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

Manipulation of Rat Movement via Nigrostriatal Stimulation Controlled by Human Visually Evoked Potentials

Here, we report that the development of a brain-to-brain interface (BBI) system that enables a human user to manipulate rat movement without any previous training. In our model, the remotely-guided rats (known as ratbots) successfully navigated a T-maze via contralateral turning behaviour induced by electrical stimulation of the nigrostriatal (NS) pathway by a brain-computer interface (BCI) based on the human controller's steady-state visually evoked potentials (SSVEPs). The system allowed human participants to manipulate rat movement with an average success rate of 82.2% and at an average rat speed of approximately 1.9 m/min. The ratbots had no directional preference, showing average success rates of 81.1% and 83.3% for the left-and right-turning task, respectively. This is the first study to demonstrate the use of NS stimulation for developing a highly stable ratbot that does not require previous training, and is the first instance of a training-free BBI for rat navigation. The results of this study will facilitate the development of borderless communication between human and untrained animals, which could not only improve the understanding of animals in humans, but also allow untrained animals to more effectively provide humans with information obtained with their superior perception.11Ysciescopu

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

For Whom the Price Escalates: High Price and Uncertain Value of Cancer Drugs

The price of cancer drugs has skyrocketed, yet it is not clear whether their value is commensurate with their price. More cancer drugs are approved under expedited review, which considers less rigorous clinical evidence, yet only 20% of them show an overall survival gain in the confirmatory trial. Moreover, clinical data are often generated based on small, single-arm studies with surrogate outcomes, challenging economic evaluation. With their high price and uncertain (marginal) clinical value, cancer drugs are frequently rejected by health technology assessment (HTA) bodies. Therefore, agencies, including the UK’s National Institute for Health and Care Excellence (NICE), have adopted cancer drug funds (CDF) or risk-sharing schemes to provide extra access for expensive cancer drugs which fail to meet NICE’s cost effectiveness threshold. With rising pricing and fewer new cancer medications with novel mechanisms of action, it is unclear if newly marketed cancer therapies address unmet clinical needs or whether we are paying too much. Transparency, equity, innovativeness, and sustainability are all harmed by a “special” approach for cancer medications. If early access is allowed, confirmatory trials within a certain time frame and economic evaluation should be conducted, and label changes or disinvestment should be carried out based on those evaluations

Technical Trends Related to Intermodal Automated Freight Transport Systems (AFTS) *

In recent years, advanced countries including the US, Germany, the Netherlands and Japan have been actively developing automated intermodal freight transport system technology aimed at reducing greenhouse gas and fine dust, minimizing infrastructure costs and logistics costs, and mitigating traffic congestion have. The purpose of this study is to provide direction for the development of automated intermodal freight transport system by analyzing trends of related technology. Keywords: Automated Freight Transport Systems(AFTS), Freight Transport, Efficient Transport, Port and Inland Hub, Technology Tren

Projecting Lifetime Health Outcomes and Costs Associated with the Ambient Fine Particulate Matter Exposure among Adult Women in Korea

We sought to estimate the lifetime healthcare costs and outcomes associated with the exposure to the escalated concentration of fine particulate matter (particle size < 2.5 μm, PM2.5) among adult Korean women. We adapted a previously developed Markov model, and a hypothetical cohort composed of Korean women was exposed to either a standard (15 μg/m3) or increased (25 μg/m3) concentration of PM2.5. The time horizon of the analysis was 60 years, and the cycle length was 1 year. The outcomes were presented as direct healthcare costs and quality-adjusted life years (QALYs), and costs were discounted annually at 5%. Deterministic and probabilistic sensitivity analyses were performed. The model estimated that when the exposure concentration was increased by 10 μg/m3, the lifetime healthcare cost increased by USD 9309, which is an 11.3% increase compared to the standard concentration group. Women exposed to a higher concentration of PM2.5 were predicted to live 30.64 QALYs, compared to 32.08 QALYs for women who were exposed to the standard concentration of PM2.5. The tendency of a higher cost and shorter QALYs at increased exposure was consistent across a broad range of sensitivity analyses. The negative impact of PM2.5 was higher on cost than on QALYs and accelerated as the exposure time increased, emphasizing the importance of early intervention

Characteristics Analysis of Freight Mode Choice Model According to the Introduction of a New Freight Transport System

The purpose of this study is to identify the characteristics of freight mode choices made by shippers and carriers with the introduction of a new freight transport system. We set an area in which actual freight transport takes place as the analysis scope and performed a survey of the shippers and carriers that transport containers to identify their stated preference (SP) regarding the new freight mode. The SP survey was carried out through an experimental design and this study considered the three factors of transport time, transport cost, and service level. This study compared and analyzed the models by distance using an individual behavior model. The results of estimating the model showed that the explanatory power of the model classified by distance and the individual parameters have statistical significance. The hit ratio was also high, which confirms that the model was estimated properly. In addition, the range of elasticity and the value of travel time analyzed using the model were evaluated to be appropriate compared to previous studies. The findings of the elasticity analysis show that strategies for reducing the transport cost are effective to increase the demand for the new transport mode. The value of travel time of freight transport was found to be higher than the current value generally applied in Korea. Considering that the value of travel time currently used is based on road freight transport, further research is required to apply a new value of travel time that reflects the characteristics of the new transport mode in the future