A Neural Network of Adaptively Timed Reinforcement Learning and Hippocampal Dynamics

A neural model is described of how adaptively timed reinforcement learning occurs. The adaptive timing circuit is suggested to exist in the hippocampus, and to involve convergence of dentate granule cells on CA3 pyramidal cells, and NMDA receptors. This circuit forms part of a model neural system for the coordinated control of recognition learning, reinforcement learning, and motor learning, whose properties clarify how an animal can learn to acquire a delayed reward. Behavioral and neural data are summarized in support of each processing stage of the system. The relevant anatomical sites are in thalamus, neocortex, hippocampus, hypothalamus, amygdala, and cerebellum. Cerebellar influences on motor learning are distinguished from hippocampal influences on adaptive timing of reinforcement learning. The model simulates how damage to the hippocampal formation disrupts adaptive timing, eliminates attentional blocking, and causes symptoms of medial temporal amnesia. It suggests how normal acquisition of subcortical emotional conditioning can occur after cortical ablation, even though extinction of emotional conditioning is retarded by cortical ablation. The model simulates how increasing the duration of an unconditioned stimulus increases the amplitude of emotional conditioning, but does not change adaptive timing; and how an increase in the intensity of a conditioned stimulus "speeds up the clock", but an increase in the intensity of an unconditioned stimulus does not. Computer simulations of the model fit parametric conditioning data, including a Weber law property and an inverted U property. Both primary and secondary adaptively timed conditioning are simulated, as are data concerning conditioning using multiple interstimulus intervals (ISIs), gradually or abruptly changing ISis, partial reinforcement, and multiple stimuli that lead to time-averaging of responses. Neurobiologically testable predictions are made to facilitate further tests of the model.

Multi-parametric metabolic assessment of cells under stress conditions

Glycolysis, glutaminolysis, the Krebs cycle and oxidative phosphorylation are the main metabolic pathways. Exposing cells to key metabolic substrates (glucose, glutamine and pyruvate); investigation of the contribution of substrates in stress conditions such as uncoupling and hypoxia was conducted. Glycolysis, O2 consumption, O2 and ATP levels and hypoxia inducible factor (HIF) signalling in PC12 cells were investigated. Upon uncoupling with FCCP mitochondria were depolarised similarly in all cases, but a strong increase in respiration was only seen in the cells fed on glutamine with either glucose or pyruvate. Inhibition of glutaminolysis reversed the glutamine dependant effect. Differential regulation of the respiratory response to FCCP by metabolic environment suggests mitochondrial uncoupling has a potential for substrate-specific inhibition of cell function. At reduced O2 availability (4 % and 0 % O2), cell bioenergetics and local oxygenation varied depending on the substrate composition. Results indicate that both supply and utilisation of key metabolic substrates can affect the pattern of HIF-1/2α accumulation by differentially regulating iO2¬, ATP levels and Akt/Erk/AMPK pathways. Inhibition of key metabolic pathways can modulate HIF regulatory pathways, metabolic responses and survival of cancer cells in hypoxia. Hypoxia leads to transcriptional activation, by HIF, of pyruvate dehydrogenase (PDH) kinase which phosphorylates and inhibits PDH, a mitochondrial enzyme that converts pyruvate into acetyl-CoA. The levels of PDH (total and phosphorylated), PDH kinase and HIF-1α were analysed in HCT116 and HCT116 SCO2-/- (deficient in complex IV of the respiratory chain) grown under 20.9 % and 3 % O2. Data indicate that regulation of PDH can occur in a manner independent of the HIF-1/PDH kinase 1 axis, mitochondrial respiration and the demand for acetyl-CoA. Collectively these results can be applied to many diseases; reduced nutrient supply and O2 during ischemia/stroke, hypoglycaemia in diabetes mellitus and cancer associated changes in uncoupling protein expression levels.

Numerical simulation of heat transfer in rectangular microchannel

Numerical simulation of heat transfer in a high aspect ratio rectangular microchannel with heat sinks has been conducted, similar to an experimental study. Three channel heights measuring 0.3 mm, 0.6mmand 1mmare considered and the Reynolds number varies from 300 to 2360, based on the hydraulic diameter. Simulation starts with the validation study on the Nusselt number and the Poiseuille number variations along the channel streamwise direction. It is found that the predicted Nusselt number has shown very good agreement with the theoretical estimation, but some discrepancies are noted in the Poiseuille number comparison. This observation however is in consistent with conclusions made by other researchers for the same flow problem. Simulation continues on the evaluation of heat transfer characteristics, namely the friction factor and the thermal resistance. It is found that noticeable scaling effect happens at small channel height of 0.3 mm and the predicted friction factor agrees fairly well with an experimental based correlation. Present simulation further reveals that the thermal resistance is low at small channel height, indicating that the heat transfer performance can be enhanced with the decrease of the channel height.

