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The SULT1A1 R213H polymorphism is suggested to be implicated in the development and progression of breast cancer. However, the published findings are inconsistent. We therefore performed a meta-analysis of 8,454 breast cancer cases and 11,800 controls from 14 published case–control studies. We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association of the R213H polymorphism with breast cancer risk. Overall, our results suggested that there is no significant relationship between SULT1A1 R213H polymorphism and the risk of breast cancer. However, further ethnic population analysis revealed a significantly increased risk of breast cancer for HH allele carriers among Asians (for HH vs. RR: OR = 2.27, 95% CI = 1.11–4.63, P heterogeneity = 0.63; for the recessive model: OR = 2.03, 95% CI = 1.00–4.41, P heterogeneity = 0.62). Taken together, this meta-analysis suggests that the SULT1A1 R213H may be a low-penetrant risk factor for developing breast cancer in Asian population.

Polymorphisms of serotonin transporter (5-HTT) gene were hypothesized to be associated with ventricular septal defects (VSD) related ultrasonographic pulmonary arterial hypertension (PAH) susceptibility. To test this hypothesis, we performed a case-case study in Chinese population and genotyped two polymorphisms (5-HTTLPR and 5-HTTVNTR). The LL homozygote of 5-HTTLPR and 10/10 homozygote of 5-HTTVNTR were both associated with a significantly increased risk of VSD-related ultrasonographic PAH. Haplotype analysis showed haplotype L-10 were also associated with a significant increased risk of ultrasonic PAH. These findings suggest that 5-HTT polymorphisms may play a role in the etiology of VSD-related possible PAH.

Main-Memory Database (MMDB) System is more superior in less response times and higher transaction throughputs than traditional Disk- Resident Database (DRDB) System. But the high performance of MMDB depends on the single server's main memory capacity, which is restricted by hardware technologies and operating system. In order to resolve the contradiction between requirements of high performance and limited memory resource, we propose a scalable Main-Memory database system ScaMMDB which distributes data and operations to several nodes and makes good use of every node's resource. In this paper we'll present the architecture of ScaMMDB and discuss a data distribution strategy based on statistics and clustering. We evaluate our system and data distribution strategy by comparing with others. The results show that our strategy performs effectively and can improve the performance of ScaMMDB.

Main memory database(MMDB) has much higher performance than disk resident database(DRDB), but the architecture of hardware limits the scalability of memory capacity. In OLAP applications, comparing with data volume, main memory capacity is not big enough and it is hard to extend. In this paper, ScaMMDB prototype is proposed towards the scalability of MMDB. A multi-node structure is established to enable system to adjust total main memory capacity dynamically when new nodes enter the system or some nodes leave the system. ScaMMDB is based on open source MonetDB which is a typical column storage model MMDB, column data transmission module, column data distribution module and query execution plan re-writing module are developed directly in MonetDB. Any node in ScaMMDB can response user's requirements and SQL statements are transformed automatically into extended column operating commands including local commands and remote call commands. Operation upon certain column is pushed into the node where column is stored, current node acts as temporarily mediator to call remote commands and assembles the results of each column operations. ScaMMDB is a test bed for scalability of MMDB, it can extend to MMDB cluster, MMDB replication server, even peer-to-peer OLAP server for further applications.

RecQ helicases play a central role in maintaining genome stability and may interact with some important cancer-related proteins such as BRCA1. Mutations of the human RecQ helicase genes WRN and BLM lead to rare autosomal recessive disorders, Werner and Bloom syndromes, which are associated with premature aging and cancer predisposition, including breast cancer. In this case–control study of 1,004 breast cancer cases and 1,008 controls, we tested the hypothesis that non-conservative amino acid exchanges in WRN (leu1074Phe), BLM (Met298Thr) and BRCA1 (Pro871Leu) are independently or jointly associated with the risk of breast cancer in Chinese women. We found that the variant genotype of WRN Leu1074Phe was associated with a 1.36-fold significantly increased risk of breast cancer (OR = 1.36, 95% CI = 1.06–1.74). Moreover, a significant gene–environment interaction was evident between WRN leu1074Phe and age at menarche (P int = 0.02). Subjects carrying Phe/Phe genotype and with earlier age at menarche had 3.58-fold increased risk of breast cancer (OR = 3.58, 95% CI = 2.54–5.05). However, we did not find the significant main effect of polymorphisms in BLM and BRCA1 and also no locus–locus interactions were identified between WRN, BLM and BRCA1. These findings indicate that WRN leu1074Phe variant may contribute to the susceptibility of breast cancer in Chinese women.

