Inhibition of mTORC1 inhibits lytic replication of Epstein-Barr virus in a cell-type specific manner

BACKGROUND: Epstein-Barr virus is a human herpesvirus that infects a majority of the human population. Primary infection of Epstein-Barr virus (EBV) causes the syndrome infectious mononucleosis. This virus is also associated with several cancers, including Burkitt’s lymphoma, post-transplant lymphoproliferative disorder and nasopharyngeal carcinoma. As all herpesvirus family members, EBV initially replicates lytically to produce abundant virus particles, then enters a latent state to remain within the host indefinitely. METHODS: Through a genetic screen in Drosophila, we determined that reduction of Drosophila Tor activity altered EBV immediate-early protein function. To further investigate this finding, we inhibited mTOR in EBV-positive cells and investigated subsequent changes to lytic replication via Western blotting, flow cytometry, and quantitative PCR. The student T-test was used to evaluate significance. RESULTS: mTOR, the human homolog of Drosophila Tor, is an important protein at the center of a major signaling pathway that controls many aspects of cell biology. As the EBV immediate-early genes are responsible for EBV lytic replication, we examined the effect of inhibition of mTORC1 on EBV lytic replication in human EBV-positive cell lines. We determined that treatment of cells with rapamycin, which is an inhibitor of mTORC1 activity, led to a reduction in the ability of B cell lines to undergo lytic replication. In contrast, EBV-positive epithelial cell lines underwent higher levels of lytic replication when treated with rapamycin. CONCLUSIONS: Overall, the responses of EBV-positive cell lines vary when treated with mTOR inhibitors, and this may be important when considering such inhibitors as anti-cancer therapeutic agents

FCAST: Object Delivery for the Asynchronous Layered Coding (ALC) and NACK-Oriented Reliable Multicast (NORM) Protocols

Internet Engineering Task Force (IETF) Request for Comments 6968 (RFC 6968)This document introduces the FCAST reliable object (e.g., file) delivery application. It is designed to operate either on top of the underlying Asynchronous Layered Coding (ALC) / Layered Coding Transport (LCT) reliable multicast transport protocol or the NACK-Oriented Reliable Multicast (NORM) transport protocol

FCAST: Scalable Object Delivery for the ALC and NORM Protocols

IETF Internet DraftThis document introduces the FCAST object (e.g., file) delivery application on top of the ALC and NORM reliable multicast protocols. FCAST is a highly scalable application that provides a reliable object delivery service

DNA Unzipping Phase Diagram Calculated Via Replica Theory

We show how single-molecule unzipping experiments can provide strong evidence that the zero-force melting transition of long molecules of natural dsDNA should be classified as a phase transition of the higher-order type (continuous). Toward this end, we study a statistical-mechanics model for the fluctuating structure of a long molecule of dsDNA, and compute the equilibrium phase diagram for the experiment in which the molecule is unzipped under applied force. We consider a perfect-matching dsDNA model, in which the loops are volume-excluding chains with arbitrary loop exponent c. We include stacking interactions, hydrogen bonds, and main-chain entropy. We include sequence heterogeneity at the level of random sequences; in particular, there is no correlation in the base-pairing (bp) energy from one sequence position to the next. We present heuristic arguments to demonstrate that the low-temperature macrostate does not exhibit degenerate ergodicity breaking. We use this claim to understand the results of our replica-theoretic calculation of the equilibrium properties of the system. As a function of temperature, we obtain the minimal force at which the molecule separates completely. This critical-force curve is a line in the temperature-force phase diagram that marks the regions where the molecule exists primarily as a double helix versus the region where the molecule exists as two separate strands. We compare our random-sequence model to magnetic tweezer experiments performed on the 48 502 bp genome of bacteriophage λ. We find good agreement with the experimental data, which is restricted to temperatures between 24 and 50 °C. At higher temperatures, the critical-force curve of our random-sequence model is very different for that of the homogeneous-sequence version of our model. For both sequence models, the critical force falls to zero at the melting temperature T$_c$ like $|T−T_c|$$^α$. For the homogeneous-sequence model, $\alpha$=1/2 almost exactly, while for the random-sequence model, $\alpha$$\approx$0.9. Importantly, the shape of the critical-force curve is connected, via our theory, to the manner in which the helix fraction falls to zero at T$_c$. The helix fraction is the property that is used to classify the melting transition as a type of phase transition. In our calculation, the shape of the critical-force curve holds strong evidence that the zero-force melting transition of long natural dsDNA should be classified as a higher-order (continuous) phase transition. Specifically, the order is 3rd or greater.Physic

Potential markets for advanced satellite communications

This report identifies trends in the volume and type of traffic offered to the U.S. domestic communications infrastructure and extrapolates these trends through the year 2011. To describe how telecommunications service providers are adapting to the identified trends, this report assesses the status, plans, and capacity of the domestic communications infrastructure. Cable, satellite, and radio components of the infrastructure are examined separately. The report also assesses the following major applications making use of the infrastructure: (1) Broadband services, including Broadband Integrated Services Digital Network (BISDN), Switched Multimegabit Data Service (SMDS), and frame relay; (2) mobile services, including voice, location, and paging; (3) Very Small Aperture Terminals (VSAT), including mesh VSAT; and (4) Direct Broadcast Satellite (DBS) for audio and video. The report associates satellite implementation of specific applications with market segments appropriate to their features and capabilities. The volume and dollar value of these market segments are estimated. For the satellite applications able to address the needs of significant market segments, the report also examines the potential of each satellite-based application to capture business from alternative technologies

