Demonstration of functional coupling between dopamine synthesis and its packaging into synaptic vesicles

This is the publisher's version, also available electronically from "http://link.springer.com".We have previously shown that the membrane-associated form of the GABA-synthesizing enzyme, glutamate decarboxylase 65 (GAD65), is activated by synaptic vesicle proton gradient-mediated protein phosphorylation. We now report that the rate-limiting enzyme in dopamine (DA) biosynthesis, tyrosine hydroxylase (TH), is regulated similarly to GAD65. The membrane-associated form of TH (MTH) was activated by conditions favoring protein phosphorylation (e.g. ATP) and was inhibited by phosphatase (e.g. calf intestine phosphatase). Furthermore, the ATP-mediated activation of MTH was abolished by conditions that disrupted the proton gradient of synaptic vesicles, e.g. the presence of carbonyl cyanidem-chorophenylhydrazone, gramicidin, or the V-type ATPase inhibitor (bafilomycin), but not the P-type ATPase inhibitor (vanadate). Moreover, DA newly synthesized from tyrosine by MTH and membrane-associated aromatic amino acid decarboxylase was taken up preferentially rather than pre-existing DA. Therefore, the previously proposed model showing close coupling between GABA synthesis and GABA packaging into synaptic vesicles by vesicular GABA transporters is also applicable to the DA system. Hence, it is concluded that there is a general coupling mechanism between neurotransmitter synthesis and packaging of transmitter into synaptic vesicles

Micromechanics of thin oxide scale and surface roughness transfer in hot metal rolling

The deformation micromechanics of the thin oxide scale formed in hot metal rolling and surface roughness transfer characterization are very important for the quality of the finished product. Finite element simulation of the thin oxide scale deformation and surface roughness transfer is carried out. Surface asperity deformation of the thin oxide scale and strip is focused. Surface characterisation and micromechanics of the thin oxide scale deformation are obtained from the finite element simulation and experimental measurements. Simulation results are close to the measured values. The forming features of surface roughness transfer during hot metal rolling with lubrication are also discussed

Direct Interaction between AR and PAK6 in Androgen-Stimulated PAK6 Activation

A p21-activated kinase 6 (PAK6) was previously identified to be an androgen receptor (AR) interacting protein through a yeast two-hybrid screening. We used hormone responsive prostate cancer LAPC4 and LNCap cell lines as models to study the signaling events associated with androgen stimulation and PAK6. An androgen-stimulated PAK6 kinase activation was observed in LAPC4 cells expressing endogenous PAK6 and in LNCap cells ectopically expressing a wild type PAK6. This activation was likely mediated through a direct interaction between AR and PAK6 since siRNA knock-down of AR in LAPC4 cells downregulated androgen-stimulated PAK6 activation. In addition, LNCap cells expressing a non-AR-interacting PAK6 mutant exhibited dampened androgen-stimulated kinase activation. As a consequence of androgen-stimulated activation, PAK6 was phosphorylated at multiple serine/threonine residues including the AR-interacting domain of PAK6. Furthermore, androgen-stimulation promoted prostate cancer cell motility and invasion were demonstrated in LNCap cells ectopically expressing PAK6-WT. In contrast, LNCap expressing non-AR-interacting mutant PAK6 did not respond to androgen stimulation with increased cell motility and invasion. Our results demonstrate that androgen-stimulated PAK6 activation is mediated through a direct interaction between AR and PAK6 and PAK6 activation promotes prostate cancer cells motility and invasion

Road traffic flow forewarning and control model with the slope of the change rate

Zadnjih je godina točno i učinkovito kratkoročno predviđanje toka prometa u realnom vremenu jedna od ključnih tehnologija u ostvarenju upravljanja i reguliranja tokom cestovnog prometa iz ITS područja (Intelligent Transport System). Analizirajući postojeći model predviđanja toka prometa, predlaže se model za reguliranje cestovnog toka prometa, Model može pronaći nenormalnu točku analizom vremenskih serija toka prometa primjenom pada promjene brzine (slope change rate), i može analizirati taj trend promjena toka prometa u svrhu reguliranja toka prometa. Rezultati pokazuju da je algoritam pogodan za problem reguliranja vršnog cestovnog opterećenja prometa , a može biti učinkovit u reguliranju cestovnog prometa.Real-time, accurate and efficiency short term traffic flow prediction is one of the key technologies to realize traffic flow guidance and traffic control, which has been widely concerned in the domain of ITS (Intelligent Transport System) during recent years. Through the study of the existing traffic flow prediction model, road traffic flow control model with the slope of the change rate is proposed. The model can find out abnormal point from the traffic flow time series by the use of the slope change rate, and it can analyse this trend of traffic flow changes for control purposes of traffic flow. The achieved results indicate that the algorithm is suitable for road traffic flow peak control problem and could be effective for road traffic flow control

