The influence of joints and composite floor slabs on effective tying of steel structures in preventing progressive collapse

The event of the terrorist attack at 11th September 2001 in the USA has attracted increasing attention of researchers and engineers on progressive collapse of structures. It has gradually become a general practice for engineers to consider progressive collapse resistance in their design. In this paper, progressive collapse of steel frames with composite floor slabs is simulated by the finite element method. The numerical results are compared with test results. The influence of the joints and the concrete slabs on the effective tying of steel beams is investigated through parametric studies. From the analysis, methods of preventing progressive collapse that can be considered in design and when retrofitting existing structures are proposed. The results show that retrofitting a structure with pre-stressed steel cables and an increase of crack resistance in the concrete near joints can effectively improve effective tying of a structure, which results in an enhanced structural capacity in preventing progressive collapse

Analysis on GNSS receiver with the principles of signal and information

In the paper, principles of signal and information were introduced to the design of GNSS receiver. Analyze Antenna and radio frequency (RF) front-end with the perspective of transmission link, Understand the baseband processing though signal modulate and demodulate, design the navigation calculation utilized the information pick-up and disposal, and research the receiver system by the inherent connection between signal and information. New ways and means would be developed though these researches. © (2013) Trans Tech Publications, Switzerland

Impacts of climate change on hydropower generation in China

Analyzing the impact of climate change on China's hydropower system can make great contribution to understanding the feedback mechanism of the climate change on energy system. In this work, an econometric model for regional hydropower generation is constructed to explore the impact of climate factors on hydropower generation in different regions of China by using the monthly panel data of 28 provinces in China. Further, we also make a prediction for the changes of hydropower generation in China caused by the changes of climatic factors under the three climate change scenarios (RCP2.6, RCP4.5 and RCP8.5) proposed in the Intergovernmental Panel on Climate Change's (IPCC) fifth assessment report. The results show that: (1) At the national level, the influences of climatic factors on hydropower generation are significant, the elasticity coefficients of rainfall, heating degree day (HDD), cooling degree day (CDD) and sunshine duration are 0.081, -0.016, 0.089 and -0.043 respectively. (2) The impacts of climatic factors on the hydropower generation in the northern and southern regions of China are different. The effect of rainfall on the hydropower generation is significant in the southern regions, but not in the northern region. The CDD has a significant effect on both the northern and southern regions, and the latter is greater (0.136%). The impact of HDD on the northern area is significant, while its influence on the southern area is not significant. The influence of sunshine duration is not significant in any region in China. (3) Compared with the year of 2011, the total changes of hydropower output caused by climate factors by 2100 under the RCP8.5, RCP4.5 and RCP2.6 scenarios are 153.29 billion kWh, 67.49 billion kWh and 22.10 billion kWh, respectively. The results imply that the hydropower is sensitive and vulnerable to climate fluctuation, leading to many uncertainties for its development in the future. Finally, some policy implications are proposed for the planning of hydropower in China

Identification and optimization of small molecule antagonists of vasoactive intestinal peptide receptor-1 (VIPR1)

Identification, synthesis and structure-activity relationship of small-molecule VIPR1 antagonists encompassing two chemical series are described

Surface-enhanced Raman spectroscopy study of 4-ATP on gold nanoparticles for basal cell carcinoma fingerprint detection

The surface-enhanced Raman signals of 4-aminothiophenol (4-ATP) attached to the surface of colloidal gold nanoparticles with size distribution of 2 to 5 nm were used as a labeling agent to detect basal cell carcinoma (BCC) of the skin. The enhanced Raman band at 1075 cm-1 corresponding to the C-S stretching vibration in 4-ATP was observed during attachment to the surface of the gold nanoparticles. The frequency and intensity of this band did not change when the colloids were conjugated with BerEP4 antibody, which specifically binds to BCC. We show the feasibility of imaging BCC by surface-enhanced Raman spectroscopy, scanning the 1075 cm-1 band to detect the distribution of 4ATP-coated gold nanoparticles attached to skin tissue ex vivo

