Periodic solutions of differential equations with time lag containing a small parameter

Periodic solutions of differential equations with time lag containing small paramete

Adaptively Optimised Adaptive Importance Samplers

We introduce a new class of adaptive importance samplers leveraging adaptive optimisation tools, which we term AdaOAIS. We build on Optimised Adaptive Importance Samplers (OAIS), a class of techniques that adapt proposals to improve the mean-squared error of the importance sampling estimators by parameterising the proposal and optimising the $\chi^2$-divergence between the target and the proposal. We show that a naive implementation of OAIS using stochastic gradient descent may lead to unstable estimators despite its convergence guarantees. To remedy this shortcoming, we instead propose to use adaptive optimisers (such as AdaGrad and Adam) to improve the stability of the OAIS. We provide convergence results for AdaOAIS in a similar manner to OAIS. We also provide empirical demonstration on a variety of examples and show that AdaOAIS lead to stable importance sampling estimators in practice.Comment: This work has been submitted to the IEEE for possible publication. Copyright may be transferred without notice, after which this version may no longer be accessibl

Obesity Induces Hypothalamic Endoplasmic Reticulum Stress and Impairs Proopiomelanocortin (POMC) Post-translational Processing

It was shown previously that abnormal prohormone processing or inactive proconverting enzymes that are responsible for this processing cause profound obesity. Our laboratory demonstrated earlier that in the diet-induced obesity (DIO) state, the appetite-suppressing neuropeptide -melanocyte-stimulating hormone ( -MSH) is reduced, yet the mRNA of its precursor protein proopiomelanocortin (POMC) remained unaltered. It was also shown that the DIO condition promotes the development of endoplasmic reticulum (ER) stress and leptin resistance. In the current study, using an in vivo model combined with in vitro experiments, we demonstrate that obesity-induced ER stress obstructs the post-translational processing of POMC by decreasing proconverting enzyme 2, which catalyzes the conversion of adrenocorticotropin to -MSH, thereby decreasing -MSH peptide production. This novel mechanism of ER stress affecting POMC processing in DIO highlights the importance of ER stress in regulating central energy balance in obesity.Fil: Cakir, Isin. Brown University; Estados UnidosFil: Cyr, Nicole E.. Brown University; Estados UnidosFil: Perello, Mario. Brown University; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Litvinov, Bogdan Patedakis. Brown University; Estados UnidosFil: Romero, Amparo. Brown University; Estados UnidosFil: Stuart, Ronald C.. Brown University; Estados UnidosFil: Nillni, Eduardo A.. Brown University; Estados Unido

Research in the general area of non-linear dynamical systems Final report, 8 Jun. 1965 - 8 Jun. 1967

Nonlinear dynamical systems research on systems stability, invariance principles, Liapunov functions, and Volterra and functional integral equation

Effects of Local Weather Variation on Water-column Stratification and Hypoxia in the Western, Sandusky, and Central Basins of Lake Erie

Hypoxia, low dissolved oxygen (DO) concentrations (<2 mg/L), has been a major issue in Lake Erie for decades. While much emphasis has been placed on biological factors, particularly algal blooms, contributing to hypolimnetic oxygen depletion, there has been little focus on the role of weather. For this study, we monitored water temperature and DO concentrations at sites in the western, central, and Sandusky basins in Lake Erie during June and July 2010–2012. We then compared trends in stratification and DO concentrations to weather patterns during that period. We found that during those three years, there was significant variation in weather patterns, particularly decreased ice coverage and increased storm events in 2012. These weather patterns corresponded to 2012 having the warmest water temperatures, some of the lowest DO concentrations, and a deeper and thinner hypolimnion (especially in the central basin) than the previous years. We found a relationship between weather and hypoxia, providing further evidence for why these basins are susceptible to low DO conditions during summer months. The role of weather in hypoxia is another indication that the lake is vulnerable to effects of climate change and should be considered in management strategies

Theoretical and Experimental Studies of Schottky Diodes That Use Aligned Arrays of Single Walled Carbon Nanotubes

We present theoretical and experimental studies of Schottky diodes that use aligned arrays of single walled carbon nanotubes. A simple physical model, taking into account the basic physics of current rectification, can adequately describe the single-tube and array devices. We show that for as grown array diodes, the rectification ratio, defined by the maximum-to-minimum-current-ratio, is low due to the presence of m-SWNT shunts. These tubes can be eliminated in a single voltage sweep resulting in a high rectification array device. Further analysis also shows that the channel resistance, and not the intrinsic nanotube diode properties, limits the rectification in devices with channel length up to ten micrometer.Comment: Nano Research, 2010, accepte