Telomerase reactivation, which prevents telomere shortening and maintains cell viability, is crucial for the continued growth or progression of cancer cells. A minisatellite tandem repeat, MNS16A, located in the downstream of the human telomerase reverse transcriptase (hTERT) gene was recently identified and reported to have an effect on hTERT expression and telomerase activity. The aim of this study was to test the hypothesis that the MNS16A variant is associated with risk of breast cancer development and metastasis. We genotyped MNS16A variant in hTERT in a case-control study of 1029 histologically confirmed breast cancer patients and 1107 cancer-free controls in Chinese women. The variant genotypes (302/271, 302/243 and 243/243) of MNS16A were associated with a significantly increased risk of breast cancer [adjusted odds ratio (OR) = 1.50, 95% confidence interval (CI) = 1.15-1.96], compared with the wild-type 302/302 genotype. In stratified analyses, we found that the 302/271 genotype was associated with a significantly increased risk of axillary lymph nodes metastasis (adjusted OR = 2.13, 95% CI = 1.05-4.33) compared with wild-type 302/302 genotype. These findings indicate that the MNS16A variant in the hTERT gene may contribute to the risk of breast cancer development and metastasis in Chinese women.

In classic view, inhibitory heterotrimeric G protein alpha subunits 1, 2, and 3 (Gi1α, Gi2α and Gi3α) couple to Giα protein-coupled receptors (GiPCR) and then transduce signals from GiPCRs to downstream pathways in hormone and chemo-attractant signaling. Recent genetic evidence demonstrates that Giα proteins are crucial to embryo development and growth as well as tumorigenesis. However, the molecular mechanism underlying the implication of Giα proteins in this physiological and pathological process is largely unknown. Here we report that Giα proteins differentially regulate receptor tyrosine kinases (RTKs)-mediated activation of growth factor signaling. Gi1α and Gi3α double deficient (Gi1/3 DKO) mouse embryonic fibroblasts (MEFs), in which Gi2α expression is also lower than that in wild type cells, exhibited a clear defect in ERK1/2 activation by EGF, HB-EGF, insulin and IGF-I, but not aFGF, bFGF or high dose of serum (FBS). Further, Gi1/3 DKO MEFs were largely defective in Akt-mTORC1 activation by aFGF, bFGF, EGF, HB-EGF, serum, but not IGF-1 and insulin. The defect in Akt or ERK1/2 activation in Giα deficient MEFs was rescued upon reintroduction of Gi1α and Gi3α proteins. Interestingly, Giα deficiency impaired activation of Akt-mTROC1 and ERK1/2 by PDGF at a low, but not a high dose. Using a RNA interference strategy, we showed that knockdown of Giα proteins in either wt MEFs or triple negative breast cancer cells (MDA-MB231-D3H2-LN) led to a defect in Akt-mTROC1 and ERK1/2 activation, which is similar to that in Giα deficient cells in response to EGF, bFGF or IGF-1. Additional experimental analysis revealed that Giα proteins formed a complex with RTKs, Gab1, FRS2 and Shp2 in breast cancer cells in response to EGF, bFGF, or IGF-1. Gi1/3 DKO MEFs showed a defect in EGF- and IGF-1-induced interaction of Gab1 with SHP2, which is required for ERK1/2 activation by EGF and IGF-1, and a defect in bFGF-induced interaction of Grb2 with Gab1, which is required for Akt-mTORC1 activation by aFGF and bFGF. Finally, knockdown of Giα proteins impaired in vitro growth and invasion of breast cancer cells in response to bFGF, EGF, and IGF-1. Thus, Giα proteins are a differential mediator of RTK signaling in normal and breast cancer cells. Citation Format: Zhanwei Wang, Rica Dela-Cruz, meisheng Jiang, Wen-Ming Chu. Giα proteins are a differential mediator of activation of RTK signaling in normal and breast cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 529. doi:10.1158/1538-7445.AM2013-529

