Minimax Rates for Nonparametric Specification Testing in Regression Models

We deal with the issue of testing the specification of a regression function. As a leading case, we consider testing for a pure noise model. We study the smallest local alternatives that can be detected asymptotically in a minimax sense. We propose a simple testing procedure that has asymptotic optimal minimax properties for regular alternatives. We then adapt this procedure to testing the specification of a nonlinear parametric regression model. As a by-product, we obtain the rate of the optimal smoothing parameter that ensures optimal minimax properties for the test. We show that, by contrast, non-smoothing tests, such as Bierens' (1982) integrated conditional moment test, have undesirable minimax properties.

Isotopic Analysis of Diet Specificity in the Chisel-toothed Kangaroo Rat, Dipodomys microps

Rapid changes in global climate have put many species at risk, particularly niche specialists. The Chisel-toothed kangaroo rat, Dipodomys microps, is thought to specialize on the desert shrub Atriplex confertifolia. Because of this close relationship, D. microps was presumed to have tracked the shrub as its distribution shifted south during the last glacial maximum. However, recent phylogeographic evidence shows that D. microps’ distribution did not shift, despite the environmental changes during the last glacial maximum, posing an interesting question: How did D. microps persist in place when the plant on which it specializes did not inhabit the area? Concentrations of stable isotopes found within D. microps bone collagen were used to explore diet variability in the species over the past 8,000 years. Average δ13C values through time indicated that D. microps is capable of consuming plants other than A. confertifolia and a comparison of δ15N values to sympatric species showed that D. microps could also be consuming animal protein. Analysis of body size indicated that populations of D. microps did not experience a shift in average body size through time, but instead responded to changing abiotic conditions by shifting its dietary niche, as indicated by fluctuating values of δ13C and δ15N through time. Understanding which species are capable of behavioral and/or physiological responses to changing climate will allow us to better predict the impacts of ongoing and future climate change

Smoothing Quantile Regressions

We propose to smooth the objective function, rather than only the indicator on the check function, in a linear quantile regression context. Not only does the resulting smoothed quantile regression estimator yield a lower mean squared error and a more accurate Bahadur-Kiefer representation than the standard estimator, but it is also asymptotically differentiable. We exploit the latter to propose a quantile density estimator that does not suffer from the curse of dimensionality. This means estimating the conditional density function without worrying about the dimension of the covariate vector. It also allows for two-stage efficient quantile regression estimation. Our asymptotic theory holds uniformly with respect to the bandwidth and quantile level. Finally, we propose a rule of thumb for choosing the smoothing bandwidth that should approximate well the optimal bandwidth. Simulations confirm that our smoothed quantile regression estimator indeed performs very well in finite samples

Plant Vaccines: An Immunological Perspective.

The advent of technologies to express heterologous proteins in planta has led to the proposition that plants may be engineered to be safe, inexpensive vehicles for the production of vaccines and possibly even vectors for their delivery. The immunogenicity of a variety of antigens of relevance to vaccination expressed in different plants has been assessed. The purpose of this article is to examine the utility of plant-expression systems in vaccine development from an immunological perspective

Gastric stimulation: influence of electrical parameters on gastric emptying in control and diabetic rats

BACKGROUND: The aim of this study was to test the effect of different pulse frequencies and amplitudes during gastric stimulation (GS) on gastric emptying in the rat. METHODS: GS was performed in 2 groups of laparotomized rats: healthy control animals, and rats with acute diabetes. The effects of four pulse frequencies (0.5, 1, 10, 20 Hz) and three pulse amplitudes (5, 20, 40 mA) were tested. The volumes emptied from the stomach after the oro-gastric instillation of a nutrient solution were compared to those obtained in animals without GS. Intragastric pH values were assessed under basal conditions and after GS. RESULTS: In both groups, GS increased emptied volumes compared to conditions without stimulation (p < 0.05) for pulse frequencies above 0.5 Hz. Increases in pulse frequencies accelerated gastric emptying (p < 0.01) with a plateau at around 10 Hz. The increase in pulse amplitudes resulted in larger emptied volumes only when the pulse frequency was 1 Hz (p < 0.04) while the opposite effect was observed at 20 Hz (p < 0.04). The most effective combinations to enhance gastric emptying compared to baseline conditions were 10 Hz with 5 or 20 mA. The overall effect of GS on gastric emptying compared to baseline conditions without stimulation, was greater in diabetic than in controls rats (p < 0.05). During stimulation, intragastric pH values were not different from basal conditions during fasting or after a meal in control and diabetic rats. CONCLUSIONS: Although both pulse frequency and amplitude should be considered during GS, frequency appears to be the most critical point. The possibility of increasing gastric emptying by electrical stimulation in diabetic rats suggests potential clinical applications for this method

