Evidence for HIV-1 cure after CCR5Δ32/Δ32 allogeneic haemopoietic stem-cell transplantation 30 months post analytical treatment interruption: a case report

Background The ‘London Patient’ (IciS-36) underwent allogeneic stem cell transplantation with cells lacking the expression of CCR5 (CCR5Δ32/Δ32) and remission was reported at 18 months. Here we present longer term data including sampling from diverse HIV-1 reservoir sites. Methods Ultra-sensitive plasma, semen and cerebrospinal fluid (CSF) viral load assays were used to detect HIV-1 RNA. In gut biopsies and lymph node tissue cell-copy number, total HIV-1 DNA levels were quantified in multiple replicates using droplet digital PCR (ddPCR) and real time qPCR. Furthermore, presence of intact proviral DNA was analyzed using multiplex ddPCR targeting the packaging signal (psi) and env. Intracellular cytokine staining was used to measure HIV-1 specific T cell responses. Detuned and low avidity antibody assays were used to measure the humoral response to HIV-1. We predicted the probability of rebound using a previously-developed mathematical model and inference approach. Findings HIV-1 viral load in plasma has remained undetectable using an assay with detection limit of 1 copy/ml up to 29 months. The most recent CD4 count was 430 cells per µL (20.3%). There was a very low level positive signal for HIV-1 DNA in peripheral CD4 memory cells. Semen viral load was undetectable in both plasma (LLD 99% probability of cure with 90% donor chimerism. Interpretation The ‘London Patient’ has been in HIV remission for 29 months with no detectable replication-competent virus in blood, CSF, intestinal tissue, or lymphoid tissue. Donor chimerism has been maintained at 99% in peripheral T cells. We conclude that this represents HIV-1 cure

DFQIoV: Design of a Dynamic Fan-Shaped-Clustering Model for QoS-aware Routing in IoV Networks

Internet of Vehicles (IoV) is a steadily growing field of research that deals with highly ad-hoc wireless networks. These networks require design of high-speed & high-efficiency routing models, that can be applied to dynamically changing network scenarios. Existing models that perform this task are highly complex and require larger delays for estimation of dynamic routes. While, models that have faster performance, do not consider comprehensive parameters, which limits their applicability when used for large-scale network scenarios. To overcome these limitations, this text proposes design of a novel dynamic fan-shaped clustering model for QoS-aware routing in IoV networks. The model initially collects network information sets including node positions, & energy levels, and combines them with their temporal packet delivery & throughput performance levels. These aggregated information sets are processed via a hybrid bioinspired fan shaped clustering model, that aims at optimization of routing performance via deployment of dynamic clustering process. The model performs destination-aware routing process which assists in reducing communication redundances. This is done via a combination of Elephant Herding Optimization (EHO) with Particle Swarm Optimization (PSO), which integrates continuous learning for router level operations. The integrated model is able to reduce communication delays by 5.9%, while improving energy efficiency by 8.3%, throughput by 4.5%, and packet delivery performance by 1.4% under different network scenarios. Due to which the proposed model is capable of deployment for a wide variety of dynamic network scenarios

ENHANCED REVERSIBLE IMAGE DATA HIDING BASED ON BLOCK HISTOGRAM SHIFTING AND PADHM

Due to the enhanced digital media on the web, information security and privacy protection issue have attracted the eye of information communication. Information hiding has become a subject of sizable im-portance. Currently each day there's very big drawback of information hacking into the networking space. There is variety of techniques offered within the trade to over-come this drawback. So, information hiding within the encrypted image is one in all the solutions, however the matter is that the original cover can't be losslessly recov-ered by this system. That’s why recently; additional and additional attention is paid to reversible information concealing in encrypted pictures however this technique drawback low hardiness. A completely unique technique is planned by reserving for embedding information be-fore encoding of the image takes place with the offered algorithmic rule. Currently the authentic person will hide the information simply on the image to produce authen-tication. The transmission and exchange of image addi-tionally desires a high security .This is the review paper regarding this reversible information hiding algorithms obtainable. As a result, because of histogram enlarge-ment and bar graph shifting embedded message and also the host image may be recovered dead. The embedding rate is enhanced and PSNR magnitude relation using novel technique

A Tail of Tetherin: How Pandemic HIV-1 Conquered the World

The study of successful versus failed zoonotic infections may provide important clues of how viral infection is naturally prevented. In this issue of Cell Host & Microbe, a collaborative group led by Frank Kirchhoff uncovers an important piece of the pandemic HIV-1 puzzle

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An Approach for Solving Multiple Travelling Salesman Problem using Ant Colony Optimization

