Geometrical computations explain projection patterns of long-range horizontal connections in visual cortex

Neurons in primary visual cortex respond selectively to oriented stimuli such as edges and lines. The long-range horizontal connections between them are thought to facilitate contour integration. While many physiological and psychophysical findings suggest that collinear or association field models of good continuation dictate particular projection patterns of horizontal connections to guide this integration process, significant evidence of interactions inconsistent with these hypotheses is accumulating. We first show that natural random variations around the collinear and association field models cannot account for these inconsistencies, a fact that motivates the search for more principled explanations. We then develop a model of long-range projection fields that formalizes good continuation based on differential geometry. The analysis implicates curvature(s) in a fundamental way, and the resulting model explains both consistent data and apparent outliers. It quantitatively predicts the (typically ignored) spread in projection distribution, its nonmonotonic variance, and the differences found among individual neurons. Surprisingly, and for the first time, this model also indicates that texture (and shading) continuation can serve as alternative and complementary functional explanations to contour integration. Because current anatomical data support both (curve and texture) integration models equally and because both are important computationally, new testable predictions are derived to allow their differentiation and identification.     

Molecular mechanisms and selection influence the generation of the human V lambda J lambda repertoire

To define the lambda light chain repertoire in humans, a single-cell PCR technique using genomic DNA obtained from individual peripheral B cells was employed. Of the 30 known functional V lambda genes, 23 were detected in either the nonproductive or productive repertoires. Specific V lambda genes, including 2A2, 2B2, 1G, and 4B, were overexpressed in the nonproductive repertoire, whereas some V lambda genes, such as 3R, 2A2, 2B2, 1C, 1G, and 1B, were overexpressed in the productive repertoire. Comparison of the nonproductive and productive repertoires indicated that no V lambda genes were positively selected, whereas a number of V lambda genes, including 4C, 1G, 5B, and 4B, were negatively regulated. All four of the functional J lambda segments were found in both repertoires, with J lambda 7 observed most often. Evidence of terminal deoxynucleotidyltransferase activity was noted in nearly 80% of nonproductive V lambda J lambda rearrangements, and exonuclease activity was apparent in the majority. Despite this, the mean CDR3 length was 30 base pairs in both productive and nonproductive repertoires, suggesting that it was tightly regulated at the molecular level. These results have provided new insights into the dimensions of the human V lambda repertoire and the influences that shape it.     

First Principles Investigation of Cold Curves of Metals

The rapid development of better high pressure experimental techniques combined with efficient and accurate density functional calculations of the structural properties of materials provide a new avenue to promote the study of materials at high pressures, which is currently based mostly on simple phenomenological modelling. The progress of experimental results into higher-pressure regimes represents a challenge to the phenomenological approaches, which can be addressed by carefully considered ab initio calculations. We present cold curves of several elements, calculated using different approximations of DFT and compare them with available experimental data. The comparison shows good agreement both in simple single phase and complex multi-phase cases. It suggests that DFT may be used to extrapolate high pressure behaviour of materials beyond the currently possible pressure range, with a robust estimate of the accuracy of the extrapolation based on various DFT implementations.     

User attitudes towards news content personalization

Personalizing news content requires to choose the appropriate depth of personalization and to assess the extent to which readers’ explicit expressions of interest in general and specific news topics can be used as the basis for personalization. A preliminary survey examined 117 respondents’ attitudes towards news content personalization and their interest in various news topics and subtopics. The second survey examined 23 participants’ declared and actual interests. Participants preferred personalization based on general news topics. Declared interest in general news topics adequately predicted the actual interests in some topics, while in others users’ interests differed between general news topics and subtopics. The variance in interest in items also differed among topics. Thus, different personalization methods should be used for different topics. For some, such as ‘Sports’, users show either high interest or no interest at all. In the latter case most articles related to the topic should be removed, with the exception of items that refer to unique events that may raise general interest according to the expressed interest. In other topics, such as ‘Science & Technology’, most users are interested in important articles, even if they are not interested in the general news topic. Here, the filtering technique should identify the important articles and present them to all readers. The results can be used to develop effective and simple personalization mechanisms which can be applied to the personalization of news, as well as to other domains.     

Pharmacokinetics and Pharmacodynamics of Anthocyanins after Administration of Tart Cherry Juice to Individuals with Gout

Scope

Tart cherries (TCs) contain high levels of anthocyanins that exert potent antioxidant and antiinflammatory effects and potentially benefit individuals with gout.

Methods and results

This study aims to quantitate the major anthocyanins in TC Juice Concentrate (TCJC) and identify the pharmacokinetic (PK) and pharmacodynamic (PD) parameters of the major anthocyanin cyanidin-3-glucosylrutinoside (C3GR). A PK-PD study enrolling human subjects with a history of gout is performed. Subjects are randomized to receive either 60 or 120 mL of TCJC. Anthocyanins are quantitated using liquid chromatography-mass spectroscopy (LCMS). Antioxidant and antiinflammatory mRNA expression is measured using real-time qPCR before and after the administration of TCJC. A population PK model (popPK) is fit to the experimental data, and an indirect PD model (IDR) is constructed in Monolix.

Conclusion

Of the bioavailable anthocyanins, C3GR achieves the highest plasma concentration in a dose-dependent manner. A popPK predicts anthocyanin exposure, and an IDR produces reasonable approximations of PD effects.     

Deficient interleukin-10 production by neonatal T cells does not explain their ineffectiveness at promoting neonatal B cell differentiation

Neonatal T cells are poor promoters of Ig secretion by neonatal B cells. Since IL-10 has been shown to play a role in B cell differentiation, we investigated the relationship of IL-10 production by neonatal T cells and their ability to provide B cell help. Neonatal CD4+(CD8-) T cells and adult naive CD4+ (CD8-/CD45RO-) T cells activated with immobilized anti-CD3 produced consistently less IL-10 than adult memory CD4+(CD8-/CD45RA-) T cells. Production of IL-10 by adult and neonatal T cells was dependent on IL-2, but was unaffected by supplemental IL-4. Despite diminished IL-10 production, supplemental IL-10 increased neonatal T cell-dependent Ig secretion only modestly, but did not increase Ig heavy chain isotype switching. This contrasted with the ability of IL-10 to enhance the secretion of all Ig isotypes by adult B cells stimulated in the presence of either IL-2 or IL-4. These results suggest that IL-10 can promote T cell-dependent Ig secretion but not Ig heavy chain isotype switching by neonatal B cells. However, deficient IL-10 production alone does not account for the poor ability of neonatal T cells to support neonatal B cell Ig production.