1,990 research outputs found

    Rare earthquake response spectra for typical site conditions in Hong Kong

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    Hong Kong is located in a region of low-to-moderate seismicity; the potential consequences in the event of a nearby major earthquake should not be underrated. In the past two decades, researchers have conducted many studies on this issue and it is now clear that design procedures should not be directly borrowed from other codes of practice without modifications. This paper aims at presenting the rare earthquake response spectra for typical rock and soil sites in Hong Kong, which form the basis of a seismic design procedure. The uniform hazard spectrum (UHS) for rock sites was obtained from seismic hazard assessment using probabilistic methods. Records from 16 boreholes, representing a wide range of local site conditions, were collected from different locations in Hong Kong. A site-specific response spectrum was then constructed based on the results of site response analyses. Moreover, the 16 site-specific response spectra have been grouped into four types based on the (initial) site natural periods, which allows convenient evaluation of the loading characteristics that are expected at different types of sites. Finally, the rare earthquake response spectra proposed for Hong Kong are compared with those constructed based on the Chinese code (GB) and the Eurocode (EC8).postprin

    Entrepreneurial capital, social values and Islamic traditions: exploring the growth of women-owned enterprises in Pakistan

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    Main ArticleThis study seeks to explore the variables contributing to the growth of women-owned enterprises in the Islamic Republic of Pakistan. Based on a previously established multivariate model, it uses two econometric approaches: first classifying variables into predetermined blocks; and second, using the general to specific approach. Statistical analyses and in-depth interviews confirm that women entrepreneurs’ personal resources and social capital have a significant role in their business growth. Further, it reveals that the moral support of immediate family, independent mobility and being allowed to meet with men play a decisive role in the sales and employment growth of women-owned enterprises in an Islamic country such as Pakistan

    Prolonged Fasting Reduces IGF-1/PKA to Promote Hematopoietic-Stem-Cell-Based Regeneration and Reverse Immunosuppression

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    Immune system defects are at the center of aging and a range of diseases. Here, we show that prolonged fasting reduces circulating IGF-1 levels and PKA activity in various cell populations, leading to signal transduction changes in long-term hematopoietic stem cells (LT-HSCs) and niche cells that promote stress resistance, self-renewal, and lineage-balanced regeneration. Multiple cycles of fasting abated the immunosuppression and mortality caused by chemotherapy and reversed age-dependent myeloid-bias in mice, in agreement with preliminary data on the protection of lymphocytes from chemotoxicity in fasting patients. The proregenerative effects of fasting on stem cells were recapitulated by deficiencies in either IGF-1 or PKA and blunted by exogenous IGF-1. These findings link the reduced levels of IGF-1 caused by fasting to PKA signaling and establish their crucial role in regulating hematopoietic stem cell protection, self-renewal, and regeneration

    Directed differentiation of human pluripotent stem sells for the generation of high-order kidney organoids

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    Our understanding in the inherent properties of human pluripotent stem cells (hPSCs) have made possible the development of differentiation procedures to generate three-dimensional tissue-like cultures, so-called organoids. Here we detail a stepwise methodology to generate kidney organoids from hPSCs. This is achieved through direct differentiation of hPSCs in two-dimensional monolayer culture toward the posterior primitive streak fate, followed by induction of intermediate mesoderm-committed cells, which are further aggregated and cultured in three-dimensions to generate kidney organoids containing segmented nephron-like structures in a process that lasts 20 days. We also provide a concise description on how to assess renal commitment during the time course of kidney organoid generation. This includes the use of flow cytometry and immunocytochemistry analyses for the detection of specific renal differentiation markers

    Mechanical degradation of biomass wood pellets during long term stockpile storage

