Inhibition of food intake in obese subjects by peptide YY3-36

Background: The gut hormone fragment peptide YY3-36 (PYY) reduces appetite and food intake when infused into subjects of normal weight. In common with the adipocyte hormone leptin, PYY reduces food intake by modulating appetite circuits in the hypothalamus. However, in obesity there is a marked resistance to the action of leptin, which greatly limits its therapeutic effectiveness. We investigated whether obese subjects were also resistant to the anorectic effects of PYY.Methods: We compared the effects of PYY infusion on appetite and food intake in 12 obese and 12 lean subjects in a double-blind, placebo-controlled, crossover study. The plasma levels of PYY, ghrelin, leptin, and insulin were also determined.Results: Caloric intake during a buffet lunch offered two hours after the infusion of PYY was decreased by 30 percent in the obese subjects (P<0.001) and 31 percent in the lean subjects (P<0.001). PYY infusion also caused a significant decrease in the cumulative 24-hour caloric intake in both obese and lean subjects. PYY infusion reduced plasma levels of the appetite-stimulatory hormone ghrelin. Endogenous fasting and postprandial levels of PYY were significantly lower in obese subjects (the mean [+/-SE] fasting PYY levels were 10.2+/-0.7 pmol per liter in the obese group and 16.9+/-0.8 pmol per liter in the lean group, P<0.001). Furthermore, the fasting PYY levels correlated negatively with the body-mass index (r=-0.84, P<0.001).Conclusions: We found that obese subjects were not resistant to the anorectic effects of PYY. Endogenous PYY levels were low in the obese subjects, suggesting that PYY deficiency may contribute to the pathogenesis of obesity

Probing the structure of Nucleons in Electromagbetic Interactions

Open problems in the study of the nucleon structure using electromagnetic probes are discussed. The focus is on experimental aspects in the regime of strong interaction QCD. Significant progress in our understanding of the nucleon structure in this domain of QCD may be expected in the first decade of the next millenium. This is due to major experimental and theoretical efforts currently underway in this field.Comment: 9 pages, 6 figures, plenary talk at PANIC9

Precision Crystal Calorimetry in High Energy Physics

Crystal Calorimetry is widely used in high energy physics because of its precision. Recent development in crystal technology identified two key issues to reach and maintain crystal precision: light response uniformity and calibration in situ. Crystal radiation damage is understood. While the damage in alkali halides is found to be caused by the oxygen/hydroxyl contamination, it is the structure defects, such as oxygen vacancies, cause damage in oxides.Comment: 8 pages with 13 eps Figures, RevTe

Hypothalamic actions of neuromedin U.

The central nervous system and gut peptide neuromedin U (NMU) inhibits feeding after intracerebroventricular injection. This study explored the hypothalamic actions of NMU on feeding and the hypothalamo-pituitary-adrenal axis. Intraparaventricular nucleus (intra-PVN) NMU dose-dependently inhibited food intake, with a minimum effective dose of 0.1 nmol and a robust effect at 0.3 nmol. Feeding inhibition was mapped by NMU injection into eight hypothalamic areas. NMU (0.3 nmol) inhibited food intake in the PVN (0-1 h, 59 ± 6.9% of the control value; P < 0.001) and arcuate nucleus (0-1 h, 76 ± 10.4% of the control value; P < 0.05). Intra-PVN NMU markedly increased grooming and locomotor behavior and dose-dependently increased plasma ACTH (0.3 nmol NMU, 24.8 ± 1.9 pg/ml; saline, 11.4 ± 1.0; P < 0.001) and corticosterone (0.3 nmol NMU, 275.4 ± 40.5 ng/ml; saline, 129.4 ± 25.0; P < 0.01). Using hypothalamic explants in vitro, NMU stimulated CRH (100 nM NMU, 5.9 ± 0.95 pmol/explant; basal, 3.8 ± 0.39; P < 0.01) and arginine vasopressin release (100 nM NMU, 124.5 ± 21.8 fmol/explant; basal, 74.5 ± 7.6; P < 0.01). Leptin stimulated NMU release (141.9 ± 20.4 fmol/explant; basal, 92.9 ± 9.4; P < 0.01). Thus, we describe a novel role for NMU in the PVN to stimulate the hypothalamo-pituitary-adrenal axis and locomotor and grooming behavior and to inhibit feeding

Neuromedin U partially mediates leptin-induced hypothalamo-pituitary adrenal (HPA) stimulation and has a physiological role in the regulation of the HPA axis in the rat.

