Reducing Reparameterization Gradient Variance

Optimization with noisy gradients has become ubiquitous in statistics and machine learning. Reparameterization gradients, or gradient estimates computed via the "reparameterization trick," represent a class of noisy gradients often used in Monte Carlo variational inference (MCVI). However, when these gradient estimators are too noisy, the optimization procedure can be slow or fail to converge. One way to reduce noise is to use more samples for the gradient estimate, but this can be computationally expensive. Instead, we view the noisy gradient as a random variable, and form an inexpensive approximation of the generating procedure for the gradient sample. This approximation has high correlation with the noisy gradient by construction, making it a useful control variate for variance reduction. We demonstrate our approach on non-conjugate multi-level hierarchical models and a Bayesian neural net where we observed gradient variance reductions of multiple orders of magnitude (20-2,000x)

New Target Genes for the Peroxisome Proliferator-Activated Receptor-γ (PPARγ) Antitumour Activity: Perspectives from the Insulin Receptor

The insulin receptor (IR) plays a crucial role in mediating the metabolic and proliferative functions triggered by the peptide hormone insulin. There is considerable evidence that abnormalities in both IR expression and function may account for malignant transformation and tumour progression in some human neoplasias, including breast cancer. PPARγ is a ligand-activated, nuclear hormone receptor implicated in many pleiotropic biological functions related to cell survival and proliferation. In the last decade, PPARγ agonists—besides their known action and clinical use as insulin sensitizers—have proved to display a wide range of antineoplastic effects in cells and tissues expressing PPARγ, leading to intensive preclinical research in oncology. PPARγ and activators affect tumours by different mechanisms, involving cell proliferation and differentiation, apoptosis, antiinflammatory, and antiangiogenic effects. We recently provided evidence that PPARγ and agonists inhibit IR by non canonical, DNA-independent mechanisms affecting IR gene transcription. We conclude that IR may be considered a new PPARγ “target” gene, supporting a potential use of PPARγ agonists as antiproliferative agents in selected neoplastic tissues that overexpress the IR

Influence of ewe feeding systems on carcass quality of suckling lambs

Numerous studies have evidenced significant differences in the carcass and meat quality of grass-fed and concentrate-fed lambs. The main differences regard carcass fatness (Murphy et al., 1994), subcutaneous fat colour (Prache and Theriez, 1999), meat colour (Priolo et al., 2002a) and fatty acid composition (Enser et al., 1998). The use of grazing in lamb feeding favours the presence of substances in the meat which are beneficial to human health. Different methods, based on the spectrophotometric properties of fat have been proposed to verify the origin of the product (Priolo et al., 2002b). The objective of the present study is to verify if and to what extent the carcass quality of suckling lambs is affected by ewe feeding systems

Electrochemical oxidation of water on synthetic boron-doped diamond thin film anodes

Electrolysis in aqueous 1 M HClO4 and 1 M H2SO4 solutions has been carried out under galvanostatic conditions using boron-doped diamond electrodes (BDD). Analyses of the oxidation products have shown that in 1 M HClO4 the main reaction is oxygen evolution, while in H2SO4 the main reaction is the formation of H2S2O8. In both electrolytes small amounts of O3 and H2O2 are formed. Finally, a simplified mechanism involving hydroxyl radicals formed by water discharge has been proposed for water oxidation on boron-doped diamond anode

A transcriptome analysis identifies molecular effectors of unconjugated bilirubin in human neuroblastoma SH-SY5Y cells

Background: The deposition of unconjugated bilirubin (UCB) in selected regions of the brain results in irreversible neuronal damage, or Bilirubin Encephalopathy (BE). Although UCB impairs a large number of cellular functions in other tissues, the basic mechanisms of neurotoxicity have not yet been fully clarified. While cells can accumulate UCB by passive diffusion, cell protection may involve multiple mechanisms including the extrusion of the pigment as well as pro-survival homeostatic responses that are still unknown. Results: Transcriptome changes induced by UCB exposure in SH-SY5Y neuroblastoma cell line were examined by high density oligonucleotide microarrays. Two-hundred and thirty genes were induced after 24 hours. A Gene Ontology (GO) analysis showed that at least 50 genes were directly involved in the endoplasmic reticulum (ER) stress response. Validation of selected ER stress genes is shown by quantitative RT-PCR. Analysis of XBP1 splicing and DDIT3/CHOP subcellular localization is presented. Conclusion: These results show for the first time that UCB exposure induces ER stress response as major intracellular homeostasis in surviving neuroblastoma cells in vitro