Chronicles of Oklahoma

Notes and Documents section for Volume 48, Number 1, Spring 1970. It includes a correction for the placement of two illustrations in the previous issue, an announcement for the distribution of the Annual Index, a report of changes in staff and activities within the history department at Oklahoma State University, a note on the opening of the Museum of the Great Lakes, and a list of recent accessions to the library

Vibrational Properties of Nanoscale Materials: From Nanoparticles to Nanocrystalline Materials

The vibrational density of states (VDOS) of nanoclusters and nanocrystalline materials are derived from molecular-dynamics simulations using empirical tight-binding potentials. The results show that the VDOS inside nanoclusters can be understood as that of the corresponding bulk system compressed by the capillary pressure. At the surface of the nanoparticles the VDOS exhibits a strong enhancement at low energies and shows structures similar to that found near flat crystalline surfaces. For the nanocrystalline materials an increased VDOS is found at high and low phonon energies, in agreement with experimental findings. The individual VDOS contributions from the grain centers, grain boundaries, and internal surfaces show that, in the nanocrystalline materials, the VDOS enhancements are mainly caused by the grain-boundary contributions and that surface atoms play only a minor role. Although capillary pressures are also present inside the grains of nanocrystalline materials, their effect on the VDOS is different than in the cluster case which is probably due to the inter-grain coupling of the modes via the grain-boundaries.Comment: 10 pages, 7 figures, accepted for publication in Phys. Rev.

Evaluation of the third- and fourth-generation GOCE Earth gravity field models with Australian terrestrial gravity data in spherical harmonics

In March 2013 the fourth generation of ESA’s (European Space Agency) global gravity field models, DIR4 (Bruinsma et al, 2010b) and TIM4 (Pail et al, 2010), generated from the GOCE (Gravity field and steady-state Ocean Circulation Explorer) gravity observation satellite were released. We evaluate the models using an independent ground truth data set of gravity anomalies over Australia. Combined with GRACE (Gravity Recovery and Climate Experiment) satellite gravity, a new gravity model is obtained that is used to perform comparisons with GOCE models in spherical harmonics. Over Australia, the new gravity model proves to have significantly higher accuracy in the degrees below 120 as compared to EGM2008 and seems to be at least comparable to the accuracy of this model between degree 150 and degree 260. Comparisons in terms of residual quasi-geoid heights, gravity disturbances, and radial gravity gradients evaluated on the ellipsoid and at approximate GOCE mean satellite altitude (h=250 km) show both fourth generation models to improve significantly w.r.t. their predecessors.Relatively, we find a root-mean-square improvement of 39 % for the DIR4 and 23 % for TIM4 over the respective third release models at a spatial scale of 100 km (degree 200). In terms of absolute errors TIM4 is found to perform slightly better in the bands from degree 120 up to degree 160 and DIR4 is found to perform slightly better than TIM4 from degree 170 up to degree 250. Our analyses cannot confirm the DIR4 formal error of 1 cm geoid height (0.35 mGal in terms of gravity) at degree 200. The formal errors of TIM4, with 3.2 cm geoid height (0.9 mGal in terms of gravity) at degree 200, seem to be realistic. Due to combination with GRACE and SLR data, the DIR models, at satellite altitude, clearly show lower RMS values compared to TIM models in the long wavelength part of the spectrum (below degree and order 120). Our study shows different spectral sensitivity of different functionals at ground level and at GOCE satellite altitude and establishes the link among these findings and the Meissl scheme (Rummel and van Gelderen in Manuscripta Geodaetica 20:379–385, 1995)

The quantitative calculation of SiC polytypes from measurements of X-ray diffraction peak intensities

An experimental determination on powder mixtures of SiC-3C and 6H polytypes using an X-ray goniometer system showed the possibility of quantitative determination of polytype fraction directly from peak intensities. In combination with calculated X-ray intensities of 15R and 4H polytype, the method yields a simple equation system for the relative quantities of SiC polytypes 15R, 6H, 4H and 3C in polycrystalline samples and powder mixtures.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44679/1/10853_2004_Article_BF00551044.pd

