HIV Specific B Cell Response in Patients With Broadly Neutralizing Serum Activity

Antibodies to conserved epitopes on the HIV surface protein gp140 can protect against infection in non-human primates, suggesting that vaccines that elicit such antibodies would be protective. Some HIV infected individuals develop high titers of broadly neutralizing IgG antibodies in their serum, but until recently very little was known about the specificity and activity of these antibodies. To characterize the broadly neutralizing memory antibody responses to HIV we cloned 1078 antibodies from HIV envelope binding memory B cells from eight HIV infected patients with broadly neutralizing antibodies. We found that in these patients, the B cell memory response to gp140 is composed of up to 50 independent clones expressing high affinity antibodies to the gp120 variable loops, the CD4 binding site, the co-receptor binding site, to a new neutralizing epitope that is in the same region of gp120 as the CD4 binding site and to gp41. In four patients highly potent broadly neutralizing antibody clones directed to the CD4 binding site were isolated. Despite extensive hypermutation, these broadly neutralizing CD4bs antibodies shared a consensus sequence of 68 IgH chain amino acids and arose independently from two related IgH genes. Thus, the IgG memory B cell compartment in the selected group of patients with broad serum activity to HIV is comprised of multiple clonal responses. Neutralizing activity is directed against several epitopes on gp120 with some closely related CD4 binding site directed antibody clones showing highly potent neutralizing activity. For the first time, this study has attempted to systematically describe on a monoclonal level the composition of broadly neutralizing serum activity against HIV. The techniques and antibodies presented in this work are transforming our understanding of possible targets and routes for HIV vaccine strategies and provide powerful tools for possible HIV treatment approaches

Autonomous frequency domain identification: Theory and experiment

The analysis, design, and on-orbit tuning of robust controllers require more information about the plant than simply a nominal estimate of the plant transfer function. Information is also required concerning the uncertainty in the nominal estimate, or more generally, the identification of a model set within which the true plant is known to lie. The identification methodology that was developed and experimentally demonstrated makes use of a simple but useful characterization of the model uncertainty based on the output error. This is a characterization of the additive uncertainty in the plant model, which has found considerable use in many robust control analysis and synthesis techniques. The identification process is initiated by a stochastic input u which is applied to the plant p giving rise to the output. Spectral estimation (h = P sub uy/P sub uu) is used as an estimate of p and the model order is estimated using the produce moment matrix (PMM) method. A parametric model unit direction vector p is then determined by curve fitting the spectral estimate to a rational transfer function. The additive uncertainty delta sub m = p - unit direction vector p is then estimated by the cross spectral estimate delta = P sub ue/P sub uu where e = y - unit direction vectory y is the output error, and unit direction vector y = unit direction vector pu is the computed output of the parametric model subjected to the actual input u. The experimental results demonstrate the curve fitting algorithm produces the reduced-order plant model which minimizes the additive uncertainty. The nominal transfer function estimate unit direction vector p and the estimate delta of the additive uncertainty delta sub m are subsequently available to be used for optimization of robust controller performance and stability

Quasifission and fusion-fission in massive nuclei reactions. Comparison of reactions leading to the Z=120 element

The yields of evaporation residues, fusion-fission and quasifission fragments in the $^{48}$Ca+$^{144,154}$Sm and $^{16}$O+$^{186}$W reactions are analyzed in the framework of the combined theoretical method based on the dinuclear system concept and advanced statistical model. The measured yields of evaporation residues for the $^{48}$Ca+$^{154}$Sm reaction can be well reproduced. The measured yields of fission fragments are decomposed into contributions coming from fusion-fission, quasifission, and fast-fission. The decrease in the measured yield of quasifission fragments in $^{48}$Ca+$^{154}$Sm at the large collision energies and the lack of quasifission fragments in the $^{48}$Ca+$^{144}$Sm reaction are explained by the overlap in mass-angle distributions of the quasifission and fusion-fission fragments. The investigation of the optimal conditions for the synthesis of the new element $Z$=120 ($A$=302) show that the $^{54}$Cr+$^{248}$Cm reaction is preferable in comparison with the $^{58}$Fe+$^{244}$Pu and $^{64}$Ni+$^{238}$U reactions because the excitation function of the evaporation residues of the former reaction is some orders of magnitude larger than that for the last two reactions.Comment: 27 pages, 12 figures, submitted to Phys. Rev.

