Sensitivity-based scaling for correlating structural response from different analytical models

A sensitivity-based linearly varying scale factor is described used to reconcile results from refined models for analysis of the same structure. The improved accuracy of the linear scale factor compared to a constant scale factor as well as the commonly used tangent approximation is demonstrated. A wing box structure is used as an example, with displacements, stresses, and frequencies correlated. The linear scale factor could permit the use of a simplified model in an optimization procedure during preliminary design to approximate the response given by a refined model over a considerable range of design changes

A role for the histone deacetylase HDAC4 in the life-cycle of HIV-1-based vectors

HIV-1 integration is mediated by the HIV-1 integrase protein, which joins 3'-ends of viral DNA to host cell DNA. To complete the integration process, HIV-1 DNA has to be joined to host cell DNA also at the 5'-ends. This process is called post-integration repair (PIR). Integration and PIR involve a number of cellular co-factors. These proteins exhibit different degrees of involvement in integration and/or PIR. Some are required for efficient integration or PIR. On the other hand, some reduce the efficiency of integration. Finally, some are involved in integration site selection. We have studied the role of the histone deacetylase HDAC4 in these processes. HDAC4 was demonstrated to play a role in both cellular double-strand DNA break repair and transcriptional regulation. We observed that HDAC4 associates with viral DNA in an integrase-dependent manner. Moreover, infection with HIV-1-based vectors induces foci of the HDAC4 protein. The related histone deacetylases, HDAC2 and HDAC6, failed to associate with viral DNA after infection. These data suggest that HDAC4 accumulates at integration sites. Finally, overexpression studies with HDAC4 mutants suggest that HDAC4 may be required for efficient transduction by HIV-1-based vectors in cells that are deficient in other DNA repair proteins. We conclude that HDAC4 is likely involved in PIR

Gamma radiation increases endonuclease-dependent L1 retrotransposition in a cultured cell assay

Long Interspersed Elements (LINE-1s, L1s) are the most active mobile elements in the human genome and account for a significant fraction of its mass. The propagation of L1 in the human genome requires disruption and repair of DNA at the site of integration. As Barbara McClintock first hypothesized, genotoxic stress may contribute to the mobilization of transposable elements, and conversely, element mobility may contribute to genotoxic stress. We tested the ability of genotoxic agents to increase L1 retrotransposition in a cultured cell assay. We observed that cells exposed to gamma radiation exhibited increased levels of L1 retrotransposition. The L1 retrotransposition frequency was proportional to the number of phosphorylated H2AX foci, an indicator of genotoxic stress. To explore the role of the L1 endonuclease in this context, endonuclease-deficient tagged L1 constructs were produced and tested for their activity in irradiated cells. The activity of the endonuclease-deficient L1 was very low in irradiated cells, suggesting that most L1 insertions in irradiated cells still use the L1 endonuclease. Consistent with this interpretation, DNA sequences that flank L1 insertions in irradiated cells harbored target site duplications. These results suggest that increased L1 retrotransposition in irradiated cells is endonuclease dependent. The mobilization of L1 in irradiated cells potentially contributes to genomic instability and could be a driving force for secondary mutations in patients undergoing radiation therapy

Histone deacetylase 4 interacts with 53BP1 to mediate the DNA damage response

Anumber of proteins are recruited to nuclear foci upon exposure to double-strand DNA damage, including 53BP1 and Rad51, but the precise role of these DNA damage–induced foci remain unclear. Here we show in a variety of human cell lines that histone deacetylase (HDAC) 4 is recruited to foci with kinetics similar to, and colocalizes with, 53BP1 after exposure to agents causing double-stranded DNA breaks. HDAC4 foci gradually disappeared in repair-proficient cells but persisted in repair-deficient cell lines or cells irradiated with a lethal dose, suggesting that resolution of HDAC4 foci is linked to repair. Silencing of HDAC4 via RNA interference surprisingly also decreased levels of 53BP1 protein, abrogated the DNA damage–induced G2 delay, and radiosensitized HeLa cells. Our combined results suggest that HDAC4 is a critical component of the DNA damage response pathway that acts through 53BP1 and perhaps contributes in maintaining the G2 cell cycle checkpoint

Phenotypic and functional characterization of corneal endothelial cells during in vitro expansion.