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    This paper quantifies and assesses the mechanical degradation of white wood and steam exploded wood pellets in indoor and outdoor stockpile storage over a twenty-one month period in the UK. The indoor stored steam exploded wood pellets on the surface of the pile only exhibited a 3% decrease in durability after twenty months in storage. The outdoor stored pellets demonstrated much higher levels of mechanical degradation. In the summer period with high relative humidity and temperature, the durability of pellets sampled from the surface of the pile dropped from 92 to 22% after three months in storage with a durability of 10% measured after nine months in storage. The degradation of the pellets from the middle of the pile was more gradual and less severe with a maximum durability drop of 34%. The impact on mechanical properties was significant for the indoor stored white wood pellets with pellets quickly degrading to dust. This study shows that while steam exploded pellets could be stored in covered storage, white wood pellets require a fully enclosed storage environment. Short term outdoor storage of steam exploded pellets could be considered if extended periods of low rainfall and relative humidity can be reliably predicted

    Enhanced detection of early hepatocellular carcinoma by serum SELDI-TOF proteomic signature combined with alpha-fetoprotein marker.

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    BACKGROUND: Biomarkers for accurate diagnosis of early hepatocellular carcinoma (HCC) are limited in number and clinical validation. We applied SELDI-TOF-MS ProteinChip technology to identify serum profile for distinguishing HCC and liver cirrhosis (LC) and to compare the accuracy of SELDI-TOF-MS profile and alpha-fetoprotein (AFP) level in HCC diagnosis. PATIENTS AND METHODS: Serum samples were obtained from 120 HCC and 120 LC patients for biomarker discovery and validation studies. ProteinChip technology was employed for generating SELDI-TOF proteomic features and analyzing serum proteins/peptides. RESULTS: A diagnostic model was established by CART algorithm, which is based on 5 proteomic peaks with m/z values at 3324, 3994, 4665, 4795, and 5152. In the training set, the CART algorithm could differentiate HCC from LC subjects with a sensitivity and specificity of 98% and 95%, respectively. The results were assessed in blind validation using separate cohorts of 60 HCC and 60 LC patients, with an accuracy of 83% for HCC and 92% for LC patients. The diagnostic odd ratio (DOR) indicated that SELDI-TOF proteomic signature could achieve better diagnostic performance than serum AFP level at a cutoff of 20 ng/mL (AFP(20)) (92.72 vs 9.11), particularly superior for early-stage HCC (87% vs 54%). Importantly, a combined use of both tests could enhance the detection of HCC (sensitivity, 95%; specificity, 98%; DOR, 931). CONCLUSION: Serum SELDI-TOF proteomic signature, alone or in combination with AFP marker, promises to be a good tool for early diagnosis and/screening of HCC in at-risk population with liver cirrhosis

    The prognostic role of intragenic copy number breakpoints and identification of novel fusion genes in paediatric high grade glioma

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    BACKGROUND: Paediatric high grade glioma (pHGG) is a distinct biological entity to histologically similar tumours arising in older adults, and has differing copy number profiles and driver genetic alterations. As functionally important intragenic copy number aberrations (iCNA) and fusion genes begin to be identified in adult HGG, the same has not yet been done in the childhood setting. We applied an iCNA algorithm to our previously published dataset of DNA copy number profiling in pHGG with a view to identify novel intragenic breakpoints. RESULTS: We report a series of 288 iCNA events in pHGG, with the presence of intragenic breakpoints itself a negative prognostic factor. We identified an increased number of iCNA in older children compared to infants, and increased iCNA in H3F3A K27M mutant tumours compared to G34R/V and wild-type. We observed numerous gene disruptions by iCNA due to both deletions and amplifications, targeting known HGG-associated genes such as RB1 and NF1, putative tumour suppressors such as FAF1 and KIDINS220, and novel candidates such as PTPRE and KCND2. We further identified two novel fusion genes in pHGG - CSGALNACT2:RET and the complex fusion DHX57:TMEM178:MAP4K3. The latter was sequence-validated and appears to be an activating event in pHGG. CONCLUSIONS: These data expand upon our understanding of the genomic events driving these tumours and represent novel targets for therapeutic intervention in these poor prognosis cancers of childhood.We are grateful for support from the Rosetrees Trust, the Brain Tumour Charity and Fundacao para a Ciencia e Tecnologia, Portugal (PhD Studentship SFRH/BD/33473/2008). DC, AM, LB and CJ acknowledge NHS funding to the Biomedical Research Centre
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