Vibrational spectroscopy and DFT calculations of di-amino acid cyclic peptides. Part I: cyclo(Gly-Gly), cyclo(L-Ala-L-Ala) and cyclo(L-Ala-Gly) in the solid state and in aqueous solution

Investigations of the vibrational spectra of cyclo(Gly-Gly), cyclo(L-Ala-L-Ala) and cyclo(t-Ala-Gly) are reported. Raman scattering and Fourier transform infrared (FTIR) spectra of solid-state and aqueous protonated samples, as well as their corresponding N-deuterated isotopomers, have been examined. In addition, density functional theory (DFT) (B3-LYP/cc-pVDZ) calculations of molecular structures and their associated vibrational modes were carried out. In each case, the calculated structures of lowest energy for the isolated gas-phase molecules have boat conformations. Assignments have been made for the observed Raman and FTIR vibrational bands of the cyclic di-amino acid peptides (CDAPs) examined. Raman polarization studies of aqueous phase samples are consistent with C-2 and C-1 symmetries for the six-membered rings of cyclo(L-Ala-L-Ala) and cydo(L-Ala-Gly), respectively. There is a good correlation between experimental and calculated vibrational bands for the three CDAPs. These data are in keeping with boat conformations for cydo(L-Ala-L-Ala) and cyclo(L-Ala-Gly) molecules, predicted by the ab initio calculations, in both the solid and aqueous solution states. However, Raman spectroscopic results might infer that cyclo(L-AlaGly) deviates only slightly from planarity in the solid state. The potential energy distributions of the amide I and II modes of a cis-peptide linkage are shown to be significantly different from those of the trans-peptides. For example, deuterium shifts have shown that the cis-amide I vibrations found in cyclo(Gly-Gly), cyclo(L-Ala-L-Ala), and cyclo(L-Ala-Gly) have larger N-H contributions compared to their trans-amide counterparts. Compared to trans-amide II vibrations, cis-amide II vibrations show a considerable decrease in N-H character.

Non-local quantum gates: a cavity-quantum-electrodynamics implementation

The problems related to the management of large quantum registers could be handled in the context of distributed quantum computation: unitary non-local transformations among spatially separated local processors are realized performing local unitary transformations and exchanging classical communication. In this paper, a scheme is proposed for the implementation of universal non-local quantum gates such as a controlled NOT (CNOT) and a controlled quantum phase gate (CQPG). The system chosen for their physical implementation is a cavity-quantum-electrodynamics (CQED) system formed by two spatially separated microwave cavities and two trapped Rydberg atoms. The procedures to follow for the realization of each step necessary to perform a specific non-local operation are described.

Cancer incidence and mortality in patients with insulin-treated diabetes: a UK cohort study

Raised risks of several cancers have been found in patients with type II diabetes, but there are few data on cancer risk in type I diabetes. We conducted a cohort study of 28 900 UK patients with insulin-treated diabetes followed for 520 517 person-years, and compared their cancer incidence and mortality with national expectations. To analyse by diabetes type, we examined risks separately in 23 834 patients diagnosed with diabetes under the age of 30 years, who will almost all have had type I diabetes, and 5066 patients diagnosed at ages 30 - 49 years, who probably mainly had type II. Relative risks of cancer overall were close to unity, but ovarian cancer risk was highly significantly raised in patients with diabetes diagnosed under age 30 years ( standardised incidence ratio ( SIR) = 2.14; 95% confidence interval (CI) 1.22 - 3.48; standardised mortality ratio (SMR) = 2.90; 95% CI 1.45 - 5.19), with greatest risks for those with diabetes diagnosed at ages 10 - 19 years. Risks of cancer at other major sites were not substantially raised for type I patients. The excesses of obesity- and alcohol-related cancers in type II diabetes may be due to confounding rather than diabetes per se.