The advent of cell culture-based methods for the establishment and expansion of human corneal endothelial cells (CEnC) has provided a source of transplantable corneal endothelium, with a significant potential to challenge the one donor-one recipient paradigm. However, concerns over cell identity remain, and a comprehensive characterization of the cultured CEnC across serial passages has not been performed. To this end, we compared two established CEnC culture methods by assessing the transcriptomic changes that occur during in vitro expansion. In confluent monolayers, low mitogenic culture conditions preserved corneal endothelial cell state identity better than culture in high mitogenic conditions. Expansion by continuous passaging induced replicative cell senescence. Transcriptomic analysis of the senescent phenotype identified a cell senescence signature distinct for CEnC. We identified activation of both classic and new cell signaling pathways that may be targeted to prevent senescence, a significant barrier to realizing the potential clinical utility of in vitro expansion

Association Between Parental History of Type 2 Diabetes and Glycemic Control in Urban African Americans

OBJECTIVE—The purpose of this study was to examine the association between parental history of type 2 diabetes and glycemic control among diabetic urban African Americans

The Los Alamos General Circulation Model hydrologic cycle

As the global population has increased, so have human influences on the global environment. ... How can we better understand and predict these natural and potential anthropogenic variations? One way is to develop a model that can accurately describe all the components of the hydrologic cycle, rather than just the end result variables such as precipitation and soil moisture. If we can predict and simulate variations in evaporation and moisture convergence, as well as precipitation, then we will have greater confidence in our ability to at least model precipitation variations. Therefore, we describe here just how well we can model relevant aspects of the global hydrologic cycle. In particular, we determine how well we can model the annual and seasonal mean global precipitation, evaporation, and atmospheric water vapor transport

Nucleation of PP-Branes and Fundamental Strings

We construct a solution to the low-energy string equations of motion in five dimensions that describes a circular loop of fundamental string exponentially expanding in a background electric $H$-field. Euclideanising this gives an instanton for the creation of a loop of fundamental string in a background $H$-field, and we calculate the rate of nucleation. Solutions describing magnetically charged strings and $p$-branes, where the gauge field comes from Kaluza-Klein reduction on a circle, are also constructed. It is known that a magnetic flux tube in four (reduced) spacetime dimensions is unstable to the pair creation of Kaluza-Klein monopoles. We show that in $(4+p)$ dimensions, magnetic $(p+1)$ ``fluxbranes" are unstable to the nucleation of a magnetically charged spherical $p$-brane. In ten dimensions the instanton describes the nucleation of a Ramond-Ramond magnetically charged six-brane in type IIA string theory. We also find static solutions describing spherical charged $p$-branes or fundamental strings held in unstable equilibrium in appropriate background fields. Instabilities of intersecting magnetic fluxbranes are also discussed.Comment: 28 pages, harvmac (b), reference added, typos correcte

Boron Isotopic Analysis of Representative Atmospheric Aerosols Derived From Long-Range Transported/Local Emission on an Islet Offshore NE Taiwan

To identify pollutant origins and their potential sources from either long-range transported (LRT) or local emissions, the Boron (B) concentrations and the B isotopic compositions (δ11B) in the water-soluble fraction of aerosols were determined. These aerosols were collected from an islet offshore in northeastern Taiwan, Peng Chia Yu (PCY), a non-residential islet, from January 1998 to March 2000. This islet may be influenced by various pollutants or chemical transport during monsoon periods, but suffers minimal human perturbation locally. The B in the specimens falls to 0.3–1.63 ng m−3 during the SW monsoon seasons when compared to 0.46–2.56 ng m−3 in the NE monsoon. However, the δ11B results show no clear variations in both monsoon seasons (10.7–24.3‰), regardless of differences in air mass origin. A two end-member mixing scenario is proposed to explain our observations using the obtained δ11B and 1/[B] results. The ocean endmember is characterized by high 1/[B] and high δ11B; while other endmember is from continental endmember or anthropogenic contributions that are characterized by of 1/[B] and lowδ11B (δ11B < 10‰). Based on these chemical and isotopic results, we found aerosol emissions in northern Taiwan are characterized as low B with nearly constant δ11B, when compared with long-range transported continental endmembers derived from nearby regions. This study provides preliminary B and δ11B levels in aerosols derived from LRT/local emissions and discusses potential monsoonal effects on aerosols offshore of NE Taiwan