The activation of the extracellular-signal-regulated protein kinase (ERK) pathway and the PI3K/Akt/mTORC pathway by growth factors is mediated by the receptor tyrosine kinases (RTKs), and plays a crucial role in physiological and pathological processes including cell proliferation, growth, survival, migration, tumorigenesis and metastasis. We previously reported that the activation of the PI3K/Akt/mTORC1 in mouse embryonic fibroblasts (MEFs) by epidermal growth factor (EGF) and its family growth factors is mediated by the heterotrimeric G protein alpha inhibitory (Giα). Herein we demonstrated that Giα proteins are able to differentially regulate RTKs-mediated activation of the ERK and the Akt/mTORC1 pathways. Loss of Giα proteins in MEFs impaired activation of the ERK pathway by EGF, insulin-like growth factor (IGF) and Insulin, but not basic fibroblast growth factor (bFGF). Intriguingly, while activation of the Akt/mTORC1 pathway by EGF and bFGF was severely defective in Giα protein deficient cells, this activation was only slightly reduced in response to insulin and IGF. Also, Giα proteins were able to alter activation of the Akt/mTORC1 and the ERK pathways by serum and platelet-derived growth factor (PDGF) in a dose dependent manner. To further understand that how Giα proteins differentially regulate RTK-mediated activation of the Akt/mTORC1 and ERK pathways, we performed an immuno-precipitation study. Our results showed that growth factors were able to induce the association of Giα proteins with growth factor receptors and their downstream adaptor proteins. Loss of Giα proteins in MEFs impaired the association of growth factor receptors with their adaptor proteins indicating that Giα proteins act downstream of RTKs but upstream of the adaptor proteins. Finally, we examined a role of Giα proteins in cancer biology. Similar to results obtained from Giα deficient MEFs, knockdown of Giα proteins in several human cancer cell lines diminished activation of the Akt/mTORC1 and the ERK pathways by growth factors. As a result, Giα protein deficiency inhibited cancer cell growth and migration. Given the fact that growth factors and their receptor pathways play pivotal roles in tumorigenesis and metastasis of cancer, our findings may promote further understanding the molecular mechanism underline RTK signaling regulation in cancer biology and may have implications for cancer therapy. Supported by Department of Defense, Leukemia and Lymphoma Society and NIH. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2157. doi:1538-7445.AM2012-2157

Recent advances in soft robotics in academia have led to the adoption of soft grippers in industrial settings. Due to their soft bending actuators, these grippers can handle delicate objects with great care. However, due to their flexibility, the actuators are prone to out-of-plane deformations upon asymmetric loading. These undesired deformations lead to reduced grasp performance and may cause instability or failure of the grip. While the state-of-the-art contributions describe complex designs to limit those deformations, this work focuses on a complementary path investigating the material distribution. In this paper, a novel bending actuator is developed with improved out-of-plane deformation resistance by optimizing the material distribution in multi-material designs composed of two polymers with different mechanical properties. This is made possible by the strong interfacial strength of Diels-Alder chemical bonds in the used polymers, which have a self-healing capability. A Solid Isotropic Material with Penalization (SIMP) topology optimization is performed to increase the out-of-plane resistance. The actuator is simulated using FEA COMSOL in which the (hyper) elastic materials are simulated by Mooney-Rivlin models, fitted on experimental uniaxial tensile test data. This multi-material actuator and a reference single material actuator were manufactured and modeled. Via experimental characterization and validation in FEA simulations, it is shown that the actuator performance, characterized by the in-plane performance and out-plane resistance, can be increased by an optimized multi-material composition, without changing the geometrical shape of the actuator.

Background: Infections from microorganisms and parasites have been connected with either increased or decreased cancer risk. The objective of this study was to investigate whether infection by Echinococcus granulosus is associated with cancer risk. Methods: We assembled a pilot retrospective cohort of patients who were diagnosed as being infected by E. granulosus in Cyprus between 1930 and 2011. Age/gender-matched non-infected family members and neighbors were selected as references. Medical history was ascertained from each study subject through in-person interview. Cox proportional hazards regression analysis was performed to assess the association of being infected by E. granulosus with cancer risk. Results: Individuals with prior infection by E. granulosus (n=249) were more likely to have cancer compared to those without infection (n=753), 11.65% vs. 8.37% (p=0.0492). Survival analysis also showed that subjects with prior infection had a higher risk for developing cancer. The hazards ratio (HR) was 1.595, [95% confidence interval (CI) between 1.008 and 2.525]. The risk ratio did not change significantly (HR=1.536; 95% CI: 0.965–2.445) after adjusting for gender, year of birth, smoking status, alcohol consumption, and family history of cancer. Conclusions: Our study suggests that infection by E. granulosus may increase cancer risk. If this observation can be confirmed independently, further investigation of the mechanisms underlying the association is warranted.