Betacellulin-Induced Beta Cell Proliferation and Regeneration Is Mediated by Activation of ErbB-1 and ErbB-2 Receptors

BACKGROUND: Betacellulin (BTC), a member of the epidermal growth factor family, is known to play an important role in regulating growth and differentiation of pancreatic beta cells. Growth-promoting actions of BTC are mediated by epidermal growth factor receptors (ErbBs), namely ErbB-1, ErbB-2, ErbB-3 and ErbB-4; however, the exact mechanism for beta cell proliferation has not been elucidated. Therefore, we investigated which ErbBs are involved and some molecular mechanisms by which BTC regulates beta cell proliferation. METHODOLOGY/PRINCIPAL FINDINGS: The expression of ErbB-1, ErbB-2, ErbB-3, and ErbB-4 mRNA was detected by RT-PCR in both a beta cell line (MIN-6 cells) and C57BL/6 mouse islets. Immunoprecipitation and western blotting analysis showed that BTC treatment of MIN-6 cells induced phosphorylation of only ErbB-1 and ErbB-2 among the four EGF receptors. BTC treatment resulted in DNA synthetic activity, cell cycle progression, and bromodeoxyuridine (BrdU)-positive staining. The proliferative effect was blocked by treatment with AG1478 or AG825, specific tyrosine kinase inhibitors of ErbB-1 and ErbB-2, respectively. BTC treatment increased mRNA and protein levels of insulin receptor substrate-2 (IRS-2), and this was blocked by the ErbB-1 and ErbB-2 inhibitors. Inhibition of IRS-2 by siRNA blocked cell cycle progression induced by BTC treatment. Streptozotocin-induced diabetic mice injected with a recombinant adenovirus expressing BTC and treated with AG1478 or AG825 showed reduced islet size, reduced numbers of BrdU-positive cells in the islets, and did not attain BTC-mediated remission of diabetes. CONCLUSIONS/SIGNIFICANCE: These results suggest that BTC exerts proliferative activity on beta cells through the activation of ErbB-1 and ErbB-2 receptors, which may increase IRS-2 expression, contributing to the regeneration of beta cells

High-aspect-ratio copper via filling used for three-dimensional chip stacking

Through-chip electrodes for three-dimensional packaging can offer short interconnection and reduced signal delay. Formation of suitable vias by electrodeposition into cavities presents a filling problem similar to that encountered in the damascene process. Because via dimensions for through-chip filling are larger and have a higher aspect ratio relative to features in damascene, process optimization requires modification of existing superconformal plating baths and plating parameters. In this study, copper filling of high-aspect-ratio through-chip vias was investigated and optimized with respect to plating bath composition and applied current wavetrain. Void-free vias 70 mu m deep and 10 mu m wide were formed in 60 min using additives in combination with pulse-reverse current and dissolved-oxygen enrichment. The effects of reverse current and dissolved oxygen on the performance of superfilling additives is discussed in terms of their effects on formation, destruction, and distribution of a Cu(I) thiolate accelerant. (c) 2005 The Electrochemical Society. All rights reserved. </p

On the Claims of Weak Block Synchronization in Bitcoin

Recent Bitcoin attacks [CCS\u2721, CCS\u2721, ICDCS\u2719] commonly exploit the phenomenon of so-called weak block synchronization in Bitcoin. The attacks use two independently-operated Bitcoin monitors — i.e., Bitnodes and a system of customized supernodes — to confirm that block propagation in Bitcoin is surprisingly slow. In particular, Bitnodes constantly reports that around 30% of nodes are 3 blocks (or more) behind the blockchain tip and the supernodes show that on average more than 60% of nodes do not receive the latest block even after waiting for 10 minutes. In this paper, we carefully re-evaluate these controversial claims with our own experiments in the live Bitcoin network and show that block propagation in Bitcoin is, in fact, fast enough (e.g., most peers we monitor receive new blocks in about 4 seconds) for its safety property. We identify several limitations and bugs of the two monitors, which have led to these inaccurate claims about the Bitcoin block synchronization. We finally ask several open-ended questions regarding the technical and ethical issues around monitoring blockchain networks

