Hepatocellular carcinoma (HCC) typically relies on angiogenesis for its malignant behavior, including growth and metastasis. Vasohibin 2 (VASH2) was previously identified as an angiogenic factor, but its role in tumorigenesis is unknown. Using quantitative PCR and western blot analyses, we found that VASH2 is overexpressed in HCC cells and tissues. Using chromatin immunoprecipitation, we detected histone modifications at the putative VASH2 promoter, with increased H3K4 trimethylation and H3 acetylation and decreased H3K27 trimethylation, suggesting that epigenetic mechanisms are responsible for the deregulated VASH2 transcription in HCC. Knockdown of VASH2 via siRNA inhibited the proliferation of the hepatoma cell lines by delaying cell cycle progression and increasing apoptosis. Importantly, we found VASH2 secreted in the culture supernatant, and co-expression of its secretory chaperone small vasohibin-binding protein (SVBP) further enhanced VASH2 secretion. The supernatant from HepG2 cells expressing VASH2 enhanced the proliferation, migration and tube formation of human umbilical vein endothelial cells, and knockdown of VASH2 significantly inhibited these effects. In an in vivo study using a nude mouse model, we found that exogenous VASH2 significantly contributed to tumor growth, microvessel density and hemoglobin concentration in the tumors. Further analyses showed that the VASH2-mediated increase in the transcription of fibroblast growth factor-2, vascular endothelial growth factor and vasohibin 1 may be the mechanism underlying these effects. Taken together, these data indicate that VASH2 is abnormally expressed in HCC cells as a result of histone modifications and that VASH2 contributes to the angiogenesis in HCC via an SVBP-mediated paracrine mechanism. These results indicate a novel and important role for VASH2 in HCC angiogenesis and malignant transformation.Oncogene advance online publication, 21 May 2012; doi:10.1038/onc.2012.177.

Recently, Østergaard and Zamir reveal the connection between multiple description coding and delta-sigma quantization (DSQ). The principle has been applied to image coding, with main focus on the framework where each block is processed separately. In this correspondence, we propose a twochannel multiple description image coding scheme which performs inter-block processing. The source image is first rearranged into a block sequence. Then, vector DSQ is performed with a bank of noise-shaping filters. Their coefficients as well as the quantization steps are chosen by a rate-distortion optimization algorithm. A post-processing algorithm is proposed for side decoding. Experiment results show the improvement achieved by the proposed scheme in terms of both PSNR values and subjective quality.

A double metal-layer thin-film platinum microelectrode array was fabricated for implantation between sclera and choroid based on MEMS processing techniques and photosensitive polyimide material. The array was composed of 60 stimulating sites (6 ~ 10) and four selectable returning electrodes. The diameter of each stimulating electrode was 350 Êm with a center-to-center spacing of 750 Êm. The transient voltage responses of the electrode to current pulse stimulation indicated a charge-injection capacity greater than 52.1 ÊC/cm2. Acute in vivo animal experiments showed that the implicit time of electrically evoked potentials (EEPs) was 17.09 } 1.45 ms at a threshold current of 25.55 } 5.43 ÊA for a full-row of simultaneously stimulated electrodes (i.e. current applied simultaneously to each of the 10 electrodes). Individual electrode stimulation threshold was 48.57 } 6.90 ÊA. The corresponding threshold charge densities were 13.28 } 2.82 ÊC/cm2 and 25.24 } 3.59 ÊC/cm2, respectively. The spatial spread of the maximally recorded P1 response in the EEPs indicated a correspondence between the retinal stimulation site and the focal response location in the cortex. This method of array fabrication is suitable for acute suprachoroidal stimulation, and has a potential use for the fabrication of a visual prosthesis.

Objective:To determine cord blood angiotensin II (Ang II) concentration and assess its relationship to fetal insulin sensitivity in the offspring of mothers with gestational diabetes mellitus (GDM) at birth.Study Design:Thirty women with GDM and 30 healthy women were evaluated at elective cesarean delivery. Cord blood was obtained for measurement of Ang II, glucose and insulin. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated and used to estimate fetal insulin sensitivity.Result:The offspring of mothers with GDM had higher ponderal index (PI), HOMA-IR and cord Ang II and insulin concentrations than the offspring of healthy mothers. Cord insulin concentration and HOMA-IR were positively associated with PI in all the offspring. Cord Ang II concentration was positively associated with HOMA-IR in the offspring of mothers with GDM.Conclusion:Increased cord Ang II concentration is associated with decreased insulin sensitivity in the offspring of mothers with GDM.Journal of Perinatology advance online publication, 12 April 2012; doi:10.1038/jp.2012.40.

