Field Emission for resonance sensing in MEMS/NEMS

In the past decades, there is a considerable interest in the sensor community to move from micron to nano-devices, typically scaling of resonators such as cantilever beams

Transcriptomic Characterization of the Human Habenula Highlights Drug Metabolism and the Neuroimmune System

Due to size and accessibility, most information about the habenula is derived from rodent studies. To better understand the molecular signature of the habenula we characterized the genes that have high expression in the habenula. We compared anatomical expression profiles of three normal adult human brains and four fetal brains. We used gene set enrichment analyses to determine if genes annotated to specific molecular functions, cellular components, and biological processes are enriched in the habenula. We also tested gene sets related to depression and addiction to determine if they uniquely involve the habenula. As expected, we observed high habenular expression of GPR151, nicotinic cholinergic receptors, and cilia-associated genes (medial division). Genes identified in genetic studies of smoking and associated with nicotine response were enriched in the habenula. Genes associated with major depressive disorder did not have enriched expression in the habenula but genes negatively correlated with hedonic well-being were, providing a link to anhedonia. We observed enrichment of genes associated with diseases that are comorbid with addictions (hematopoiesis, thrombosis, liver cirrhosis, pneumonia, and pulmonary fibrosis) and depression (rheumatoid arthritis, multiple sclerosis, and kidney disease). These inflammatory diseases mark a neuroimmune signature that is supported by genes associated with mast cells, acute inflammatory response, and leukocyte migration. We also found enrichment of cytochrome p450 genes suggesting the habenula is uniquely sensitive to endogenous and xenobiotic compounds. Our results suggest the habenula receives negative reward signals from immune and drug processing molecules. This is consistent with the habenular role in the “anti-reward” system and suggests it may be a key bridge between autoimmune disorders, drug use, and psychiatric diseases

Analytic Metaphysics versus Naturalized Metaphysics: The Relevance of Applied Ontology

The relevance of analytic metaphysics has come under criticism: Ladyman & Ross, for instance, have suggested do discontinue the field. French & McKenzie have argued in defense of analytic metaphysics that it develops tools that could turn out to be useful for philosophy of physics. In this article, we show first that this heuristic defense of metaphysics can be extended to the scientific field of applied ontology, which uses constructs from analytic metaphysics. Second, we elaborate on a parallel by French & McKenzie between mathematics and metaphysics to show that the whole field of analytic metaphysics, being useful not only for philosophy but also for science, should continue to exist as a largely autonomous field

Response to highly active antiretroviral therapy among severely immuno-compromised HIV-infected patients in Cambodia.

BACKGROUND: HAART efficacy was evaluated in a real-life setting in Phnom Penh (Médecins Sans Frontières programme) among severely immuno-compromised patients. METHODS: Factors associated with mortality and immune reconstitution were identified using Cox proportional hazards and logistic regression models, respectively. RESULTS: From July 2001 to April 2005, 1735 patients initiated HAART, with median CD4 cell count of 20 (inter-quartile range, 6-78) cells/microl. Mortality at 2 years increased as the CD4 cell count at HAART initiation decreased, (4.4, 4.5, 7.5 and 24.7% in patients with CD4 cell count > 100, 51-100, 21-50 and < or = 20 cells/microl, respectively; P < 10). Cotrimoxazole and fluconazole prophylaxis were protective against mortality as long as CD4 cell counts remained < or = 200 and < or = 100 cells/microl, respectively. The proportion of patients with successful immune reconstitution (CD4 cell gain > 100 cells/microl at 6 months) was 46.3%; it was lower in patients with previous ART exposure [odds ratio (OR), 0.16; 95% confidence interval (CI), 0.05-0.45] and patients developing a new opportunistic infection/immune reconstitution infection syndromes (OR, 0.71; 95% CI, 0.52-0.98). Similar efficacy was found between the stavudine-lamivudine-nevirapine fixed dose combination and the combination stavudine-lamivudine-efavirenz in terms of mortality and successful immune reconstitution. No surrogate markers for CD4 cell change could be identified among total lymphocyte count, haemoglobin, weight and body mass index. CONCLUSION: Although CD4 cell count-stratified mortality rates were similar to those observed in industrialized countries for patients with CD4 cell count > 50 cells/microl, patients with CD4 cell count < or = 20 cells/microl posed a real challenge to clinicians. Widespread voluntary HIV testing and counselling should be encouraged to allow HAART initiation before the development of severe immuno-suppression

Contribution to the knowledge of the Cu–Sn–Zn system for compositions close to brass alloys

