. Following vaccination, subjects interrupted antiretroviral treatment, and set-point HIV-1 viral loads and CD4 T cell counts were determined 17–23 weeks after treatment discontinuation. Results: Twenty subjects received all scheduled vaccinations and discontinued antiretroviral therapy at week 30. No subject met a primary safety endpoint. No evidence of differences in immunogenicity were detected in subjects receiving vaccine versus placebo. There were also no significant differences in set-point HIV-1 viral loads or CD4 T cell counts following treatment discontinuation. Median set-point HIV-1 viral loads after treatment discontinuation in vaccine and placebo recipients were 3.5 and 3.7 log[sub]10 HIV-1 RNA copies/mL, respectively. Conclusions: The HIV-1 DNA vaccine (VRC-HIVDNA 009-00-VP) was safe but poorly immunogenic in subjects treated with antiretroviral therapy during acute/early HIV-1 infection. Viral set-points were similar between vaccine and placebo recipients following treatment interruption. However, median viral load set-points in both groups were lower than in historical controls, suggesting a possible role for antiretroviral therapy in persons with acute or early HIV-1 infection and supporting the safety of discontinuing treatment in this group. Trial Registration: Clinicaltrials.gov NCT0012509

Schwinger boson theory of anisotropic ferromagnetic ultrathin films

Ferromagnetic thin films with magnetic single-ion anisotropies are studied within the framework of Schwinger bosonization of a quantum Heisenberg model. Two alternative bosonizations are discussed. We show that qualitatively correct results are obtained even at the mean-field level of the theory, similar to Schwinger boson results for other magnetic systems. In particular, the Mermin-Wagner theorem is satisfied: a spontaneous magnetization at finite temperatures is not found if the ground state of the anisotropic system exhibits a continuous degeneracy. We calculate the magnetization and effective anisotropies as functions of exchange interaction, magnetic anisotropies, external magnetic field, and temperature for arbitrary values of the spin quantum number. Magnetic reorientation transitions and effective anisotropies are discussed. The results obtained by Schwinger boson mean-field theory are compared with the many-body Green's function technique.Comment: 14 pages, including 7 EPS figures, minor changes, final version as publishe

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Metformin promotes antitumor immunity via endoplasmic-reticulum-associated degradation of PD-L1

Metformin has been reported to possess antitumor activity and maintain high cytotoxic T lymphocyte (CTL) immune surveillance. However, the functions and detailed mechanisms of metformin’s role in cancer immunity are not fully understood. Here, we show that metformin increases CTL activity by reducing the stability and membrane localization of programmed death ligand-1 (PD-L1). Furthermore, we discover that AMP-activated protein kinase (AMPK) activated by metformin directly phosphorylates S195 of PD-L1. S195 phosphorylation induces abnormal PD-L1 glycosylation, resulting in its ER accumulation and ER-associated protein degradation (ERAD). Consistently, tumor tissues from metformin-treated breast cancer patients exhibit reduced PD-L1 levels with AMPK activation. Blocking the inhibitory signal of PD-L1 by metformin enhances CTL activity against cancer cells. Our findings identify a new regulatory mechanism of PD-L1 expression through the ERAD pathway and suggest that the metformin-CTLA4 blockade combination has the potential to increase the efficacy of immunotherapy