An analytical model of eddy current ferrite-core probes

An analytical model of an axisymmetric eddy current probe with a cylindrical ferrite core above a layered conductive half-space is developed. Initially we consider the magnetic vector potential of a circular filament coaxial with a ferrite core over a layered conducting half-space. The principle of superposition is then used to derive close-form expressions for both the electromagnetic field and the impedance of a coil from the filament field. Rather than locating the probe in infinite space, it is confined coaxially within a circularly cylindrical boundary on which the vector potential field is zero. The radius of this artificial boundary is large in order to ensure that does not interfere substantially with the field near the probe. By using a truncated region in this way, the vector potential in the probe region can be expanded as a series rather than an integral form. Thus the solution of the problem amounts to finding the expansion coeefficients in the series. The numerical predictions of probe impedance have been compared with experimental data showing good agreement

Relationship between intact HIV-1 proviruses in circulating CD4+ T cells and rebound viruses emerging during treatment interruption.

Combination antiretroviral therapy controls but does not cure HIV-1 infection because a small fraction of cells harbor latent viruses that can produce rebound viremia when therapy is interrupted. The circulating latent virus reservoir has been documented by a variety of methods, most prominently by viral outgrowth assays (VOAs) in which CD4+ T cells are activated to produce virus in vitro, or more recently by amplifying proviral near full-length (NFL) sequences from DNA. Analysis of samples obtained in clinical studies in which individuals underwent analytical treatment interruption (ATI), showed little if any overlap between circulating latent viruses obtained from outgrowth cultures and rebound viruses from plasma. To determine whether intact proviruses amplified from DNA are more closely related to rebound viruses than those obtained from VOAs, we assayed 12 individuals who underwent ATI after infusion of a combination of two monoclonal anti-HIV-1 antibodies. A total of 435 intact proviruses obtained by NFL sequencing were compared with 650 latent viruses from VOAs and 246 plasma rebound viruses. Although, intact NFL and outgrowth culture sequences showed similar levels of stability and diversity with 39% overlap, the size of the reservoir estimated from NFL sequencing was larger than and did not correlate with VOAs. Finally, intact proviruses documented by NFL sequencing showed no sequence overlap with rebound viruses; however, they appear to contribute to recombinant viruses found in plasma during rebound

The effect of the antisickling compound GBT1118 on the permeability of red blood cells from patients with sickle cell anemia.

Sickle cell anemia (SCA) is one of the commonest severe inherited disorders. Nevertheless, effective treatments remain inadequate and novel ones are avidly sought. A promising advance has been the design of novel compounds which react with hemoglobin S (HbS) to increase oxygen (O2 ) affinity and reduce sickling. One of these, voxelotor (GBT440), is currently in advanced clinical trials. A structural analogue, GBT1118, was investigated in the current work. As RBC dehydration is important in pathogenesis of SCA, the effect of GBT1118 on RBC cation permeability was also studied. Activities of Psickle , the Gardos channel and the KCl cotransporter (KCC) were all reduced. Gardos channel and KCC activities were also inhibited in RBCs treated with Ca2+ ionophore or the thiol reagent N-ethylmaleimide, indicative of direct effects on these two transport systems. Consistent with its action on RBC membrane transporters, GBT1118 significantly increased RBC hydration. RBC hemolysis was reduced in a nonelectrolyte lysis assay. Further to its direct effects on O2 affinity, GBT1118 was therefore found to reduce RBC shrinkage and fragility. Findings reveal important effects of GBT1118 on protecting sickle cells and suggest that this is approach may represent a useful therapy for amelioration of the clinical complications of SCA.Sultanate of Oman His Majesty Sultan Qaboos's 1000 grants British Heart Foundatio

Optical properties of quantum wires: Disorder-scattering in the Lloyd-model

The Lloyd model is extended to the exciton problem in quasi one-dimensional structures to study the interplay between the Coulomb attraction and disorder scattering. Within this model the averaging and resummation of the locator series can be performed analytically. As an application, the optical absorption in quantum box wires is investigated. Without electron-hole interaction, fluctuations in the well-width lead to an asymmetric broadening of the minibands with respect to the lower and upper band-edges.Comment: 7 pages, 6 figure

A Dynamic Programming Approach to Adaptive Fractionation

We conduct a theoretical study of various solution methods for the adaptive fractionation problem. The two messages of this paper are: (i) dynamic programming (DP) is a useful framework for adaptive radiation therapy, particularly adaptive fractionation, because it allows us to assess how close to optimal different methods are, and (ii) heuristic methods proposed in this paper are near-optimal, and therefore, can be used to evaluate the best possible benefit of using an adaptive fraction size. The essence of adaptive fractionation is to increase the fraction size when the tumor and organ-at-risk (OAR) are far apart (a "favorable" anatomy) and to decrease the fraction size when they are close together. Given that a fixed prescribed dose must be delivered to the tumor over the course of the treatment, such an approach results in a lower cumulative dose to the OAR when compared to that resulting from standard fractionation. We first establish a benchmark by using the DP algorithm to solve the problem exactly. In this case, we characterize the structure of an optimal policy, which provides guidance for our choice of heuristics. We develop two intuitive, numerically near-optimal heuristic policies, which could be used for more complex, high-dimensional problems. Furthermore, one of the heuristics requires only a statistic of the motion probability distribution, making it a reasonable method for use in a realistic setting. Numerically, we find that the amount of decrease in dose to the OAR can vary significantly (5 - 85%) depending on the amount of motion in the anatomy, the number of fractions, and the range of fraction sizes allowed. In general, the decrease in dose to the OAR is more pronounced when: (i) we have a high probability of large tumor-OAR distances, (ii) we use many fractions (as in a hyper-fractionated setting), and (iii) we allow large daily fraction size deviations.Comment: 17 pages, 4 figures, 1 tabl