Ghrelin Indirectly Activates Hypophysiotropic CRF Neurons in Rodents

Ghrelin is a stomach-derived hormone that regulates food intake and neuroendocrine function by acting on its receptor, GHSR (Growth Hormone Secretagogue Receptor). Recent evidence indicates that a key function of ghrelin is to signal stress to the brain. It has been suggested that one of the potential stress-related ghrelin targets is the CRF (Corticotropin-Releasing Factor)-producing neurons of the hypothalamic paraventricular nucleus, which secrete the CRF neuropeptide into the median eminence and activate the hypothalamic-pituitary-adrenal axis. However, the neural circuits that mediate the ghrelin-induced activation of this neuroendocrine axis are mostly uncharacterized. In the current study, we characterized in vivo the mechanism by which ghrelin activates the hypophysiotropic CRF neurons in mice. We found that peripheral or intra-cerebro-ventricular administration of ghrelin strongly activates c-fos – a marker of cellular activation – in CRF-producing neurons. Also, ghrelin activates CRF gene expression in the paraventricular nucleus of the hypothalamus and the hypothalamic-pituitary-adrenal axis at peripheral level. Ghrelin administration directly into the paraventricular nucleus of the hypothalamus also induces c-fos within the CRF-producing neurons and the hypothalamic-pituitary-adrenal axis, without any significant effect on the food intake. Interestingly, dual-label immunohistochemical analysis and ghrelin binding studies failed to show GHSR expression in CRF neurons. Thus, we conclude that ghrelin activates hypophysiotropic CRF neurons, albeit indirectly

Neonatal overfeeding during lactation rapidly and permanently misaligns the hepatic circadian rhythm and programmes adult NAFLD

Childhood obesity is a strong risk factor for adult obesity, type 2 diabetes, and cardiovascular disease. The mechanisms that link early adiposity with late-onset chronic diseases are poorly characterised. We developed a mouse model of early adiposity through litter size reduction. Mice reared in small litters (SLs) developed obesity, insulin resistance, and hepatic steatosis during adulthood. The liver played a major role in the development of the disease. Objective: To gain insight into the molecular mechanisms that link early development and childhood obesity with adult hepatic steatosis and insulin resistance. Methods: We analysed the hepatic transcriptome (Affymetrix) of control and SL mice to uncover potential pathways involved in the long-term programming of disease in our model. Results: The circadian rhythm was the most significantly deregulated Gene Ontology term in the liver of adult SL mice. Several core clock genes, such as period 1e3 and cryptochrome 1e2, were altered in two-week-old SL mice and remained altered throughout their life course until they reached 4e6 months of age. Defective circadian rhythm was restricted to the periphery since the expression of clock genes in the hypothalamus, the central pacemaker, was normal. The period-cryptochrome genes were primarily entrained by dietary signals. Hence, restricting food availability during the light cycle only uncoupled the central rhythm from the peripheral and completely normalised hepatic triglyceride content in adult SL mice. This effect was accompanied by better re-alignment of the hepatic period genes, suggesting that they might have played a causal role in mediating hepatic steatosis in the adult SL mice. Functional downregulation of Per2 in hepatocytes in vitro confirmed that the period genes regulated lipid-related genes in part through peroxisome proliferator-activated receptor alpha (Ppara). Conclusions: The hepatic circadian rhythm matures during early development, from birth to postnatal day 30. Hence, nutritional challenges during early life may misalign the hepatic circadian rhythm and secondarily lead to metabolic derangements. Specific time-restricted feeding interventions improve metabolic health in the context of childhood obesity by partially re-aligning the peripheral circadian rhythm

Leaf yellowing of the wheat cultivar Mace in the absence of yellowspot disease

The wheat variety Mace is currently dominating the southern wheat growing regions of Australia. It is high yielding in most environments and resistant to many diseases including yellow spot (also known as tan spot). However, observations of foliar yellowing of Mace have recently been reported in the field. This has raised concerns over a possible breakdown of resistance to yellow spot, which is caused by the necrotrophic fungal pathogen Pyrenophora triticirepentis. West Australian field samples of yellowing Mace leaves were evaluated for P. triticirepentis infection, and this pathogen was determined to be absent. Instead, Alternaria spp. were isolated from the wheat leaves. Pathogenicity assays showed that the recovered Alternaria spp. were unable to cause disease symptoms on Mace. Furthermore, spontaneous foliar lesions were observed in Mace grown in the absence of pathogens. It is therefore likely that such yellowing is a physiological trait, which will not respond to fungicide application. A marginal impact on yield cannot be excluded