Impact pressures generated by spherical particle hypervelocity impact on Yorkshire Sandstone

Hypervelocity impact tests were carried out at 4.8 km/s using the Open University's All Axis Light Gas Gun (AALGG) in the Planetary and Space Sciences Research Institute (PSSRI)'s Hypervelocity Impact Laboratory. A first estimate of the peak loading pressures was made using preliminary hydrocode simulations, supported by calculations. Following a review of existing published quartz and sandstone data, our previously published plate impact data were combined with high pressure quartz data to produce a synthetic Hugoniot. This will form the basis of future hydrocode modelling, as a linear Us-Up relationship does not adequately represent the behaviour of sandstone over the pressure range of interest, as indicated by experimental data on Coconino sandstone. This work is a precursor to investigating the biological effects of shock on microorganisms in sandstone targets. This paper also contains the first presentation of results of ultra high speed imaging of hypervelocity impact at the Open University. © 2007 American Institute of Physics

Evaluation of mTOR-regulated mRNA translation.

mTOR, the mammalian target of rapamycin, regulates protein synthesis (mRNA translation) by affecting the phosphorylation or activity of several translation factors. Here, we describe methods for studying the impact of mTOR signalling on protein synthesis, using inhibitors of mTOR such as rapamycin (which impairs some of its functions) or mTOR kinase inhibitors (which probably block all functions).To assess effects of mTOR inhibition on general protein synthesis in cells, the incorporation of radiolabelled amino acids into protein is measured. This does not yield information on the effects of mTOR on the synthesis of specific proteins. To do this, two methods are described. In one, stable-isotope labelled amino acids are used, and their incorporation into new proteins is determined using mass spectrometric methods. The proportions of labelled vs. unlabeled versions of each peptide from a given protein provide quantitative information about the rate of that protein's synthesis under different conditions. Actively translated mRNAs are associated with ribosomes in polyribosomes (polysomes); thus, examining which mRNAs are found in polysomes under different conditions provides information on the translation of specific mRNAs under different conditions. A method for the separation of polysomes from non-polysomal mRNAs is describe

Promoting evidence-based decision making in a local health department, Pueblo City-County, Colorado

BACKGROUND: Evidence-based decision making (EBDM) is an effective strategy for addressing population health needs. Assessing and reducing barriers to using EBDM in local health departments may improve practice and provide insight into disseminating EBDM principles among public health practitioners. COMMUNITY CONTEXT: Administrative leaders at the Pueblo City–County Health Department, Pueblo, Colorado, used a systematic approach for implementing EBDM. Research partners engaged staff to understand factors that increase or deter its use. METHODS: A survey was distributed to staff members at baseline to identify gaps in administrative and individual practice of EBDM. In-depth interviews were also conducted with 11 randomly selected staff members. Results were shared with staff and administration, after which activities were implemented to improve application of EBDM. A follow up survey was administered 1 year after the initial assessment. OUTCOME: Survey data showed evidence of progress in engaging and educating staff members, and data showed improved attitudes toward EBDM (ie, several items showed significant improvement from baseline to follow-up). For example, staff members reported having the necessary skills to develop evidence-based interventions (73.9%), the ability to effectively communicate information on evidence-based strategies to policy makers (63.0%), access to current information on improving EBDM processes (65.2%), and a belief that evidence-based interventions are designed to be self-sustaining (43.5%). INTERPRETATION: Within a local health department in which leaders have made EBDM a priority, addressing the culture and climate of the department may build EBDM. Future research may provide insight into tailoring EBDM within and across local health departments

Biochemical effects of mutations in the gene encoding the alpha subunit of eukaryotic initiation factor (eIF) 2B associated with Vanishing White Matter disease