Genome-wide transcriptomic analysis of the response to nitrogen limitation in Streptomyces coelicolor A3(2)

<p>Abstract</p> <p>Background</p> <p>The present study represents a genome-wide transcriptomic analysis of the response of the model streptomycete <it>Streptomyces coelicolor </it>A3(2) M145 to fermentor culture in Modified Evans Media limited, respectively, for nitrogen, phosphate and carbon undertaken as part of the ActinoGEN consortium to provide a publicly available reference microarray dataset.</p> <p>Findings</p> <p>A microarray dataset using samples from two replicate cultures for each nutrient limitation was generated. In this report our analysis has focused on the genes which are significantly differentially expressed, as determined by Rank Products Analysis, between samples from matched time points correlated by growth phase for the three pairs of differently limited culture datasets. With a few exceptions, genes are only significantly differentially expressed between the N6/N7 time points and their corresponding time points in the C and P-limited cultures, with the vast majority of the differentially expressed genes being more highly expressed in the N-limited cultures. Our analysis of these genes indicated expression of several members of the GlnR regulon are induced upon nitrogen limitation, as assayed for by [NH₄⁺] measurements, and we are able to identify several additional genes not present in the GlnR regulon whose expression is induced in response to nitrogen limitation. We also note SCO3327 which encodes a small protein (32 amino acid residues) unusually rich in the basic amino acids lysine (31.25%) and arginine (25%) is significantly differentially expressed in the nitrogen limited cultures. Additionally, we investigate the expression of known members of the GlnR regulon and the relationship between gene organization and expression for the SCO2486-SCO2487 and SCO5583-SCO5585 operons.</p> <p>Conclusions</p> <p>We provide a list of genes whose expression is differentially expressed in low nitrogen culture conditions, including a putative nitrogen storage protein encoded by SCO3327. Our list includes several genes whose expression patterns are similar to up-regulated members of the GlnR regulon and are induced in response to nitrogen limitation. These genes represent likely targets for future studies into the nitrogen starvation response in <it>Streptomyces coelicolor</it>.</p

Reversing Melanoma Cross-Resistance to BRAF and MEK Inhibitors by Co-Targeting the AKT/mTOR Pathway

The sustained clinical activity of the BRAF inhibitor vemurafenib (PLX4032/RG7204) in patients with BRAF(V600) mutant melanoma is limited primarily by the development of acquired resistance leading to tumor progression. Clinical trials are in progress using MEK inhibitors following disease progression in patients receiving BRAF inhibitors. However, the PI3K/AKT pathway can also induce resistance to the inhibitors of MAPK pathway.The sensitivity to vemurafenib or the MEK inhibitor AZD6244 was tested in sensitive and resistant human melanoma cell lines exploring differences in activation-associated phosphorylation levels of major signaling molecules, leading to the testing of co-inhibition of the AKT/mTOR pathway genetically and pharmacologically. There was a high degree of cross-resistance to vemurafenib and AZD6244, except in two vemurafenib-resistant cell lines that acquired a secondary mutation in NRAS. In other cell lines, acquired resistance to both drugs was associated with persistence or increase in activity of AKT pathway. siRNA-mediated gene silencing and combination therapy with an AKT inhibitor or rapamycin partially or completely reversed the resistance.Primary and acquired resistance to vemurafenib in these in vitro models results in frequent cross resistance to MEK inhibitors, except when the resistance is the result of a secondary NRAS mutation. Resistance to BRAF or MEK inhibitors is associated with the induction or persistence of activity within the AKT pathway in the presence of these drugs. This resistance can be potentially reversed by the combination of a RAF or MEK inhibitor with an AKT or mTOR inhibitor. These combinations should be available for clinical testing in patients progressing on BRAF inhibitors

Disruption of Retinoic Acid Receptor Alpha Reveals the Growth Promoter Face of Retinoic Acid