Ant Colony Optimization (ACO) is a heuristic algorithm which has been proven a successful technique and applied to a number of combinatorial optimization (CO) problems. The traveling salesman problem (TSP) is one of the most important combinatorial problems. Multiple traveling salesman problem (MTSP) is a typical computationally complex combinatorialOptimization problem, which is an extension of the famous traveling salesman problem (TSP). The paper proposed an approach to show how the ant colony optimization (ACO) can be applied to the MTSP with ability constraint. There are several reasons for the choice of the TSP as the problem to explain the working of ACO algorithms: it is an important NP-hard optimization problem that arises in several applications; it is a problem to which ACO algorithms are easily applied; it is easily understandable, so that the algorithm behavior is not obscured by too many technicalities; and it is a standard test bed for new algorithmic ideas as a good performance on the TSP is often taken as a proof of their usefulness. Keywords— Ant colony optimization, Traveling salesman proble

Tailoring of the electronic property of Zn-BTC metal–organic framework via ligand functionalization: an ab initio investigation

Metal–organic frameworks (MOFs) are porous materials of recent interest due to their promising properties for technological applications. In this paper, the structure–property relationships of pristine and functionalized Zn-BTC (Zn3(BTC)2) MOFs are investigated. The results based on density functional theory (DFT) find that MOFs with coordinatively saturated secondary building units (SBU) are metallic, and MOFs with coordinatively unsaturated SBU are semi-conducting. The ligand functionalization with electron acceptor (cyano-) and electron donor (amino-) groups appears to tailor the electronic properties of Zn-BTC MOFs; amino-functionalization led to a significant upward shift of the band-edges whereas cyano-functionalization yields shifting of band-edges in the opposite direction, which led to a narrowing of the band gap. Modifying the electronic properties through such ligand functionalization design principles can be useful in engineering MOFs for gas sensing and device applications

TLR4-Mediated Pathway Triggers Interferon-Independent G0 Arrest and Antiviral SAMHD1 Activity in Macrophages

Macrophages exist predominantly in two distinct states, G0 and a G1-like state that is accompanied by phosphorylation of SAMHD1 at T592. Here we demonstrate that TLR4 activation mediated by LPS or ingestion of whole E. Coli can potently induce G0 arrest and SAMHD1 antiretroviral activity by a novel IFN-independent pathway. This pathway is not sensitive to TBK1 depletion or to block of IRF3 translocation, but is sensitive to TRIF depletion by siRNA, indicating that the pathway requires TLR4 engagement with TRIF but not involvement of TBK1 dependent IRF3 translocation. Exclusive Myd88 activators, such as Tenascin C, a product of tissue breakdown that activates TLR4, and Flagellin, a bacterial protein recognized by TLR5, are unable to trigger G0 arrest or SAMHD1 dephosphorylation, demonstrating this arrest is also Myd88- and thus NFkB-independent. The G0 arrest is accompanied by p21 upregulation and CDK1 depletion, consistent with the observed SAMHD1 dephosphorylation at T592. Furthermore, we show by siRNA knockdown of SAMHD1 that this TLR4 activated pathway is able to potently block HIV-1 infection in macrophages specifically via SAMHD1. Together, these data demonstrate that macrophages can mobilize an intrinsic cell arrest and anti-viral state by activating TLR4 prior to IFN secretion, thereby highlighting the importance of cell cycle regulation as a response to pathogen associated danger signals in macrophages

Low use of statins and other coronary secondary prevention therapies in primary and secondary care in India.

ObjectiveTo determine the frequency of use of pharmacotherapy with aspirin, beta blocker, statin, and angiotensin-converting enzyme (ACE) inhibitor in patients with stable coronary heart disease (CHD) among physicians at different levels of health care in Rajasthan state, India.MethodsPhysicians practicing at tertiary hospitals and clinics at tertiary, secondary and primary levels were contacted. Prescriptions of CHD patients were audited and descriptive statistics reported.ResultsWe evaluated 2,993 prescriptions (tertiary hospital discharge 711, tertiary 688, secondary 1,306, and primary 288). Use of aspirin was in 2,713 (91%) of prescriptions, beta blockers 2,057 (69%), ACE inhibitors or angiotensin receptor blockers (ARBs) 2,471 (82%), and statins 2,059 (69%). Any one of these drugs was prescribed in 2,991 (100%), any two in 2,880 (96%), any three in 1,740 (58%), and all four in 1,062 (35.5%) (P < 0.001). As compared to tertiary hospital, prescriptions at tertiary, secondary, and primary levels were lower: aspirin (96% vs 95%, 91%, 67%), beta blockers (80% vs 62%, 66%, 70%), statins (87% vs 82%, 62%, 21%): two drugs (98% vs 96%, 98%, 85%), three drugs (75% vs 58%, 55%, 28%), or four drugs (54% vs 44%, 28%, 7%) (P < 0.01). Use of ACE inhibitors/ARBs was similar while nitrates (43% vs 23%, 43%, 70%), dihydropyridine calcium channel blockers (12% vs 15%, 30%, 47%), and multivitamins (6% vs 26%, 37%, 47%) use was more in secondary and primary care.ConclusionsThere is suboptimal use of various evidence-based drugs (aspirin, beta blockers, ACE inhibitors, and statins) for secondary prevention of CHD in India