Genome-wide association study of peripheral neuropathy with D-drug-containing regimens in AIDS Clinical Trials Group protocol 384.

Stavudine (d4T) was, until recently, one of the most widely prescribed antiretroviral drugs worldwide. While there has been a major shift away from d4T use in resource-limited countries, a large number of patients have previously received (or continue to receive) d4T, and many have developed peripheral neuropathy. The identification of genetic predictors of increased risk might suggest novel therapeutic targets for such patients. In AIDS Clinical Trials Group protocol 384, antiretroviral-naïve patients were randomized to d4T/didanosine (ddI)- or zidovudine/lamivudine-containing regimens. Data from d4T/ddI recipients were analyzed for genome-wide associations (approximately 1 million genetic loci) with new onset distal sensory peripheral neuropathy. Analyses involved 254 patients (49 % White, 34 % Black, 17 % Hispanic), comprising 90 peripheral neuropathy cases (32 grade 1, 35 grade 2, 23 grade 3) and 164 controls. After correcting for multiple comparisons, no polymorphism was consistently associated with neuropathy among all patients, among White, Black, and Hispanic patients analyzed separately, both in genome-wide analyses (threshold, P < 5.0 × 10(-8)) and focused on 46 neuropathy-associated genes (threshold, P < 3.5 × 10(-5)). In the latter analyses, the lowest P values were in KIF1A among Whites (rs10199388, P = 8.4 × 10(-4)), in LITAF among Blacks (rs13333308, P = 6.0 × 10(-6)), and in NEFL among Hispanics (rs17763685, P = 5.6 × 10(-6)). Susceptibility to d4T/ddI-associated neuropathy is not explained by a single genetic variant with a marked effect

Boundary-crossing identities for diffusions having the time-inversion property

We review and study a one-parameter family of functional transformations, denoted by (S (β)) β∈ℝ, which, in the case β<0, provides a path realization of bridges associated to the family of diffusion processes enjoying the time-inversion property. This family includes Brownian motions, Bessel processes with a positive dimension and their conservative h-transforms. By means of these transformations, we derive an explicit and simple expression which relates the law of the boundary-crossing times for these diffusions over a given function f to those over the image of f by the mapping S (β), for some fixed β∈ℝ. We give some new examples of boundary-crossing problems for the Brownian motion and the family of Bessel processes. We also provide, in the Brownian case, an interpretation of the results obtained by the standard method of images and establish connections between the exact asymptotics for large time of the densities corresponding to various curves of each family

Modelling approaches to the dewetting of evaporating thin films of nanoparticle suspensions

We review recent experiments on dewetting thin films of evaporating colloidal nanoparticle suspensions (nanofluids) and discuss several theoretical approaches to describe the ongoing processes including coupled transport and phase changes. These approaches range from microscopic discrete stochastic theories to mesoscopic continuous deterministic descriptions. In particular, we describe (i) a microscopic kinetic Monte Carlo model, (ii) a dynamical density functional theory and (iii) a hydrodynamic thin film model. Models (i) and (ii) are employed to discuss the formation of polygonal networks, spinodal and branched structures resulting from the dewetting of an ultrathin ‘postcursor film’ that remains behind a mesoscopic dewetting front. We highlight, in particular, the presence of a transverse instability in the evaporative dewetting front, which results in highly branched fingering structures. The subtle interplay of decomposition in the film and contact line motion is discussed. Finally, we discuss a simple thin film model (iii) of the hydrodynamics on the mesoscale. We employ coupled evolution equations for the film thickness profile and mean particle concentration. The model is used to discuss the self-pinning and depinning of a contact line related to the ‘coffee-stain’ effect. In the course of the review we discuss the advantages and limitations of the different theories, as well as possible future developments and extensions

Extramedullary Hematopoiesis Generates Ly-6C(high) Monocytes That Infiltrate Atherosclerotic Lesions