BACKGROUND: Leukoencephalopathy with Vanishing White Matter (VWM) is an autosomal recessive disorder caused by germline mutations in the genes EIF2B1-5, which encode the 5 subunits of the eukaryotic translation initiation factor eIF2B. To date, analysis of the biochemical effects of mutations in the EIF2B2-5 genes has been carried out, but no study has been performed on mutations in the EIF2B1 gene. This gene encodes eIF2Bα, the smallest subunit in eIF2B which has an important role in both the structure and regulation of the eIF2B complex. METHODS: eIF2B subunits were overexpressed in HEK293 cells and isolated from the resulting cell lysates by affinity chromatography. Formation of the eIF2B complex and binding of its substrate, eIF2, was assessed by western blot. Assays of the guanine nucleotide exchange (GEF) activity were also carried out. RESULTS: Of the 5 eIF2Bα mutations studied, we found 3 that showed loss or reduction of binding of eIF2Bα to the rest of the complex, one with increased GEF activity, and one where no effects on activity or complex formation were observed. CONCLUSIONS: This is the first study on eIF2Bα VWM mutations. We show that some mutations cause expected decreases in GEF activity or complex formation, similar to a majority of observed VWM mutations. However, we also observe some unexpected changes which hint at other effects of these mutations on as yet undescribed functions of eIF2B.Noel C. Wortham, and Christopher G. Prou

Polymer Nanocomposite Materials Based on Carbon Nanotubes

(Invited Book Chapter

Examining the role of wine brand love on brand loyalty: a multi-country comparison

This study develops and tests a model through a multi-country study that considers consumer wine knowledge and wine experience, wine brand trust and wine brand satisfaction as antecedents of wine brand love, and wine brand loyalty as a consequence of wine brand love. Data were collected in five wine-producing countries (Australia, Chile, France, Mexico and Portugal) with a final sample of 3462 completed surveys. Hypotheses were tested with structural equation modeling and the findings confirm the importance of brand love as both a mediator and direct influence on brand loyalty for wine consumers. Furthermore, brand satisfaction was positively and significantly related to brand love. In addition, wine experience, rather than wine knowledge, positively influenced brand trust and satisfaction. Finally, results also identify differences between countries thereby providing insights into how companies should focus their marketing strategies internationally.info:eu-repo/semantics/acceptedVersio

MNK1 and MNK2 mediate adverse effects of high-fat feeding in distinct ways

The MAP kinase-interacting kinases (MNK1 and MNK2) are non-essential enzymes which are activated by MAP kinases. They are implicated in controlling protein synthesis. Here we show that mice in which the expression of either MNK1 or MNK2 has been knocked out (KO) are protected against adverse effects of high-fat feeding, and in distinct ways. High-fat diet (HFD)-fed MNK2-KO show less weight gain than wild-type animals, and improved glucose tolerance, better insulin sensitivity and markedly diminished adipose tissue inflammation. This suggests MNK2 plays a role in adipogenesis and/or lipogenesis and in macrophage biology. MNK1-KO/HFD mice show better glucose tolerance and insulin sensitivity, but gain weight and show similar adipose inflammation to WT animals. These data suggest MNK1 participates in mediating HFD-induced insulin resistance. Our findings reveal distinct roles for the MNKs in a novel area of disease biology, metabolic dysfunction, and suggests they are potential new targets for managing metabolic disease

Ribosomal stress activates eEF2K-eEF2 pathway causing translation elongation inhibition and recruitment of Terminal Oligopyrimidine (TOP) mRNAs on polysomes

The synthesis of adequate amounts of ribosomes is an essential task for the cell. It is therefore not surprising that regulatory circuits exist to organize the synthesis of ribosomal components. It has been shown that defect in ribosome biogenesis (ribosomal stress) induces apoptosis or cell cycle arrest through activation of the tumor suppressor p53. This mechanism is thought to be implicated in the pathophysiology of a group of genetic diseases such as Diamond Blackfan Anemia which are called ribosomopathies. We have identified an additional response to ribosomal stress that includes the activation of eukaryotic translation elongation factor 2 kinase with a consequent inhibition of translation elongation. This leads to a translational reprogramming in the cell that involves the structurally defined group of messengers called terminal oligopyrimidine (TOP) mRNAs which encode ribosomal proteins and translation factors. In fact, while general protein synthesis is decreased by the impairment of elongation, TOP mRNAs are recruited on polysomes causing a relative increase in the synthesis of TOP mRNA-encoded proteins compared to other proteins. Therefore, in response to ribosomal stress, there is a change in the translation pattern of the cell which may help restore a sufficient level of ribosomes