Chinese medicine in the West 2009

In January 1985 The Journal of Chinese Medicine published an edited transcript of a discussion called ‘Acupuncture in the West’ between Peter Deadman, Ted Kaptchuk, Giovanni Maciocia and Felicity Moir. It was a particularly popular article and to celebrate the 30th anniversary of the JCM we decided to convene another discussion, in London in March 2009. Present this time were Peter Deadman (PD), Hugh MacPherson (HM), Daniel Maxwell (DM), Felicity Moir (FM) and Volker Scheid (VS). All are past or present practitioners of acupuncture and/or herbal medicine

A combined FEG-SEM and TEM study of silicon nanodot assembly

Nanodots forming dense assembly on a substrate are difficult to characterize in terms of size, density, morphology and cristallinity. The present study shows how valuable information can be obtained by a combination of electron microscopy techniques. A silicon nanodots deposit has been studied by Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy (TEM) to estimate essentially the dot size and density, quantities emphasized because of their high interest for application. High resolution SEM indicates a density of 1.6 × 1012 dots/cm2 for a 5 nm to 10 nm dot size. TEM imaging using a phase retrieval treatment of a focus series gives a higher dot density (2 × 1012 dots/cm2) for a 5 nm dot size. High Resolution Transmission Electron Microscopy (HRTEM) indicates that the dots are crystalline which is confirmed by electron diffraction. According to HRTEM and electron diffraction, the dot size is about 3 nm which is significantly smaller than the SEM and TEM results. These differences are not contradictory but attributed to the fact that each technique is probing a different phenomenon. A core-shell structure for the dot is proposed which reconcile all the results. All along the study, Fourier transforms have been widely used under many aspects

HIV-1 antibody 3BNC117 suppresses viral rebound in humans during treatment interruption

Interruption of combination antiretroviral therapy (ART) in HIV-1-infected individuals leads to rapid viral rebound. Here we report the results of a phase IIa open label clinical trial evaluating 3BNC117, a broad and potent neutralizing antibody (bNAb) against the CD4 binding site of HIV-1 Env1, in the setting of analytical treatment interruption (ATI) in 13 HIV-1-infected individuals. Participants with 3BNC117-sensitive virus outgrowth cultures were enrolled. Two or four 30 mg/kg infusions of 3BNC117, separated by 3 or 2 weeks, respectively, were generally well tolerated. The infusions were associated with a delay in viral rebound for 5-9 weeks after 2 infusions, and up to 19 weeks after 4 infusions, or an average of 6.7 and 9.9 weeks respectively, compared with 2.6 weeks for historical controls (p=<1e-5). Rebound viruses arose predominantly from a single provirus. In most individuals, emerging viruses showed increased resistance indicating escape. However, 30% of participants remained suppressed until antibody concentrations waned below 20 μg/ml, and the viruses emerging in all but one of these individuals showed no apparent resistance to 3BCN117, suggesting failure to escape over a period of 9-19 weeks. We conclude that administration of 3BNC117 exerts strong selective pressure on HIV-1 emerging from latent reservoirs during ATI in humans

Traffic Centralization and Digital Sovereignty: An Analysis Under the Lens of DNS Servers

The Domain Name System (DNS) service is one of the pillars of the Internet. This service allows users to access websites on the Internet through easy-to-remember domain names rather than complex numeric IP addresses. DNS acts as a directory that translates the domain names into a corresponding IP address, allowing communication between computers on different networks. However, the concentration of DNS service providers on the Internet affects user security, privacy, and network accessibility. The reliance on a small number of large DNS providers can lead to (a) risks of data breaches and disruption of service in the event of failures and (b) concerns about the digital sovereignty of countries regarding DNS hosting. In this sense, this work approaches this issue of DNS concentration on the Internet by presenting a solution to measure DNS hosting centralization and digital sovereignty in countries. With the data obtained through these measurements, relevant questions are answered, such as which are the top-10 DNS providers, if there is DNS centralization, and how dependent countries are on such providers.Comment: 8 pages, 7 figure

Influence of the 6^1S_0-6^3P_1 Resonance on Continuous Lyman-alpha Generation in Mercury

Continuous coherent radiation in the vacuum-ultraviolet at 122 nm (Lyman-alpha) can be generated using sum-frequency mixing of three fundamental laser beams in mercury vapour. One of the fundamental beams is at 254 nm wavelength, which is close to the 6^1S_0-6^3P_1 resonance in mercury. Experiments have been performed to investigate the effect of this one-photon resonance on phasematching, absorption and the nonlinear yield. The efficiency of continuous Lyman-alpha generation has been improved by a factor of 4.5.Comment: 8 pages, 7 figure