BACKGROUND: Atherosclerotic lesions are believed to grow via the recruitment of bone marrow-derived monocytes. Among the known murine monocyte subsets, Ly-6C(high) monocytes are inflammatory, accumulate in lesions preferentially, and differentiate. Here we hypothesized that the bone marrow outsources the production of Ly-6C(high) monocytes during atherosclerosis. METHODS AND RESULTS: Using murine models of atherosclerosis and fate-mapping approaches, we show that hematopoietic stem and progenitor cells (HSPC) progressively relocate from the bone marrow to the splenic red pulp where they encounter GM-CSF and IL-3, clonally expand, and differentiate to Ly-6C(high) monocytes. Monocytes born in such extramedullary niches intravasate, circulate, and accumulate abundantly in atheromata. Upon lesional infiltration, Ly-6C(high) monocytes secrete inflammatory cytokines, reactive oxygen species, and proteases. Eventually, they ingest lipids and become foam cells. CONCLUSIONS: Our findings indicate that extramedullary sites supplement the bone marrow’s hematopoietic function by producing circulating inflammatory cells that infiltrate atherosclerotic lesions

The effect of temperature on adhesion forces between surfaces and model foods containing whey protein and sugar

The formation of fouling deposit from foods and food components is a severe problem in food processing and leads to frequent cleaning. The design of surfaces that resist fouling may decrease the need for cleaning and thus increase efficiency. Atomic force microscopy has been used to measure adhesion forces between stainless steel (SS) and fluoro-coated glass (FCG) microparticles and the model food deposits (i) whey protein (WPC), (ii) sweetened condensed milk, and (iii) caramel. Measurements were performed over a range of processing temperatures between 30 and 90 oC and at contact times up to 60 s. There is a significant increase in adhesion force of both types of microparticle to WPC at 90 oC for all contact times. For confectionary deposits adhesion to SS was similar. Adhesion of confectionary deposits to FCG at 30 oC revealed a decrease in adhesion compared to SS; at higher temperatures the adhesion forces were similar

Matching the nano- to the meso-scale: measuring deposit–surface interactions with atomic force microscopy and micromanipulation

Many researchers have studied the effects of changing the surface on fouling and cleaning. In biofouling the 'Baier curve' is a well-known result which relates adhesion to surface energy, and papers on the effect of changing surface energy to food fouling can be found more than 40 years ago. Recently the use of modified surfaces, at least at a research level, has been widespread. Here two different ways of studying surface-deposit interactions have been compared. Atomic force microscopy (AFM) is a method for probing interactions at a molecular level, and can measure (for example) the interaction between substrate and surfaces at a nm-scale. At a μm-mm level, we have developed a micromanipulation tool that can measure the force required to remove the deposit; the measure incorporates both surface and bulk deformation effects. The two methods have been compared by studying a range of model soils: toothpaste, as an example of a soil that can be removed by fluid flow alone, and confectionery soils. Removal has been studied from glass, stainless steel and fluorinated surfaces as examples of the sort of surfaces that can be found in practice. AFM measurements were made by using functionalized tips in force mode. The two types of probe give similar results, although the rheology of the soil affects the measurement from the micromanipulation probe under some circumstances. The data suggests that either method could be used to test candidate surfaces

Racetrack Inflation

We develop a model of eternal topological inflation using a racetrack potential within the context of type IIB string theory with KKLT volume stabilization. The inflaton field is the imaginary part of the K\"ahler structure modulus, which is an axion-like field in the 4D effective field theory. This model does not require moving branes, and in this sense it is simpler than other models of string theory inflation. Contrary to single-exponential models, the structure of the potential in this example allows for the existence of saddle points between two degenerate local minima for which the slow-roll conditions can be satisfied in a particular range of parameter space. We conjecture that this type of inflation should be present in more general realizations of the modular landscape. We also consider `irrational' models having a dense set of minima, and discuss their possible relevance for the cosmological constant problem.Comment: 23 pages 7 figures. The final version with minor modifications, to appear in JHE