Critical research gaps and translational priorities for the successful prevention and treatment of breast cancer

INTRODUCTION Breast cancer remains a significant scientific, clinical and societal challenge. This gap analysis has reviewed and critically assessed enduring issues and new challenges emerging from recent research, and proposes strategies for translating solutions into practice. METHODS More than 100 internationally recognised specialist breast cancer scientists, clinicians and healthcare professionals collaborated to address nine thematic areas: genetics, epigenetics and epidemiology; molecular pathology and cell biology; hormonal influences and endocrine therapy; imaging, detection and screening; current/novel therapies and biomarkers; drug resistance; metastasis, angiogenesis, circulating tumour cells, cancer 'stem' cells; risk and prevention; living with and managing breast cancer and its treatment. The groups developed summary papers through an iterative process which, following further appraisal from experts and patients, were melded into this summary account. RESULTS The 10 major gaps identified were: (1) understanding the functions and contextual interactions of genetic and epigenetic changes in normal breast development and during malignant transformation; (2) how to implement sustainable lifestyle changes (diet, exercise and weight) and chemopreventive strategies; (3) the need for tailored screening approaches including clinically actionable tests; (4) enhancing knowledge of molecular drivers behind breast cancer subtypes, progression and metastasis; (5) understanding the molecular mechanisms of tumour heterogeneity, dormancy, de novo or acquired resistance and how to target key nodes in these dynamic processes; (6) developing validated markers for chemosensitivity and radiosensitivity; (7) understanding the optimal duration, sequencing and rational combinations of treatment for improved personalised therapy; (8) validating multimodality imaging biomarkers for minimally invasive diagnosis and monitoring of responses in primary and metastatic disease; (9) developing interventions and support to improve the survivorship experience; (10) a continuing need for clinical material for translational research derived from normal breast, blood, primary, relapsed, metastatic and drug-resistant cancers with expert bioinformatics support to maximise its utility. The proposed infrastructural enablers include enhanced resources to support clinically relevant in vitro and in vivo tumour models; improved access to appropriate, fully annotated clinical samples; extended biomarker discovery, validation and standardisation; and facilitated cross-discipline working. CONCLUSIONS With resources to conduct further high-quality targeted research focusing on the gaps identified, increased knowledge translating into improved clinical care should be achievable within five years

TBC1D3, a Hominoid-Specific Gene, Delays IRS-1 Degradation and Promotes Insulin Signaling by Modulating p70 S6 Kinase Activity

Insulin/IGF-1 signaling plays a pivotal role in the regulation of cellular homeostasis through its control of glucose metabolism as well as due to its effects on cell proliferation. Aberrant regulation of insulin signaling has been repeatedly implicated in uncontrolled cell growth and malignant transformations. TBC1D3 is a hominoid specific gene previously identified as an oncogene in breast and prostate cancers. Our efforts to identify the molecular mechanisms of TBC1D3-induced oncogenesis revealed the role of TBC1D3 in insulin/IGF-1 signaling pathway. We document here that TBC1D3 intensifies insulin/IGF-1-induced signal transduction through intricate, yet elegant fine-tuning of signaling mechanisms. We show that TBC1D3 expression substantially delayed ubiquitination and degradation of insulin receptor substrate-1 (IRS-1). This effect is achieved through suppression of serine phosphorylation at S636/639, S307 and S312 of IRS-1, which are key phosphorylation sites required for IRS-1 degradation. Furthermore, we report that the effect of TBC1D3 on IRS-1:S636/639 phosphorylation is mediated through TBC1D3-induced activation of protein phosphatase 2A (PP2A), followed by suppression of T389 phosphorylation on p70 S6 kinase (S6K). TBC1D3 specifically interacts with PP2A regulatory subunit B56γ, indicating that TBC1D3 and PP2A B56γ operate jointly to promote S6K:T389 dephosphorylation. These findings suggest that TBC1D3 plays an unanticipated and potentially unique role in the fine-tuning of insulin/IGF-1 signaling, while providing novel insights into the regulation of tumorigenesis by a hominoid-specific protein