AIM By means of comparing the 2009 staging with the 1994 staging for vulva carcinoma on prognostic predicting, the essay aims to investigate the alterations of clinical decision due to the staging changing. METHODS A retrospective analysis was adopted which involves 100 patients with primary squamous cell carcinoma of the vulva treated at Sun Yat-sen University Cancer Center from January 1980 to December 2005. Meanwhile, survival rate was calculated by life table method. In addition, Kaplan-Meirer method was used to evaluate the prognostic factors in univariate analysis. And the independent prognostic factors were provided through COX regression model. RESULTS Univariate analysis indicated that the prognostic factors of vulva squamous cell carcinoma were: age (P=0.018), lymph node metastasis (P=0.010), the 1988 staging (P=0.031), the 2009 staging (P=0.001), the number of positive lymphnodes (P<0.001), treatment method (P=0.011), recurrence site (P=0.024). COX regression model indicated that the independent prognostic factor was: the number of positive lymph nodes (P<0.001). Here was not significant difference in overall survival rate (P=0.454) between unilateral or bilateral lymph node metastasis. Also, lesion diameter was not an independent prognostic factor (P=0.380). CONCLUSION Compared with the 1994 staging, the 2009 staging made some modifications in lesion size, extension, lymph node status and so on. The 2009 staging is better than the 1994 staging on prognostic predicting and, which could guide the clinical treatment more accurately.

The glycogen synthase kinase 3 (GSK3) inhibitor, 6-bromoindirubin-3'-oxime (BIO), is a key regulator of many signaling pathways to maintain pluripotency of human and mouse embryonic stem cells (ESCs). However, the effect of BIO on derivation of dairy goat male germline stem cells (mGSCs) remains unclear. The objectives of this study were to investigate whether BIO influences derivation of dairy goat mGSCs. Dairy goat mGSCs were cultured in mTeSR containing BIO medium and its effects on the proliferation ability of goat mGSCs (derived from goats ≤2 mo of age) were evaluated by 5-Bromo-2-deoxyuridine (BrdU) incorporation and alkaline phosphatase (AP) staining. Furthermore, its effects on maintenance of the undifferentiated state of mGSCs in late passages of cultures, as well as the capacity of mGSCs to differentiate into embryoid bodies (EBs) were examined. The presence of BIO increased the mitosis index and the number of AP positive colonies, as well as expression of pluripotent markers, Oct4, Nanog, Sox2, C-myc, Klf4, E-cadherin, and the proliferative markers, Pcna and C-myc. In contrast, there was no significant change in expression of apoptosis markers, P53, P21 and cyclin-related genes (Cyclin A, CDK2, Cyclin D1), as determined by RT-PCR analysis. When mGSCs were cultured in mTeSR medium containing BIO, EBs were formed, which were capable of further differentiating into various cell types found in the three embryonic germ layers, as determined by immunofluorescence and/or histologic staining. In conclusion, adding BIO to cultures BIO significantly promoted establishment of goat mGSC colonies and maintained their undifferentiated state.

We present a fortuitous discovery of enhanced shape-selective recognition of anion guests that stems from a complexation-induced conformational change in porphyrin hosts upon anion binding. Porphyrin hosts reported here exist in a conformation that is not favorable to guest binding. Anions that bind strongly are those that can induce a conformational change in the host to allow guest binding. Furthermore, guests that mimic the shape of the newly formed pocket bind the strongest.

Abstract In this paper, we propose a multi-restart memetic algorithm framework for box-constrained global continuous optimisation. In this framework, an evolutionary algorithm (EA) and a local optimizer are employed as separated building blocks. The EA is used to explore the search space for very promising solutions (e.g., solutions in the attraction basin of the global optimum) through its exploration capability and previous EA search history, and local search is used to improve these promising solutions to local optima. An estimation of distribution algorithm (EDA) combined with a derivative free local optimizer, called NEWUOA (M. Powell, Developments of NEWUOA for minimization without derivatives. Journal of Numerical Analysis, 28:649-664, 2008, is developed based on this framework and empirically compared with several well-known EAs on a set of 40 commonly-used test functions. The main components of the specific algorithm include:(1) an adaptive multivariate probability model,(2) a multiple sampling strategy,(3) decoupling of the hybridisation strategy, and (4) a restart mechanism. The adaptive multivariate probability model and multiple sampling strategy are designed to enhance the exploration capability. The restart mechanism attempts to make the search escape from local optima, resorting to previous search history. Comparison results show that the algorithm is comparable with the best known EAs, including the winner of the 2005 IEEE Congress on Evolutionary Computation (CEC2005), and significantly better than the others in terms of both the solution quality and computational cost.

A novel iron-catalysed tandem cross-dehydrogenative coupling and benzoannulation process was developed for the synthesis of biologically and synthetically important polysubstituted naphthalene derivatives from simple 1,2-aryl-propenes and styrenes in moderate to good yields.