Zinc-Alpha 2-Glycoprotein Gene Expression in Adipose Tissue Is Related with Insulin Resistance and Lipolytic Genes in Morbidly Obese Patients

10.1371/journal.pone.003326

Coffee and tea consumption in relation to inflammation and basal glucose metabolism in a multi-ethnic Asian population: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Higher coffee consumption has been associated with a lower risk of type 2 diabetes in cohort studies, but the physiological pathways through which coffee affects glucose metabolism are not fully understood. The aim of this study was to evaluate the associations between habitual coffee and tea consumption and glucose metabolism in a multi-ethnic Asian population and possible mediation by inflammation.</p> <p>Methods</p> <p>We cross-sectionally examined the association between coffee, green tea, black tea and Oolong tea consumption and glycemic (fasting plasma glucose, HOMA-IR, HOMA-beta, plasma HbA1c) and inflammatory (plasma adiponectin and C-reactive protein) markers in a multi-ethnic Asian population (N = 4139).</p> <p>Results</p> <p>After adjusting for multiple confounders, we observed inverse associations between coffee and HOMA-IR (percent difference: - 8.8% for ≥ 3 cups/day versus rarely or never; <it>P_trend</it>= 0.007), but no significant associations between coffee and inflammatory markers. Tea consumption was not associated with glycemic markers, but green tea was inversely associated with plasma C-reactive protein concentrations (percent difference: - 12.2% for ≥ 1 cup/day versus < 1 cup/week; <it>P_trend</it>= 0.042).</p> <p>Conclusions</p> <p>These data provide additional evidence for a beneficial effect of habitual caffeinated coffee consumption on insulin sensitivity, and suggest that this effect is unlikely to be mediated by anti-inflammatory mechanisms.</p

Linear and Branched Glyco-Lipopeptide Vaccines Follow Distinct Cross-Presentation Pathways and Generate Different Magnitudes of Antitumor Immunity

Glyco-lipopeptides, a form of lipid-tailed glyco-peptide, are currently under intense investigation as B- and T-cell based vaccine immunotherapy for many cancers. However, the cellular and molecular mechanisms of glyco-lipopeptides (GLPs) immunogenicity and the position of the lipid moiety on immunogenicity and protective efficacy of GLPs remain to be determined.We have constructed two structural analogues of HER-2 glyco-lipopeptide (HER-GLP) by synthesizing a chimeric peptide made of one universal CD4(+) epitope (PADRE) and one HER-2 CD8(+) T-cell epitope (HER(420-429)). The C-terminal end of the resulting CD4-CD8 chimeric peptide was coupled to a tumor carbohydrate B-cell epitope, based on a regioselectively addressable functionalized templates (RAFT), made of four alpha-GalNAc molecules. The resulting HER glyco-peptide (HER-GP) was then linked to a palmitic acid moiety, attached either at the N-terminal end (linear HER-GLP-1) or in the middle between the CD4+ and CD8+ T cell epitopes (branched HER-GLP-2). We have investigated the uptake, processing and cross-presentation pathways of the two HER-GLP vaccine constructs, and assessed whether the position of linkage of the lipid moiety would affect the B- and T-cell immunogenicity and protective efficacy. Immunization of mice revealed that the linear HER-GLP-1 induced a stronger and longer lasting HER(420-429)-specific IFN-gamma producing CD8(+) T cell response, while the branched HER-GLP-2 induced a stronger tumor-specific IgG response. The linear HER-GLP-1 was taken up easily by dendritic cells (DCs), induced stronger DCs maturation and produced a potent TLR- 2-dependent T-cell activation. The linear and branched HER-GLP molecules appeared to follow two different cross-presentation pathways. While regression of established tumors was induced by both linear HER-GLP-1 and branched HER-GLP-2, the inhibition of tumor growth was significantly higher in HER-GLP-1 immunized mice (p<0.005).These findings have important implications for the development of effective GLP based immunotherapeutic strategies against cancers