HIV-2 Neutralization Sensitivity in Relation to Co-Receptor Entry Pathways and Env Motifs

HIV-2, compared to HIV-1, elicits potent and broadly neutralizing antibodies, and uses a broad range of co-receptors. However, both sensitivity to neutralization and breadth of co-receptor use varies between HIV-2 isolates, and the molecular background is still not fully understood. Thus, in the current study, we have deciphered relationships between HIV-2 neutralization sensitivity, co-receptor use and viral envelope glycoprotein (Env) molecular motifs. A panel of primary HIV-2 isolates, with predefined use of co-receptors, was assessed for neutralization sensitivity using a set of HIV-2 Env-directed monoclonal antibodies and co-receptor indicator cell lines. Neutralization sensitivity of the isolates was analysed in relation target cell co-receptor expression, in addition to amino acid motifs and predicted structures of Env regions. Results showed that HIV-2 isolates were more resistant to neutralizing antibodies when entering target cells via the alternative co-receptor GPR15, as compared to CCR5. A similar pattern was noted for isolates using the alternative co-receptor CXCR6. Sensitivity to neutralizing antibodies appeared also to be linked to specific Env motifs in V1/V2 and C3 regions. Our findings suggest that HIV-2 sensitivity to neutralization depends both on which co-receptor is used for cell entry and on specific Env motifs. This study highlights the multifactorial mechanisms behind HIV-2 neutralization sensitivity.     

Induced Zinc Loss Produces Heterogenous Biological Responses in Melanoma Cells

Zinc levels in serum and/or tissue are reported to be altered in melanoma with unknown effects on melanoma development and biology. The purpose of this study was to examine the effects of acute chelation of free intracellular zinc pools in melanoma cell lines Bowes and A375, as well as selected melanoma tissue explants with high or low intracellular free zinc. Zinc chelating agent TPEN at the concentration of 25 µM was employed during 48 h, which significantly reduced intracellular free zinc while decreasing melanoma cell proliferation, inducing G1/S arrest and cell damage leading to mitochondrial, caspase-dependent apoptosis. Chelation of free zinc was also associated with increased generation of superoxide in cell lines but not marked lysosomal membrane damage. Conversely, melanoma explant cultures mostly displayed time-dependent loss of lysosomal membrane integrity in the presence of slowly growing superoxide levels. Loss of free zinc-dependent p53 activity was similarly disparate in individual melanoma models. Surviving melanoma cells were arrested in the cell cycle, and varying proportions of them exhibited features characteristic of premature senescence, which increased in time despite zinc reloading. The present results show that melanoma cells with varying free zinc levels respond to its acute loss in a number of individual ways, reflecting activated mechanisms including oxidative stress, lysosomal damage, and p53 activity leading to heterogenous outcomes including cell death, transient, and/or permanent cell cycle arrest and premature senescence.     

Facile Microwave Assisted Synthesis of Silver Nanostars for Ultrasensitive Detection of Biological Analytes by SERS

We report a very simple, rapid and reproducible method for the fabrication of anisotropic silver nanostars (AgNS) that can be successfully used as highly efficient SERS substrates for different bioanalytes, even in the case of a near-infra-red (NIR) excitation laser. The nanostars have been synthesized using the chemical reduction of Ag⁺ ions by trisodium citrate. This is the first research reporting the synthesis of AgNS using only trisodium citrate as a reducing and stabilizing agent. The key elements of this original synthesis procedure are rapid hydrothermal synthesis of silver nanostars followed by a cooling down procedure by immersion in a water bath. The synthesis was performed in a sealed bottom flask homogenously heated and brought to a boil in a microwave oven. After 60 s, the colloidal solution was cooled down to room temperature by immersion in a water bath at 35 °C. The as-synthesized AgNS were washed by centrifugation and used for SERS analysis of test molecules (methylene blue) as well as biological analytes: pharmaceutical compounds with various Raman cross sections (doxorubicin, atenolol & metoprolol), cell lysates and amino acids (methionine & cysteine). UV-Vis absorption spectroscopy, (Scanning) Transmission Electron Microscopy ((S)TEM) and Atomic Force Microscopy (AFM) have been employed for investigating nanostars’ physical properties.     

Enhanced chain dynamics in loop-sorting-systems by means of layout optimization and a kinematic model of the polygon action

Poor dynamics owing to polygon action is a known concern in mechanical applications of closed articulated chains. In this paper a kinematic model of the polygon action in large chains of loop-sorting-systems is proposed. Through optimization techniques the chain dynamics is improved by minimizing the polygon action using a parametric model of the track layout as design variables. Three formulations of the kinematic polygon action are tested on an average sized planer tracks layout to find a superior model. Verification of the proposed optimization method is performed using a state-of-the-art multi-body simulation model of the chain dynamics.     

