Damage Patterns/Response of Deep Stiff Clay in Oakland

The 1985 Mexico City earthquake and the 1989 Loma Prieta earthquake provided well-documented evidence of the effect of local ground conditions on site response and damage patterns. Deep soft clay deposits, in particular, were often cited as the culprit of amplified ground motions. However, during the 1989 Loma Prieta earthquake, ground accelerations in the downtown Oakland area were amplified by a factor of two to four and a significant number of structures were heavily damaged, despite the fact that much of the area is underlain by deposits of deep stiff clay. A preliminary review of damage patterns in the Oakland area and preliminary site response analyses were performed to investigate the influence of deep stiff clay deposits on the observed ground motions

Doxorubicin in Combination with a Small TGFβ Inhibitor: A Potential Novel Therapy for Metastatic Breast Cancer in Mouse Models

Recent studies suggested that induction of epithelial-mesenchymal transition (EMT) might confer both metastatic and self-renewal properties to breast tumor cells resulting in drug resistance and tumor recurrence. TGFbeta is a potent inducer of EMT and has been shown to promote tumor progression in various breast cancer cell and animal models.We report that chemotherapeutic drug doxorubicin activates TGFbeta signaling in human and murine breast cancer cells. Doxorubicin induced EMT, promoted invasion and enhanced generation of cells with stem cell phenotype in murine 4T1 breast cancer cells in vitro, which were significantly inhibited by a TGFbeta type I receptor kinase inhibitor (TbetaRI-KI). We investigated the potential synergistic anti-tumor activity of TbetaR1-KI in combination with doxorubicin in animal models of metastatic breast cancer. Combination of Doxorubicin and TbetaRI-KI enhanced the efficacy of doxorubicin in reducing tumor growth and lung metastasis in the 4T1 orthotopic xenograft model in comparison to single treatments. Doxorubicin treatment alone enhanced metastasis to lung in the human breast cancer MDA-MB-231 orthotopic xenograft model and metastasis to bone in the 4T1 orthotopic xenograft model, which was significantly blocked when TbetaR1-KI was administered in combination with doxorubicin.These observations suggest that the adverse activation of TGFbeta pathway by chemotherapeutics in the cancer cells together with elevated TGFbeta levels in tumor microenvironment may lead to EMT and generation of cancer stem cells resulting in the resistance to the chemotherapy. Our results indicate that the combination treatment of doxorubicin with a TGFbeta inhibitor has the potential to reduce the dose and consequently the toxic side-effects of doxorubicin, and improve its efficacy in the inhibition of breast cancer growth and metastasis

The major human and mouse granzymes are structurally and functionally divergent

Approximately 2% of mammalian genes encode proteases. Comparative genomics reveals that those involved in immunity and reproduction show the most interspecies diversity and evidence of positive selection during evolution. This is particularly true of granzymes, the cytotoxic proteases of natural killer cells and CD8+ T cells. There are 5 granzyme genes in humans and 10 in mice, and it is suggested that granzymes evolve to meet species-specific immune challenge through gene duplication and more subtle alterations to substrate specificity. We show that mouse and human granzyme B have distinct structural and functional characteristics. Specifically, mouse granzyme B is 30 times less cytotoxic than human granzyme B and does not require Bid for killing but regains cytotoxicity on engineering of its active site cleft. We also show that mouse granzyme A is considerably more cytotoxic than human granzyme A. These results demonstrate that even “orthologous” granzymes have species-specific functions, having evolved in distinct environments that pose different challenges

A systematic review and meta-analysis of the prevalence, trends, and geographical distribution of HIV among Chinese female sex workers (2000-2011): implications for preventing sexually transmitted HIV.

OBJECTIVE: The aim of this meta-analysis was to investigate temporal and geographical trends in the HIV epidemic among female sex workers (FSWs) recruited from various venues in China. METHODS: Chinese and English peer-reviewed articles published between January 2000 and February 2013 were systematically searched. Standard meta-analysis methods were used to calculate the pooled HIV prevalence, in accordance with the PRISMA guidelines. RESULTS: The national HIV prevalence among FSWs declined from 0.74% (95% confidence interval (CI) 0.37-1.49%) in 2000-2002 to 0.40% (95% CI 0.31-0.53%) in 2009-2011. All Chinese regions demonstrated significant declines in HIV prevalence, apart from the East and South Central regions, in which the epidemics stabilized at low/moderate levels. Despite a significant decline from 1.92% (95% CI 0.86-4.24%) to 0.87% (95% CI 0.65-1.18%) during 2000-2011, Southwest China still bore the greatest HIV disease burden. Nationwide, FSWs recruited from detention centres had the highest HIV prevalence (0.92%, 95% CI 0.46-1.88%), followed by voluntary counselling and testing sites (0.80%, 95% CI 0.46-1.67%) and entertainment venues (0.61%, 95% CI 0.47-0.79%). The prevalences among FSWs in high-, middle-, and low-tier entertainment venues were 0.59% (95% CI 0.32-1.45%), 0.92% (95% CI 0.50-1.77%), and 1.10% (95% CI 0.71-2.16%), respectively. High- and middle-tier FSWs had a significantly lower risk of HIV infection than lower-tier FSWs (high/low: odds ratio (OR) 0.48, 95% CI 0.40-0.59; middle/low: OR 0.49, 95% CI 0.37-0.66). CONCLUSIONS: The HIV epidemic has shown a gradual declining or stabilizing trend among Chinese FSWs. Intervention efforts should be diverted to high-risk subgroups of FSWs, such as drug-using and low-tier FSWs

Oxidized phospholipids are proinflammatory and proatherogenic in hypercholesterolaemic mice.