Statin Inhibition of Fc Receptor–Mediated Phagocytosis by Macrophages Is Modulated by Cell Activation and Cholesterol

Objectives— An inflammatory response to altered lipoproteins that accumulate in the arterial wall is a major component of the pathogenesis of atherosclerosis. Statins reduce plasma levels of low-density lipoprotein (LDL) and are effective treatments for atherosclerosis. It is hypothesized that they also modulate inflammation. The aim of this study was to examine whether lovastatin inhibits macrophage inflammatory processes and clarify its mechanism of action. Methods and Results— We examined the effects of statins on phagocytosis of antibody-coated red blood cells by cultured human monocytes and mouse peritoneal macrophages. Lovastatin, simvastatin, and zaragozic acid, a squalene synthase inhibitor, blocked Fc receptor–mediated phagocytosis by cultured human monocytes and mouse peritoneal macrophages. The inhibitory effect of lovastatin on Fc receptor–mediated phagocytosis was prevented completely by addition of mevalonate, farnesyl pyrophosphate, LDL, or cholesterol to the culture medium. The inhibitory effect of zaragozic acid was reversed by addition of LDL, but not by the addition of geranylgeranyl pyrophosphate, to the medium. In addition, the effect of lovastatin on phagocytosis is a function of cell activation because treatment of cells with tumor necrosis factor-α or lipopolysaccharide prevented inhibition of phagocytosis by lovastatin. Conclusions— The inhibition of Fc receptor–mediated phagocytosis of lovastatin is related to its effect on cholesterol biosynthesis rather than its effect on the formation of isoprenoids

Surface structure and solidification morphology of aluminum nanoclusters

Classical molecular dynamics simulation with embedded atom method potential had been performed to investigate the surface structure and solidification morphology of aluminum nanoclusters Aln (n = 256, 604, 1220 and 2048). It is found that Al cluster surfaces are comprised of (111) and (001) crystal planes. (110) crystal plane is not found on Al cluster surfaces in our simulation. On the surfaces of smaller Al clusters (n = 256 and 604), (111) crystal planes are dominant. On larger Al clusters (n = 1220 and 2048), (111) planes are still dominant but (001) planes can not be neglected. Atomic density on cluster (111)/(001) surface is smaller/larger than the corresponding value on bulk surface. Computational analysis on total surface area and surface energies indicates that the total surface energy of an ideal Al nanocluster has the minimum value when (001) planes occupy 25% of the total surface area. We predict that a melted Al cluster will be a truncated octahedron after equilibrium solidification.Comment: 22 pages, 6 figures, 34 reference

Characterization of Intact Proviruses in Blood and Lymph Node from HIV-Infected Individuals Undergoing Analytical Treatment Interruption.

The role of lymphoid tissue as a potential source of HIV-1 rebound following interruption of antiretroviral therapy (ART) is uncertain. To address this issue, we compared the latent viruses obtained from CD4+ T cells in peripheral blood and lymph nodes to viruses emerging during treatment interruption. Latent viruses were characterized by sequencing near-full-length (NFL) proviral DNA and env from viral outgrowth assays (VOAs). Five HIV-1-infected individuals on ART were studied, four of whom participated in a clinical trial of a TLR9 agonist that included an analytical treatment interruption. We found that 98% of intact or replication-competent clonal sequences overlapped between blood and lymph node. In contrast, there was no overlap between 205 latent reservoir and 125 rebound sequences in the four individuals who underwent treatment interruption. However, rebound viruses could be accounted for by recombination. The data suggest that CD4+ T cells carrying latent viruses circulate between blood and lymphoid tissues in individuals on ART and support the idea that recombination may play a role in the emergence of rebound viremia.IMPORTANCE HIV-1 persists as a latent infection in CD4+ T cells that can be found in lymphoid tissues in infected individuals during ART. However, the importance of this tissue reservoir and its contribution to viral rebound upon ART interruption are not clear. In this study, we sought to compare latent HIV-1 from blood and lymph node CD4+ T cells from five HIV-1-infected individuals. Further, we analyzed the contribution of lymph node viruses to viral rebound. We observed that the frequencies of intact proviruses were the same in blood and lymph node. Moreover, expanded clones of T cells bearing identical proviruses were found in blood and lymph node. These latent reservoir sequences did not appear to be the direct origin of rebound virus. Instead, latent proviruses were found to contribute to the rebound compartment by recombination