Survey of MRI Usefulness for the Clinical Assessment of Bone Microstructure

Bone microarchitecture has been shown to provide useful information regarding the evaluation of skeleton quality with an added value to areal bone mineral density, which can be used for the diagnosis of several bone diseases. Bone mineral density estimated from dual-energy X-ray absorptiometry (DXA) has shown to be a limited tool to identify patients’ risk stratification and therapy delivery. Magnetic resonance imaging (MRI) has been proposed as another technique to assess bone quality and fracture risk by evaluating the bone structure and microarchitecture. To date, MRI is the only completely non-invasive and non-ionizing imaging modality that can assess both cortical and trabecular bone in vivo. In this review article, we reported a survey regarding the clinically relevant information MRI could provide for the assessment of the inner trabecular morphology of different bone segments. The last section will be devoted to the upcoming MRI applications (MR spectroscopy and chemical shift encoding MRI, solid state MRI and quantitative susceptibility mapping), which could provide additional biomarkers for the assessment of bone microarchitecture.     

Variables related to premature terminations in a university counseling service: A reply to Saltzman's (1984) comment.

The authors respond to comments by C. Saltzman (see record 1984-30126-001) regarding their (see record 1983-11046-001) examination of variables related to premature termination in a university counseling service. Specifically discussed are Saltzman's concerns regarding the meaningfulness of the results, the citation of previous research, the definition of premature termination, and the operational definitions and procedures used. Issues involved in undertaking research using an existing data base and the influence of organizational/administrative factors on counseling process are also considered. (10 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

NMR,optical, and plastic flow experiments in bcc3He —4 He mixture crystals — in pursuit of a vacancy fluid

We describe experiments on the properties of bcc³He —⁴ He solid mixtures on the melting curve between 0.5K and 1.9K. In this paper we focus on effects related to the presence of thermal vacancies. First, we used NMR to image the³He distribution within the solid in equilibrium with the superfluid, as well as its T₁ and t₂. The most surprising result was that above about 1K, vacancy related motion of³He atoms in the solid becomes faster than in the liquid. To check the macroscopic aspects of this motion, we used the vibrating wire technique to look at plastic flow of the bcc solid phase, by moving the wire through the crystal. The temperature dependence of the plastic flow velocity indicates that the vacancy population in the bcc solid behaves like a viscous fluid. The extent to which the vacancy population causes the solid to have liquid like properties is best demonstrated through optical observations of the distillation of³He atoms out of the crystal, which takes place via formation of fluid bubbles within the solid, which then percolate into the liquid, creating a vivid impression of boiling.     

CAD model of effective dielectric constant of microstrip line on M-cut sapphire substrate

Simple and correct formulas in regard to frequency dispersion are derived for the calculation of an isotropic effective dielectric constant for the microstrip line on m-cut sapphire substrate. The formulas were verified by comparison to the results of full-wave analysis based on the equivalent surface impedance approach. The temperature dependence of the dielectric permittivity of sapphire is taken into account.     

Approximate mathematical models in high-speed hydrodynamics

Approximate solutions of some problems in high-speed hydrodynamics are given, the solutions being based upon well-known approaches, such as the principle of independence of cavity expansion (Logvinovich), formulation of the problem of the immersion of a solid contour into liquid (Wagner), various models of cavity closure in its tail, etc. Theoretical studies of the dynamic properties of slender ventilated cavities are performed. The mathematical model of a cavity is obtained in the form of a system of nonlinear time-delay differential equations. The linear theory of cavity stability and oscillations is developed for various cavity types. The mechanism of nonlinear cavity oscillations accounting for gas-bubble detachment is considered, and the results of extensive numerical experimentation are presented. A theoretical model of cavity closure is proposed that develops the well-known Efros approach with a re-entrant jet. An approximate analysis of the model has been performed. A planar problem of the impact and immersion of an expanding cylinder into liquid with a cylindrical free surface of variable radius is solved in Wagner’s formulation.     

Determination of fat in infant formula by robotic automated method

A method has been developed for the determination of fat in infant formula using a commercially available robotic system. The procedure and chemistry at large are the same as the manual method,Official Methods of Analysis 16.064, by the Association of Official Analytical Chemists (AOAC). Both liquid and powder forms of milk-protein-based and soy-protein-based matrices were analyzed in this study. The robotic operations are described in detail. The evaluation of the accuracy is accomplished by comparing the data obtained by the robotic automated method to those obtained by the official manual method. The analysis of variance does not indicate a statistically significant difference (p-value 0.0620, mean difference 0.0056%) between the mean results of the two methods for the milk-protein-based infant formula. The results of other matrices tested by both methods agreed within 1% relative of each other. The precision of the robotic automated method is slightly better than the manual method as shown by the overall relative standard deviation (RSD) of 0.167% vs 0.269%. The ruggedness of the instrument has been satisfactory. The results of this study suggest that the robotic automated method is suitable for this application.