Oxidized phospholipids (OxPL) are ubiquitous, are formed in many inflammatory tissues, including atherosclerotic lesions, and frequently mediate proinflammatory changes 1 . Because OxPL are mostly the products of non-enzymatic lipid peroxidation, mechanisms to specifically neutralize them are unavailable and their roles in vivo are largely unknown. We previously cloned the IgM natural antibody E06, which binds to the phosphocholine headgroup of OxPL, and blocks the uptake of oxidized low-density lipoprotein (OxLDL) by macrophages and inhibits the proinflammatory properties of OxPL2-4. Here, to determine the role of OxPL in vivo in the context of atherogenesis, we generated transgenic mice in the Ldlr-/- background that expressed a single-chain variable fragment of E06 (E06-scFv) using the Apoe promoter. E06-scFv was secreted into the plasma from the liver and macrophages, and achieved sufficient plasma levels to inhibit in vivo macrophage uptake of OxLDL and to prevent OxPL-induced inflammatory signalling. Compared to Ldlr-/- mice, Ldlr -/- E06-scFv mice had 57-28% less atherosclerosis after 4, 7 and even 12 months of 1% high-cholesterol diet. Echocardiographic and histologic evaluation of the aortic valves demonstrated that E06-scFv ameliorated the development of aortic valve gradients and decreased aortic valve calcification. Both cholesterol accumulation and in vivo uptake of OxLDL were decreased in peritoneal macrophages, and both peritoneal and aortic macrophages had a decreased inflammatory phenotype. Serum amyloid A was decreased by 32%, indicating decreased systemic inflammation, and hepatic steatosis and inflammation were also decreased. Finally, the E06-scFv prolonged life as measured over 15 months. Because the E06-scFv lacks the functional effects of an intact antibody other than the ability to bind OxPL and inhibit OxLDL uptake in macrophages, these data support a major proatherogenic role of OxLDL and demonstrate that OxPL are proinflammatory and proatherogenic, which E06 counteracts in vivo. These studies suggest that therapies inactivating OxPL may be beneficial for reducing generalized inflammation, including the progression of atherosclerosis, aortic stenosis and hepatic steatosis

Glutathione-triggered disassembly of isothermally responsive polymer nanoparticles obtained by nanoprecipitation of hydrophilic polymers

The encapsulation and selective delivery of therapeutic compounds within polymeric nanoparticles offers hope for the treatment of a variety of diseases. Traditional approaches to trigger selective cargo release typically rely on polymer degradation which is not always sensitive to the biological location of a material. In this report, we prepare nanoparticles from thermoresponsive polymers with a ‘solubility release catch’ at the chain-end. This release catch is exclusively activated in the presence of intracellular glutathione, triggering an ‘isothermal’ response and promoting a change in polymer solubility. This solubility switch leads to specific and rapid nanoparticle disassembly, release of encapsulated cargo and produces completely soluble polymeric side-products

Decision-Directed Channel Estimation Implementation for Spectral Efficiency Improvement in Mobile MIMO-OFDM

Channel estimation algorithms and their implementations for mobile receivers are considered in this paper. The 3GPP long term evolution (LTE) based pilot structure is used as a benchmark in a multiple-input multiple-output (MIMO) orthogonal frequency division multiplexing (OFDM) receiver. The decision directed (DD) space alternating generalized expectation-maximization (SAGE) algorithm is used to improve the performance from that of the pilot symbol based least-squares (LS) channel estimator. The performance is improved with high user velocities, where the pilot symbol density is not sufficient. Minimum mean square error (MMSE) filtering is also used in estimating the channel in between pilot symbols. The pilot overhead can be reduced to a third of the LTE pilot overhead with DD channel estimation, obtaining a ten percent increase in data throughput. Complexity reduction and latency issues are considered in the architecture design. The pilot based LS, MMSE and the SAGE channel estimators are implemented with a high level synthesis tool, synthesized with the UMC 0.18 μm CMOS technology and the performance-complexity trade-offs are studied. The MMSE estimator improves the performance from the simple LS estimator with LTE pilot structure and has low power consumption. The SAGE estimator has high power consumption but can be used with reduced pilot density to increase the data rate.National Science FoundationTekesElektrobitRenesas Mobile EuropeAcademy of FinlandNokia Siemens NetworksXilin