Deep Submicron III-V on Si-Based Esaki Diode

Esaki tunneling diodes are reemerging as a viable technology option in helping to improve speed and performance of many high speed device applications. The revival of this technology may be linked to the development of new substrates available to research that allows for the fabrication of a device comparable to current silicon technology. Using a 111-V on Silicon Substrate, it was demonstrated that it is possible to create working Esaki Tunneling Diodes

Cardiac magnetic resonance assessment of central and peripheral vascular function in patients undergoing renal sympathetic denervation as predictor for blood pressure response

Background: Most trials regarding catheter-based renal sympathetic denervation (RDN) describe a proportion of patients without blood pressure response. Recently, we were able to show arterial stiffness, measured by invasive pulse wave velocity (IPWV), seems to be an excellent predictor for blood pressure response. However, given the invasiveness, IPWV is less suitable as a selection criterion for patients undergoing RDN. Consequently, we aimed to investigate the value of cardiac magnetic resonance (CMR) based measures of arterial stiffness in predicting the outcome of RDN compared to IPWV as reference. Methods: Patients underwent CMR prior to RDN to assess ascending aortic distensibility (AAD), total arterial compliance (TAC), and systemic vascular resistance (SVR). In a second step, central aortic blood pressure was estimated from ascending aortic area change and flow sequences and used to re-calculate total arterial compliance (cTAC). Additionally, IPWV was acquired. Results: Thirty-two patients (24 responders and 8 non-responders) were available for analysis. AAD, TAC and cTAC were higher in responders, IPWV was higher in non-responders. SVR was not different between the groups. Patients with AAD, cTAC or TAC above median and IPWV below median had significantly better BP response. Receiver operating characteristic (ROC) curves predicting blood pressure response for IPWV, AAD, cTAC and TAC revealed areas under the curve of 0.849, 0.828, 0.776 and 0.753 (p = 0.004, 0.006, 0.021 and 0.035). Conclusions: Beyond IPWV, AAD, cTAC and TAC appear as useful outcome predictors for RDN in patients with hypertension. CMR-derived markers of arterial stiffness might serve as non-invasive selection criteria for RDN

The p110 delta structure: mechanisms for selectivity and potency of new PI(3)K inhibitors.

Deregulation of the phosphoinositide-3-OH kinase (PI(3)K) pathway has been implicated in numerous pathologies including cancer, diabetes, thrombosis, rheumatoid arthritis and asthma. Recently, small-molecule and ATP-competitive PI(3)K inhibitors with a wide range of selectivities have entered clinical development. In order to understand the mechanisms underlying the isoform selectivity of these inhibitors, we developed a new expression strategy that enabled us to determine to our knowledge the first crystal structure of the catalytic subunit of the class IA PI(3)K p110 delta. Structures of this enzyme in complex with a broad panel of isoform- and pan-selective class I PI(3)K inhibitors reveal that selectivity toward p110 delta can be achieved by exploiting its conformational flexibility and the sequence diversity of active site residues that do not contact ATP. We have used these observations to rationalize and synthesize highly selective inhibitors for p110 delta with greatly improved potencies

Disrupted murine gut-to-human liver signaling alters bile acid homeostasis in humanized mouse liver models

The humanized liver mouse model is being exploited increasingly for human drug metabolism studies. However, its model stability, intercommunication between human hepatocytes and mouse nonparenchymal cells in liver and murine intestine, and changes in extrahepatic transporter and enzyme expressions have not been investigated. We examined these issues in FRGN [fumarylacetoacetate hydrolase (Fah2/2), recombination activating gene 2 (Rag22/2), and interleukin 2 receptor subunit gamma (IL-2rg 2/2) triple knockout] on nonobese diabetic (NOD) background] and chimeric mice: mFRGN and hFRGN (repopulated withmouse or human hepatocytes, respectively). hFRGN mice showed markedly higher levels of liver cholesterol, biliary bilirubin, and bile acids (liver, bile, and plasma; mainly human forms, but also murine bile acids) but lower transforming growth factor beta receptor 2 (TGFBR2) mRNA expression levels (10%) in human hepatocytes and other proliferative markers in mouse nonparenchymal cells (Tgf-1) and cholangiocytes [plasma membrane-bound, G protein-coupled receptor for bile acids (Tgr5)], suggestive of irregular regeneration processes in hFRGN livers. Changes in gene expression in murine intestine, kidney, and brain of hFRGN mice, in particular, induction of intestinal farnesoid X receptor (Fxr) genes: fibroblast growth factor 15 (Fgf15), mouse ileal bile acid binding protein (Ibabp), small heterodimer partner (Shp), and the organic solute transporter alpha (Osta), were observed. Proteomics revealed persistence of remnant murine proteins (cyotchrome P450 7α-hydroxylase (Cyp7a1) and other enzymes and transporters) in hFRGN livers and suggest the likelihood ofmouse activity.When comparedwith normal human liver tissue, hFRGN livers showed lower SHP mRNA and higher CYP7A1 (300%) protein expression, consequences of tb- and ta-muricholic acid-mediated inhibition of the FXR-SHP cascade and miscommunication between intestinal Fgf15 and human liver fibroblast growth factor receptor 4 (FGFR4), as confirmed by the unchanged hepatic pERK/total ERK ratio. Dysregulation of hepatocyte proliferation and bile acid homeostasis in hFRGN livers led to hepatotoxicity, gallbladder distension, liver deformity, and other extrahepatic changes, making questionable the use of the preparation for drug metabolism studies