Intracerebroventricular (ICV) administration of the hypothalamic neuropeptide neuromedin U (NMU) or the adipostat hormone leptin increases plasma ACTH and corticosterone. The relationship between leptin and NMU in the regulation of the hypothalamo-pituitary adrenal (HPA) axis is currently unknown. In this study, leptin (1 nM) significantly increased the release of CRH from ex vivo hypothalamic explants by 207 ± 8.4% (P < 0.05 vs. basal), an effect blocked by the administration of anti-NMU IgG. The ICV administration of leptin (10 μg, 0.625 nmol) increased plasma ACTH and corticosterone 20 min after injection [plasma ACTH (picograms per milliliter): vehicle, 63 ± 20, leptin, 135 ± 36, P < 0.05; plasma corticosterone (nanograms per milliliter): vehicle, 285 ± 39, leptin, 452 ± 44, P < 0.01]. These effects were partially attenuated by the prior administration of anti-NMU IgG. Peripheral leptin also stimulated ACTH release, an effect attenuated by prior ICV administration of anti-NMU IgG. We examined the diurnal pattern of hypothalamic NMU mRNA expression and peptide content, plasma leptin, and plasma corticosterone. The diurnal changes in hypothalamic NMU mRNA expression were positively correlated with hypothalamic NMU peptide content, plasma corticosterone, and plasma leptin. The ICV administration of anti-NMU IgG significantly attenuated the dark phase rise in corticosterone [corticosterone (nanograms per milliliter): vehicle, 493 ± 38; NMU IgG, 342 ± 47 (P < 0.05)]. These studies suggest that NMU may play a role in the regulation of the HPA axis and partially mediate leptin-induced HPA stimulation. Copyright © 2006 by The Endocrine Society

Hierarchical transfer learning for online recognition of compound actions

Recognising human actions in real-time can provide users with a natural user interface (NUI) enabling a range of innovative and immersive applications. A NUI application should not restrict users’ movements; it should allow users to transition between actions in quick succession, which we term as compound actions. However, the majority of action recognition researchers have focused on individual actions, so their approaches are limited to recognising single actions or multiple actions that are temporally separated. This paper proposes a novel online action recognition method for fast detection of compound actions. A key contribution is our hierarchical body model that can be automatically configured to detect actions based on the low level body parts that are the most discriminative for a particular action. Another key contribution is a transfer learning strategy to allow the tasks of action segmentation and whole body modelling to be performed on a related but simpler dataset, combined with automatic hierarchical body model adaption on a more complex target dataset. Experimental results on a challenging and realistic dataset show an improvement in action recognition performance of 16% due to the introduction of our hierarchical transfer learning. The proposed algorithm is fast with an average latency of just 2 frames (66ms) and outperforms state of the art action recognition algorithms that are capable of fast online action recognition

Users-Centric Adaptive Learning System Based on Interval Type-2 Fuzzy Logic for Massively Crowded E-Learning Platforms

Abstract Technological advancements within the educational sector and online learning promoted portable data-based adaptive techniques to influence the developments within transformative learning and enhancing the learning experience. However, many common adaptive educational systems tend to focus on adopting learning content that revolves around pre-black box learner modelling and teaching models that depend on the ideas of a few experts. Such views might be characterized by various sources of uncertainty about the learner response evaluation with adaptive educational system, linked to learner reception of instruction. High linguistic uncertainty levels in e-learning settings result in different user interpretations and responses to the same techniques, words, or terms according to their plans, cognition, pre-knowledge, and motivation levels. Hence, adaptive teaching models must be targeted to individual learners’ needs. Thus, developing a teaching model based on the knowledge of how learners interact with the learning environment in readable and interpretable white box models is critical in the guidance of the adaptation approach for learners’ needs as well as understanding the way learning is achieved. This paper presents a novel interval type-2 fuzzy logic-based system which is capable of identifying learners’ preferred learning strategies and knowledge delivery needs that revolves around characteristics of learners and the existing knowledge level in generating an adaptive learning environment. We have conducted a large scale evaluation of the proposed system via real-word experiments on 1458 students within a massively crowded e-learning platform. Such evaluations have shown the proposed interval type-2 fuzzy logic system’s capability of handling the encountered uncertainties which enabled to achieve superior performance with regard to better completion and success rates as well as enhanced learning compared to the non-adaptive systems, adaptive system versions led by the teacher, and type-1-based fuzzy based counterparts.</jats:p

Evolution favors protein mutational robustness in sufficiently large populations

BACKGROUND: An important question is whether evolution favors properties such as mutational robustness or evolvability that do not directly benefit any individual, but can influence the course of future evolution. Functionally similar proteins can differ substantially in their robustness to mutations and capacity to evolve new functions, but it has remained unclear whether any of these differences might be due to evolutionary selection for these properties. RESULTS: Here we use laboratory experiments to demonstrate that evolution favors protein mutational robustness if the evolving population is sufficiently large. We neutrally evolve cytochrome P450 proteins under identical selection pressures and mutation rates in populations of different sizes, and show that proteins from the larger and thus more polymorphic population tend towards higher mutational robustness. Proteins from the larger population also evolve greater stability, a biophysical property that is known to enhance both mutational robustness and evolvability. The excess mutational robustness and stability is well described by existing mathematical theories, and can be quantitatively related to the way that the proteins occupy their neutral network. CONCLUSIONS: Our work is the first experimental demonstration of the general tendency of evolution to favor mutational robustness and protein stability in highly polymorphic populations. We suggest that this phenomenon may contribute to the mutational robustness and evolvability of viruses and bacteria that exist in large populations