Retinoic acid (RA), the bioactive derivative of Vitamin A, by epigenetically controlling transcription through the RA-receptors (RARs), exerts a potent antiproliferative effect on human cells. However, a number of studies show that RA can also promote cell survival and growth. In the course of one of our studies we observed that disruption of RA-receptor alpha, RARalpha, abrogates the RA-mediated growth-inhibitory effects and unmasks the growth-promoting face of RA (Ren et al., Mol. Cell. Biol., 2005, 25:10591). The objective of this study was to investigate whether RA can differentially govern cell growth, in the presence and absence of RARalpha, through differential regulation of the "rheostat" comprising ceramide (CER), the sphingolipid with growth-inhibitory activity, and sphingosine-1-phosphate (S1P), the sphingolipid with prosurvival activity.We found that functional inhibition of endogenous RARalpha in breast cancer cells by using either RARalpha specific antagonists or a dominant negative RARalpha mutant hampers on one hand the RA-induced upregulation of neutral sphingomyelinase (nSMase)-mediated CER synthesis, and on the other hand the RA-induced downregulation of sphingosine kinase 1, SK1, pivotal for S1P synthesis. In association with RA inability to regulate the sphingolipid rheostat, cells not only survive, but also grow more in response to RA both in vitro and in vivo. By combining genetic, pharmacological and biochemical approaches, we mechanistically demonstrated that RA-induced growth is, at least in part, due to non-RAR-mediated activation of the SK1-S1P signaling.In the presence of functional RARalpha, RA inhibits cell growth by concertedly, and inversely, modulating the CER and S1P synthetic pathways. In the absence of a functional RARalpha, RA-in a non-RAR-mediated fashion-promotes cell growth by activating the prosurvival S1P signaling. These two distinct, yet integrated processes apparently concur to the growth-promoter effects of RA

DNA microarray data integration by ortholog gene analysis reveals potential molecular mechanisms of estrogen-dependent growth of human uterine fibroids

BACKGROUND: Uterine fibroids or leiomyoma are a common benign smooth muscle tumor. The tumor growth is well known to be estrogen-dependent. However, the molecular mechanisms of its estrogen-dependency is not well understood. METHODS: Differentially expressed genes in human uterine fibroids were either retrieved from published papers or from our own statistical analysis of downloaded array data. Probes for the same genes on different Affymetrix chips were mapped based on probe comparison information provided by Affymetrix. Genes identified by two or three array studies were submitted for ortholog analysis. Human and rat ortholog genes were identified by using ortholog gene databases, HomoloGene and TOGA and were confirmed by synteny analysis with MultiContigView tool in the Ensembl genome browser. RESULTS: By integrated analysis of three recently published DNA microarray studies with human tissue, thirty-eight genes were found to be differentially expressed in the same direction in fibroid compared to adjacent uterine myometrium by at least two research groups. Among these genes, twelve with rat orthologs were identified as estrogen-regulated from our array study investigating uterine expression in ovariectomized rats treated with estrogen. Functional and pathway analyses of the twelve genes suggested multiple molecular mechanisms for estrogen-dependent cell survival and tumor growth. Firstly, estrogen increased expression of the anti-apoptotic PCP4 gene and suppressed the expression of growth inhibitory receptors PTGER3 and TGFBR2. Secondly, estrogen may antagonize PPARγ signaling, thought to inhibit fibroid growth and survival, at two points in the PPAR pathway: 1) through increased ANXA1 gene expression which can inhibit phospholipase A2 activity and in turn decrease arachidonic acid synthesis, and 2) by decreasing L-PGDS expression which would reduce synthesis of PGJ2, an endogenous ligand for PPARγ. Lastly, estrogen affects retinoic acid (RA) synthesis and mobilization by regulating expression of CRABP2 and ALDH1A1. RA has been shown to play a significant role in the development of uterine fibroids in an animal model. CONCLUSION: Integrated analysis of multiple array datasets revealed twelve human and rat ortholog genes that were differentially expressed in human uterine fibroids and transcriptionally responsive to estrogen in the rat uterus. Functional and pathway analysis of these genes suggest multiple potential molecular mechanisms for the poorly understood estrogen-dependent growth of uterine fibroids. Fully understanding the exact molecular interactions among these gene products requires further study to validate their roles in uterine fibroids. This work provides new avenues of study which could influence the future direction of therapeutic intervention for the disease