Serum Concentrations of Myostatin and Myostatin-Interacting Proteins do not differ between young and Scarcopenic elderly men

Peer reviewedPostprin

Quadratic electronic response of a two-dimensional electron gas

The electronic response of a two-dimensional (2D) electron system represents a key quantity in discussing one-electron properties of electrons in semiconductor heterojunctions, on the surface of liquid helium and in copper-oxide planes of high-temperature superconductors. We here report an evaluation of the wave-vector and frequency dependent dynamical quadratic density-response function of a 2D electron gas (2DEG), within a self-consistent field approximation. We use this result to find the $Z_1^3$ correction to the stopping power of a 2DEG for charged particles moving at a fixed distance from the plane of the 2D sheet, $Z_1$ being the projectile charge. We reproduce, in the high-density limit, previous full nonlinear calculations of the stopping power of a 2DEG for slow antiprotons, and we go further to calculate the $Z_1^3$ correction to the stopping power of a 2DEG for a wide range of projectile velocities. Our results indicate that linear response calculations are, for all projectile velocities, less reliable in two dimensions than in three dimensions.Comment: 17 pages, 5 figures, to appear in Phys. Rev.

Happy Protest Voters: The Case of Rotterdam 1997–2009

Protest parties are on the rise in several European countries. This development is commonly attributed to a growing dissatisfaction with life and associated with declining quality of life in modern society of the lowest social strata. This explanation is tested in a cross-sectional analysis of voting and life-satisfaction in 63 districts of the city of Rotterdam in the Netherlands, where the share of protest voters increased from 10 % in 1994 to 31 % in 2009. Contrary to this explanation protest voting appeared not to be the most frequent in the least happy districts of Rotterdam, but in the medium happy segment. Also divergent from this explanation was that average happiness in city districts is largely independent of local living conditions, but is rather a matter of personal vulnerability in terms of education, income and health. These results fit alternative explanations in terms of mid

Multiferroicity in an organic charge-transfer salt: Electric-dipole-driven magnetism

Multiferroics, showing simultaneous ordering of electrical and magnetic degrees of freedom, are remarkable materials as seen from both the academic and technological points of view. A prominent mechanism of multiferroicity is the spin-driven ferroelectricity, often found in frustrated antiferromagnets with helical spin order. There, similar to conventional ferroelectrics, the electrical dipoles arise from an off-centre displacement of ions. However, recently a different mechanism, namely purely electronic ferroelectricity, where charge order breaks inversion symmetry, has attracted considerable interest. Here we provide evidence for this exotic type of ferroelectricity, accompanied by antiferromagnetic spin order, in a two-dimensional organic charge-transfer salt, thus representing a new class of multiferroics. Quite unexpectedly for electronic ferroelectrics, dipolar and spin order arise nearly simultaneously. This can be ascribed to the loss of spin frustration induced by the ferroelectric ordering. Hence, here the spin order is driven by the ferroelectricity, in marked contrast to the spin-driven ferroelectricity in helical magnets.Comment: 8 pages, 9 figures (including 4 pages and 6 figures in supplementary information). Version 2 with minor errors corrected (legend of Fig. 3c and definition of vectors e and Q

Future therapeutic targets in rheumatoid arthritis?

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by persistent joint inflammation. Without adequate treatment, patients with RA will develop joint deformity and progressive functional impairment. With the implementation of treat-to-target strategies and availability of biologic therapies, the outcomes for patients with RA have significantly improved. However, the unmet need in the treatment of RA remains high as some patients do not respond sufficiently to the currently available agents, remission is not always achieved and refractory disease is not uncommon. With better understanding of the pathophysiology of RA, new therapeutic approaches are emerging. Apart from more selective Janus kinase inhibition, there is a great interest in the granulocyte macrophage-colony stimulating factor pathway, Bruton's tyrosine kinase pathway, phosphoinositide-3-kinase pathway, neural stimulation and dendritic cell-based therapeutics. In this review, we will discuss the therapeutic potential of these novel approaches