Enhancement of Efficiency and Lifetime of Blue Organic Light-Emitting Diodes Using Two Dopants in Single Emitting Layer

We have demonstrated efficient blue organic light-emitting diode with the structure of indium tin oxide/4,4′,4″-tris(N-(2-naphthyl)-N-phenyl-amino)triphenylamine/1,4-bis[N-(1-naphthyl)-N′-phenylamino]-4,4′-diamine/9,10-di(2-naphthyl)anthracene (ADN): 1-4-di-[4-(N,N-di-phenyl)amino]styryl-benzene (DSA-ph) 3 wt%/tris-(8-hydroxyquinoline)aluminum/LiF/Al. Improved efficiencies and longer operational lifetime were obtained by codoping a styrylamine-based dopant BD-3 (0.1 wt%) into the emitting layer of ADN doped with DSA-ph compared to the case of non-codoping. This was due to the improved charge balance and expansion of exciton recombination zone. The better charge balance was obtained by reducing the electron mobility of ADN which was higher than the hole mobility in the case of non-codoping

Development and validation of a dynamic online nomogram for predicting acute kidney injury in cirrhotic patients upon ICU admission

BackgroundAcute kidney injury (AKI) is one of the most common and deadly complications among cirrhotic patients at intensive care unit (ICU) admission. We aimed to develop and validate a simple and clinically useful dynamic nomogram for predicting AKI in cirrhotic patients upon ICU admission.MethodsWe analyzed the admission data of 4,375 patients with liver cirrhosis in ICU from 2008 to 2019 in the intensive care unit IV (MIMIC-IV) database. The eligible cirrhotic patients were non-randomly divided into derivation (n = 2,188) and validation (n = 2,187) cohorts at a ratio of 1:1, according to the order of admission. The least absolute shrinkage and selection operator regression model was used to identify independent predictors of AKI in the derivation cohort. A dynamic online nomogram was built using multivariate logistic regression analysis in the derivation cohort and then validated in the validation cohort. The C-index, calibration curve, and decision curve analysis were used to assess the nomogram’s discrimination, calibration, and clinical usefulness, respectively.ResultsThe incidence of AKI in 4,375 patients was 71.3%. Ascites, chronic kidney disease, shock, sepsis, diuretic drugs, hepatic encephalopathy, bacterial infections, vasoactive drugs, admission age, total bilirubin, and blood urea nitrogen were identified using the multivariate logistic regression analysis as significant predictors of AKI upon ICU admission. In the derivation cohort, the model showed good discrimination (C-index, 0.786; 95% CI, 0.765–0.806) and good calibration. The model in the validation cohort yielded good discrimination (C-index, 0.774; 95% CI, 0.753–0.795) and good calibration. Decision curve analysis demonstrated that the dynamic online nomogram was clinically useful.ConclusionOur study presents a dynamic online nomogram that incorporates clinical predictors and can be conveniently used to facilitate the individualized prediction of AKI in cirrhotic patients upon ICU admission

Toward Building a Physical Proxy for Gas-Phase Sulfuric Acid Concentration Based on Its Budget Analysis in Polluted Yangtze River Delta, East China

Gaseous sulfuric acid (H2SO4) is a crucial precursor for secondary aerosol formation, particularly for new particle formation (NPF) that plays an essential role in the global number budget of aerosol particles and cloud condensation nuclei. Due to technology challenges, global-wide and long-term measurements of gaseous H2SO4 are currently very challenging. Empirical proxies for H2SO4 have been derived mainly based on short-term intensive campaigns. In this work, we performed comprehensive measurements of H2SO4 and related parameters in the polluted Yangtze River Delta in East China during four seasons and developed a physical proxy based on the budget analysis of gaseous H2SO4. Besides the photo-oxidation of SO2, we found that primary emissions can contribute considerably, particularly at night. Dry deposition has the potential to be a non-negligible sink, in addition to condensation onto particle surfaces. Compared with the empirical proxies, the newly developed physical proxy demonstrates extraordinary stability in all the seasons and has the potential to be widely used to improve the understanding of global NPF fundamentally.Peer reviewe

Observational evidence for enhanced magnetic activity of superflare stars

Superflares are large explosive events on stellar surfaces one to six orders-of-magnitude larger than the largest flares observed on the Sun throughout the space age. Due to the huge amount of energy released in these superflares, it has been speculated if the underlying mechanism is the same as for solar flares, which are caused by magnetic reconnection in the solar corona. Here, we analyse observations made with the LAMOST telescope of 5,648 solar-like stars, including 48 superflare stars. These observations show that superflare stars are generally characterized by larger chromospheric emissions than other stars, including the Sun. However, superflare stars with activity levels lower than, or comparable to, the Sun do exist, suggesting that solar flares and superflares most likely share the same origin. The very large ensemble of solar-like stars included in this study enables detailed and robust estimates of the relation between chromospheric activity and the occurrence of superflares