Validity of Body Volume Estimates from Infrared 3-dimensional Scanning and Dual-energy X-ray Absorptiometry as Compared to Air Displacement Plethysmography

Traditional methods of estimating body volume (BV) such as hydrostatic weighing and air-displacement plethysmography (ADP) could theoretically be replaced using BV estimates obtained by dual-energy x-ray absorptiometry (DXA) or infrared 3-dimensional (3D) scanning devices. Multiple 3D scanning technologies have recently become popularized, including scanners that acquire data through pattern deformations caused by the projected light over the 3D object (i.e., structured light [SL] scanners) or by calculating depth from the time it takes reflected photons to reach the scanner’s image sensor (i.e. time of flight [ToF] scanners). While these 3D scanning technologies currently predict body composition based primarily on circumference estimates, the BV estimates obtained by this technology could be used to predict body composition if the BV estimates are validated. PURPOSE: The purpose of this analysis was to examine the validity of BV estimates obtained from DXA-derived formulas and multiple types of 3D scanners as compared to ADP. METHODS: At a single research visit, BV estimates were obtained via ADP, prediction from DXA output, and three infrared 3D scanners in a sample of 102 adults (64 F, 38 M; age: 29.2 ± 13.4 y; BMI: 24.3 ± 3.9 kg/m2; BF%: 24.6 ± 8.3%). The 3D scanners included a SL scanner with a static configuration (SL-S) in which the scanner and participant are stationary during assessments, a SL scanner with a dynamic configuration (SL-D) in which the participant is rotated during the scan, and a ToF scanner with a dynamic configuration. ADP was designated as the criterion method, and BV estimates were compared using one-way ANOVA and post hoc testing with Bonferroni correction. Additional evaluations were conducted using the coefficient of determination (R2), constant error (CE), total error (TE), and 95% limits of agreement (LOA). RESULTS: DXA-derived BV estimates were valid and produced the lowest error of all methods (p \u3e 0.05; R2: 1.00; CE: 0 – 1.4 L; TE: 0.8 – 1.5 L; LOA: 1.0 – 1.8 L). BVSL-D did not differ from BVADP (p \u3e 0.05; R2: 1.00; CE: -3.9 L; TE: 4.0 L; LOA: 2.5 L), although errors were higher than the DXA-derived equations. The SL-S and ToF scanners did not produce valid estimates, although they differed in the direction and magnitude of errors. The SL-S scanner overestimated BV relative to BVADP (p=0.01; R2: 0.94; CE: 7.0 L; TE: 8.0 L; LOA: 7.3 L), while the ToF scanner underestimated BV relative to BVADP (p \u3c 0.001; R2: 0.99; CE: -9.7 L; TE: 9.9 L; LOA: 4.6 L). CONCLUSION: The present results add to the growing research indicating that DXA-derived BV may be an acceptable replacement to traditional methods of BV assessment. Although the SL-D 3D scanner exhibited better validity of BV estimates as compared to the other scanners, improvements in the validity of BV estimates obtained from 3D scanners are necessary before this technology can be viewed as a viable alternative to traditional methods of BV assessment

A Bioinformatics Method Identifies Prominent Off-targeted Transcripts in RNAi Screens

Because off-target effects hamper interpretation and validation of RNAi screens, we developed a bioinformatics method, Genome-wide Enrichment of Seed Sequence matches (GESS), to identify candidate off-targeted transcripts from direct analysis of primary screening data. GESS identified a prominent off-targeted transcript in several screens, including MAD2 in a screen for components of the spindle assembly checkpoint. We demonstrate how incorporation of the results of GESS analysis can enhance the validation rate in RNAi screens

The effect of depression management on diabetes and hypertension outcomes in low- and middle-income countries: a systematic review protocol

Abstract Background Depression and non-communicable diseases (NCDs) account for a growing burden on health systems in low- and middle-income countries (LMICs). Depression is generally associated with the outcomes of NCDs and is an important barrier to consistent NCD care management. There is great need to understand the efficacy of interventions to treat depression for people with NCDs, but there is a paucity of evidence of the efficacy of the interventions in LMICs. Therefore, the broad objective of this review is to systematically review the literature on the effectiveness of depression management among patients with diabetes and hypertension to improve outcomes. Methods This is a systematic review to assess the evidence of the effect of depression management in diabetic and hypertensive patients on diabetes and hypertension outcomes in LMICs. Two independent reviewers will search articles on PubMed, EMBASE, PsycINFO, and Global Index Medicus. Two reviewers will then screen the articles independently based on predefined criteria. We will use standard methods as recommended by the Cochrane Collaboration of assessing quality of evidence and publish our report using the PRISMA guidelines. Discussion The findings from this review will provide evidence to be used in guiding practice and policy on how to integrate depression management in diabetes and hypertension clinics. Systematic review registration PROSPERO CRD4201706825