The effect of tin content in the equilibrium phases of the Cu–Zn-based alloys, within the range of chemical compositions with interest to brass producers is described. For this purpose, ternary alloys with copper contents between 55.4 and 67.5 wt.% and tin contents up to 5.30 wt.% have been studied. The chemical composition of each alloy has been determined by X-ray fluorescence spectrometry (XRF). Isothermal homogenization, followed by rapid cooling, has been employed to determine the equilibrium phases at different temperatures. The homogenized alloys have been observed by scanning electron microscopy and the respective chemical analysis of the phases determined by electron probe microanalysis (EPMA). The statistical analysis of the obtained results enable to correlate the chemical composition of equilibrium phases with temperature. The chemical composition of the three-phase field, for the studied temperatures, has also been determined

Bromodomains as therapeutic targets

Acetylation of lysine residues is a post-translational modification with broad relevance to cellular signalling and disease biology. Enzymes that ‘write’ (histone acetyltransferases, HATs) and ‘erase’ (histone deacetylases, HDACs) acetylation sites are an area of extensive research in current drug development, but very few potent inhibitors that modulate the ‘reading process’ mediated by acetyl lysines have been described. The principal readers of ɛ-N-acetyl lysine (Kac) marks are bromodomains (BRDs), which are a diverse family of evolutionary conserved protein-interaction modules. The conserved BRD fold contains a deep, largely hydrophobic acetyl lysine binding site, which represents an attractive pocket for the development of small, pharmaceutically active molecules. Proteins that contain BRDs have been implicated in the development of a large variety of diseases. Recently, two highly potent and selective inhibitors that target BRDs of the BET (bromodomains and extra-terminal) family provided compelling data supporting targeting of these BRDs in inflammation and in an aggressive type of squamous cell carcinoma. It is likely that BRDs will emerge alongside HATs and HDACs as interesting targets for drug development for the large number of diseases that are caused by aberrant acetylation of lysine residues

Green Tea Extract and (−)-Epigallocatechin-3-Gallate Inhibit Mast Cell-Stimulated Type I Collagen Expression in Keloid Fibroblasts via Blocking PI-3K/Akt Signaling Pathways

Keloid, a chronic fibro-proliferative disease, exhibits distinctive histological features characterized by an abundant extracellular matrix stroma, a local infiltration of inflammatory cells including mast cells (MCs), and a milieu of enriched cytokines. Previous studies have demonstrated that co-culture with MCs stimulate type I collagen synthesis in fibroblasts, but the signaling mechanisms remain largely unknown. In this study, we investigated the signaling pathways involved in MC-stimulated type I collagen synthesis and the effects of green tea extract (GTE) and its major catechin, (-)-epigallocatechin-3-gallate (EGCG), on collagen homeostasis in keloid fibroblasts. Our results showed that MCs significantly stimulated type I collagen expression in keloid fibroblasts, and the upregulation of type I collagen was significantly attenuated by blockade of phosphatidylinositol-3-kinase (PI-3K), mammalian target of rapamycin (mTOR), and p38 MAPK signaling pathways, but not by blockade of ERK1/2 pathway. Furthermore, GTE and EGCG dramatically inhibited type I collagen production possibly by interfering with the PI-3K/Akt/mTOR signaling pathway. Our findings suggest that interaction between MCs and keloid fibroblasts may contribute to excessive collagen accumulation in keloids and imply a therapeutic potential of green tea for the intervention and prevention of keloids and other fibrotic diseases. © 2006 The Society for Investigative Dermatology

Green Tea Extract and (−)-Epigallocatechin-3-Gallate Inhibit Mast Cell-Stimulated Type I Collagen Expression in Keloid Fibroblasts via Blocking PI-3K/Akt Signaling Pathways

Keloid, a chronic fibro-proliferative disease, exhibits distinctive histological features characterized by an abundant extracellular matrix stroma, a local infiltration of inflammatory cells including mast cells (MCs), and a milieu of enriched cytokines. Previous studies have demonstrated that co-culture with MCs stimulate type I collagen synthesis in fibroblasts, but the signaling mechanisms remain largely unknown. In this study, we investigated the signaling pathways involved in MC-stimulated type I collagen synthesis and the effects of green tea extract (GTE) and its major catechin, (-)-epigallocatechin-3-gallate (EGCG), on collagen homeostasis in keloid fibroblasts. Our results showed that MCs significantly stimulated type I collagen expression in keloid fibroblasts, and the upregulation of type I collagen was significantly attenuated by blockade of phosphatidylinositol-3-kinase (PI-3K), mammalian target of rapamycin (mTOR), and p38 MAPK signaling pathways, but not by blockade of ERK1/2 pathway. Furthermore, GTE and EGCG dramatically inhibited type I collagen production possibly by interfering with the PI-3K/Akt/mTOR signaling pathway. Our findings suggest that interaction between MCs and keloid fibroblasts may contribute to excessive collagen accumulation in keloids and imply a therapeutic potential of green tea for the intervention and prevention of keloids and other fibrotic diseases. © 2006 The Society for Investigative Dermatology