Robust face recognition with partial occlusion, illumination variation and limited training data by optimal feature selection

This study investigates face recognition with partial occlusion, illumination variation and their combination, assuming no prior information about the mismatch, and limited training data for each person. The authors extend their previous posterior union model (PUM) to give a new method capable of dealing with all these problems. PUM is an approach for selecting the optimal local image features for recognition to improve robustness to partial occlusion. The extension is in two stages. First, authors extend PUM from a probability-based formulation to a similarity-based formulation, so that it operates with as little as one single training sample to offer robustness to partial occlusion. Second, they extend this new formulation to make it robust to illumination variation, and to combined illumination variation and partial occlusion, by a novel combination of multicondition relighting and optimal feature selection. To evaluate the new methods, a number of databases with various simulated and realistic occlusion/illumination mismatches have been used. The results have demonstrated the improved robustness of the new methods.

SYSTOLIC IIR FILTERS WITH BIT LEVEL PIPELINING.

A novel bit-level systolic array architecture for implementing first-order IIR filter sections is presented. A latency of only two clock cycles is achieved by using a radix-4 redundant number representation, performing the recursive computation most-significant-digit first, and feeding back each digit of the result as soon as it is available.

Substrates modified by advanced glycation end-products cause dysfunction and death in retinal pericytes by reducing survival signals mediated by platelet-derived growth factor

AIMS/HYPOTHESIS: Premature death of retinal pericytes is a pathophysiological hallmark of diabetic retinopathy. Among the mechanisms proposed for pericyte death is exposure to AGE, which accumulate during diabetes. The current study used an in vitro model, whereby retinal pericytes were exposed to AGE-modified substrate and the mechanisms underlying pericyte death explored. METHODS: Pericytes were isolated from bovine retinal capillaries and propagated on AGE-modified basement membrane (BM) extract or non-modified native BM. The extent of AGE modification was analysed. Proliferative responses of retinal pericytes propagated on AGE-modified BM were investigated using a 5-bromo-2-deoxy-uridine-based assay. The effect of extrinsically added platelet-derived growth factor (PDGF) isoforms on these proliferative responses was also analysed alongside mRNA expression of the PDGF receptors. Apoptotic death of retinal pericytes grown on AGE-modified BM was investigated using terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling labelling, mitochondrial membrane depolarisation and by morphological assessment. We also measured both the ability of PDGF to reverse Akt dephosphorylation that was mediated by AGE-modified BM, and increased pericyte apoptosis. RESULTS: Retinal pericytes exposed to AGE-modified BM showed reduced proliferative responses in comparison to controls (p

Are food-related perceptions associated with meal portion size decisions? A cross-sectional study

The purpose of this study was to test a comprehensive model of meal portion size determinants consisting of sociodemographic, psychological and food-related variables, whilst controlling for hunger and thirst.
Using cross-sectional nationally representative data collected in 2075 participants from the Island of Ireland (IoI) and Denmark (DK), eight separate hierarchical multiple regression analyses were conducted to examine the association between food-related variables and meal portion size (i.e. pizza, vegetable soup, chicken salad and a pork meal) within each country. Stepwise regressions were run with physiological control measures (hunger and thirst) entered in the first step, sociodemographic variables (sex, age, body mass index (BMI)) in the second step; psychological variables (cognitive restraint, uncontrolled eating, emotional eating, general health interest (GHI)) in the third step and food-related variables (expected fillingness, liking, expected healthfulness, food familiarity) in the fourth step.
Sociodemographic variables accounted for 2-19% of the variance in meal portion sizes; psychological variables explained an additional 3-8%; and food-related variables explained an additional 2-12%. When all four variable groups were included in the regression models, liking and sometimes expected healthfulness was positively associated with meal portion size. The strongest association was for liking, which was statistically significant in both countries for all meal types. Whilst expected healthfulness was not associated with pizza portion size in either country, it was positively associated with meals that have a healthier image (vegetable soup; chicken salad and in IoI, the pork meal).
In conclusion, after considering sociodemographic and psychological variables, and the food-related variables of liking and expected healthfulness, there may be little merit in manipulating the satiating power, at least of these type of meals, to maintain or promote weight loss.
Keywords: Meal portion size; psychological variables; expected fillingness; expected healthfulness; food liking; food familiarity.

Trance psicadélico no Algarve: um estudo sobre as práticas culturais de um movimento marginal

Dissertação de mest., Comunicação, Cultura e Artes (Estudos Culturais), Faculdade de Ciências Humanas e Sociais, Univ. do Algarve, 2011