Long-term performance of a hybrid indirect evaporative cooling-mechanical vapor compression cycle: A case study in Saudi Arabia

In Saudi Arabia, air conditioning is the main consumer of electricity, and increasing its energy efficiency is of great importance for energy conservation and carbon footprint reduction. This study presents the evaluation of a hybrid indirect evaporative cooling-mechanical vapor compression (IEC-MVC) cycle for cooling applications in Saudi Arabia. Most cities in this country are characterized by a high sensible cooling demand, and a few cities near the coasts of the Red sea and the Persian Gulf also need dehumidification. By employing the hybrid system, IEC can undertake about 60% of the cooling load in the summer of arid cities, and energy consumption can be reduced by up to 50%. The contribution of IEC and energy saving are less significant in humid cities because the latent loads have to be handled by MVC. Over the whole year, IEC contributes 50% of the total cooling capacity and reduces energy consumption by 40% in dry cities, while the saving is lower at 15%–25% in humid cities like Mecca and Jeddah. The average water consumption of the IEC is in the range of 4–12 L/hr. The water consumption can be replenished by the condensate collected from the MVC evaporator if the ambient humidity is high. Based on the annual performance, the cost of the IEC-MVC process is calculated, and it is 15%–35% lower than the standalone MVC. The results demonstrate the great potential of the hybrid IEC-MVC cycle in Saudi Arabia

Comparisons of the Effects of Stent Eccentricity on the Neointimal Hyperplasia between Sirolimus-Eluting Stent versus Paclitaxel-Eluting Stent

PURPOSE: Previous studies suggested that asymmetric stent expansion did not affect suppression of neointimal hyperplasia (NIH) after sirolimus-eluting stents (SES) implantation. The aim of this study was to evaluate the effects of stent eccentricity (SE) on NIH between SES versus paclitaxel-eluting stents (PES) using an intravascular ultrasound (IVUS) analysis from the randomized trial. MATERIALS AND METHODS: Serial IVUS data were obtained from Post-stent Optimal Expansion (POET) trial, allocated randomly to SES or PES. Three different SE (minimum stent diameter divided by maximum stent diameter) were evaluated; SE at the lesion site with maximal %NIH area (SE-NIH), SE at the minimal stent CSA [SE-minimal stent area (SE-MSA)], and averaged SE through the entire stent (SE-mean). We classified each drug-eluting stents (DES) into the concentric (≥ mean SE) and eccentric groups (< mean SE) based on the mean value of SE. RESULTS: Among 301 enrolled patients, 233 patients [SES (n = 108), PES (n = 125)] underwent a follow-up IVUS. There was no significant correlation between %NIH area and SE-NIH (r = - 0.083, p = 0.391) or SE-MSA (r = - 0.109, p = 0.259) of SES. However, SE-NIH of PES showed a weak but significant correlation with %NIH area (r = 0.269, p < 0.01). As to the associations between SEmean and NIH volume index, SES revealed no significant correlation (r = - 0.001, p = 0.990), but PES showed a weak but significant correlation (r = 0.320, p < 0.01). However, there was no difference in the restenosis rate between the eccentric versus concentric groups of both DES. CONCLUSION: This study suggests that lower SE of both SES and PES, which means asymmetric stent expansion, may not be associated with increased NIH.ope

Observation of tW production in the single-lepton channel in pp collisions at root s=13 TeV

A measurement of the cross section of the associated production of a single top quark and a W boson in final states with a muon or electron and jets in proton-proton collisions at root s = 13 TeV is presented. The data correspond to an integrated luminosity of 36 fb(-1) collected with the CMS detector at the CERN LHC in 2016. A boosted decision tree is used to separate the tW signal from the dominant t (t) over bar background, whilst the subleading W+jets and multijet backgrounds are constrained using data-based estimates. This result is the first observation of the tW process in final states containing a muon or electron and jets, with a significance exceeding 5 standard deviations. The cross section is determined to be 89 +/- 4 (stat) +/- 12 (syst) pb, consistent with the standard model.Peer reviewe