Microring-Assisted Coupling Between Dissimilar Waveguides

The use of microring resonators to assist in the evanescent field coupling between dissimilar waveguides is proposed and analyzed. Theoretical analysis based on the coupled mode theory and nu-merical example show that complete cross power transfers can be obtained near the microring resonances. Applications of the device include power dividers, low-power thermo-optic or electro-optic switches, and modulators.     

UDP-glucose ceramide glucosyltransferase activates AKT,promoted proliferation,and doxorubicin resistance in breast cancer cells

The UDP-glucose ceramide glucosyltransferase (UGCG) is a key enzyme in the synthesis of glycosylated sphingolipids, since this enzyme generates the precursor for all complex glycosphingolipids (GSL), the GlcCer. The UGCG has been associated with several cancer-related processes such as maintaining cancer stem cell properties or multidrug resistance induction. The precise mechanisms underlying these processes are unknown. Here, we investigated the molecular mechanisms occurring after UGCG overexpression in breast cancer cells. We observed alterations of several cellular properties such as morphological changes, which enhanced proliferation and doxorubicin resistance in UGCG overexpressing MCF-7 cells. These cellular effects seem to be mediated by an altered composition of glycosphingolipid-enriched microdomains (GEMs), especially an accumulation of globotriaosylceramide (Gb3) and glucosylceramide (GlcCer), which leads to an activation of Akt and ERK1/2. The induction of the Akt and ERK1/2 signaling pathway results in an increased gene expression of multidrug resistance protein 1 (MDR1) and anti-apoptotic genes and a decrease of pro-apoptotic gene expression. Inhibition of the protein kinase C (PKC) and phosphoinositide 3 kinase (PI3K) reduced MDR1 gene expression. This study discloses how changes in UGCG expression impact several cellular signaling pathways in breast cancer cells resulting in enhanced proliferation and multidrug resistance.     

The conserved protein DCN-1/Dcn1p is required for cullin neddylation in C. elegans and S. cerevisiae

SCF-type E3 ubiquitin ligases are multi-protein complexes required for polyubiquitination and subsequent degradation of target proteins by the 26S proteasome. Cullins, together with the RING-finger protein Rbx1, form the catalytic core of the ligase, and recruit the substrate-recognition module. Cycles of covalent modification of cullins by the ubiquitin-like molecule Nedd8 (neddylation) and removal of Nedd8 by the COP9 signalosome (deneddylation) positively regulate E3 ligase activity. Here we report the identification and analysis of a widely conserved protein that is required for cullin neddylation in the nematode Caenorhabditis elegans and the yeast Saccharomyces cerevisiae. C. elegans DCN-1 and S. cerevisiae Dcn1p (defective in cullin neddylation) are characterized by a novel UBA-like ubiquitin-binding domain and a DUF298 domain of unknown function. Consistent with their requirements for neddylation, DCN-1 and Dcn1p directly bind Nedd8 and physically associate with cullins in both species. Moreover, overexpression of Dcn1p in yeast results in the accumulation of Nedd8-modified cullin Cdc53p. Both in vivo and in vitro experiments indicate that Dcn1p does not inhibit deneddylation of Cdc53p by the COP9 signalosome, but greatly increases the kinetics of the neddylation reaction.     

彩色多普勒超声在腹壁下动脉穿支选择中的应用

验证彩色多普勒超声对腹壁下动脉穿支血管术前探查的有效性,寻找腹壁下动脉穿支术前优势穿支的选择标准。利用彩色多普勒超声探查腹壁下动脉穿支皮瓣行乳房再造患者52例,重点记录穿支血管穿腹直肌前鞘点的体表投影、口径、血流信息,并通过分析比较以上信息,选择优势穿支。结果52例患者腹壁下动脉穿支穿腹直肌前鞘点于超声下均可显示,平均每侧下腹部3支,距脐平均(5.7±2.09)cm,其中条件适用于显微外科的穿支平均口径(0.95±0.32)cm,血流峰速平均约16.4 cm/s,阻力指数平均0.7。术中优势穿支采用率92.31%。说明高频彩色多普勒超声适用于腹壁下动脉穿支皮瓣术前血管探查,可精确指导穿支的术前选择,辅助手术方案制定以及皮瓣设计。     

Helium solubility in olivine and implications for high 3He/4He in ocean island basalts

High 3He/4He ratios found in ocean island basalts are the main evidence for the existence of an undegassed mantle reservoir. However, models of helium isotope evolution depend critically on the chemical behaviour of helium during mantle melting. It is generally assumed that helium is strongly enriched in mantle melts relative to uranium and thorium, yet estimates of helium partitioning in mantle minerals have produced conflicting results. Here we present experimental measurements of helium solubility in olivine at atmospheric pressure. Natural and synthetic olivines were equilibrated with a 50% helium atmosphere and analysed by crushing in vacuo followed by melting, and yield a minimum olivine-melt partition coefficient of 0.0025 +/- 0.0005 (s.d.) and a maximum of 0.0060 +/- 0.0007 (s.d.). The results indicate that helium might be more compatible than uranium and thorium during mantle melting and that high 3He/4He ratios can be preserved in depleted residues of melting. A depleted source for high 3He/4He ocean island basalts would resolve the apparent discrepancy in the relative helium concentrations of ocean island and mid-ocean-ridge basalts.     

The return of subducted continental crust in Samoan lavas

Substantial quantities of terrigenous sediments are known to enter the mantle at subduction zones, but little is known about their fate in the mantle. Subducted sediment may be entrained in buoyantly upwelling plumes and returned to the Earth's surface at hotspots, but the proportion of recycled sediment in the mantle is small, and clear examples of recycled sediment in hotspot lavas are rare. Here we report remarkably enriched 87Sr/86Sr and 143Nd/144Nd isotope signatures in Samoan lavas from three dredge locations on the underwater flanks of Savai'i island, Western Samoa. The submarine Savai'i lavas represent the most extreme 87Sr/86Sr isotope compositions reported for ocean island basalts to date. The data are consistent with the presence of a recycled sediment component (with a composition similar to the upper continental crust) in the Samoan mantle. Trace-element data show affinities similar to those of the upper continental crust--including exceptionally low Ce/Pb and Nb/U ratios--that complement the enriched 87Sr/86Sr and 143Nd/144Nd isotope signatures. The geochemical evidence from these Samoan lavas significantly redefines the composition of the EM2 (enriched mantle 2; ref. 9) mantle endmember, and points to the presence of an ancient recycled upper continental crust component in the Samoan mantle plume.     

A note on the predictive power of survey data in nowcasting euro area GDP

This paper investigates the trade‐off between timeliness and quality in nowcasting practices. This trade‐off arises when the frequency of the variable to be nowcast, such as gross domestic product (GDP), is quarterly, while that of the underlying panel data is monthly; and the latter contains both survey and macroeconomic data. These two categories of data have different properties regarding timeliness and quality: the survey data are timely available (but might possess less predictive power), while the macroeconomic data possess more predictive power (but are not timely available because of their publication lags). In our empirical analysis, we use a modified dynamic factor model which takes three refinements for the standard dynamic factor model of Stock and Watson (Journal of Business and Economic Statistics, 2002, 20, 147–162) into account, namely mixed frequency, preselections and cointegration among the economic variables. Our main finding from a historical nowcasting simulation based on euro area GDP is that the predictive power of the survey data depends on the economic circumstances; namely, that survey data are more useful in tranquil times, and less so in times of turmoil.     

WNK signalling pathways in blood pressure regulation

Hypertension (high blood pressure) is a major public health problem affecting more than a billion people worldwide with complications, including stroke, heart failure and kidney failure. The regulation of blood pressure is multifactorial reflecting genetic susceptibility, in utero environment and external factors such as obesity and salt intake. In keeping with Arthur Guyton’s hypothesis, the kidney plays a key role in blood pressure control and data from clinical studies; physiology and genetics have shown that hypertension is driven a failure of the kidney to excrete excess salt at normal levels of blood pressure. There is a number of rare Mendelian blood pressure syndromes, which have shed light on the molecular mechanisms involved in dysregulated ion transport in the distal kidney. One in particular is Familial hyperkalemic hypertension (FHHt), an autosomal dominant monogenic form of hypertension characterised by high blood pressure, hyperkalemia, hyperchloremic metabolic acidosis, and hypercalciuria. The clinical signs of FHHt are treated by low doses of thiazide diuretic, and it mirrors Gitelman syndrome which features the inverse phenotype of hypotension, hypokalemic metabolic alkalosis, and hypocalciuria. Gitelman syndrome is caused by loss of function mutations in the thiazide-sensitive Na/Cl cotransporter (NCC); however, FHHt patients do not have mutations in the SCL12A3 locus encoding NCC. Instead, mutations have been identified in genes that have revealed a key signalling pathway that regulates NCC and several other key transporters and ion channels in the kidney that are critical for BP regulation. This is the WNK kinase signalling pathway that is the subject of this review.