895 research outputs found

    The Blackstone Group: A Case Study

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    The Blackstone Group, Inc., located in Beaumont, Texas, is a full-service advertising agency providing design, media, and marketing support for clients in southeast Texas and the Lake Charles, Louisiana, area. The agency was founded April 15, 1978, with its first offices above owners Lawrence and Samantha’s garage. They began with three accounts. Prior to beginning their agency, Lawrence worked for two other agencies, serving five years as Art Director of the first agency, and four years as Creative Director for the second agency. Samantha was employed as a bookkeeper in a third agency. Lawrence began as a freelance designer, doing project work. Shortly thereafter, Samantha joined him in the business. They moved out of the garage, and established an upscale business address located quite near their major clients. Once they became an agency, they β€œpitched” every opportunity. As a result, they captured a wide variety of accounts, requiring that they become knowledgeable in every aspect of the business. Whatever it took – media buys, copywriting, radio scripts, design, television sport, photography – they did it, and learned as they went. Currently, employing five people plus the principals, the agency is the market leader in the Beaumont area with an estimated 25% market share in those service markets in which they compete. They are recognized as the quality leader in their market, and have garnered an impressive collection of local, regional and national awards for design in both print and other media. Gross billings in 1998 were 3.9million.Capitalbillings,themeasureusedintheindustrytoreportagencysize,approximated3.9 million. Capital billings, the measure used in the industry to report agency size, approximated 4.7 million. (Contact author for a copy of the complete report.)Entrepreneurship

    Ovalization of Tubes Under Bending and Compression

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    An empirical equation has been developed that gives the approximate amount of ovalization for tubes under bending loads. Tests were made on tubes in the d/t range from 6 to 14, the latter d/t ratio being in the normal landing gear range. Within the range of the series of tests conducted, the increase in ovalization due to a compression load in combination with a bending load was very small. The bending load, being the principal factor in producing the ovalization, is a rather complex function of the bending moment, d/t ratio, cantilever length, and distance between opposite bearing faces. (author

    Constitutive Ion Fluxes and Substrate Binding Domains of Human Glutamate Transporters

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    Application of L-glutamate activates ionic currents in voltage-clamped Xenopus oocytes expressing cloned human excitatory amino acid transporters (EAATs). However, even in the absence of L-glutamate, the membrane conductance of oocytes expressing EAAT1 was significantly increased relative to oocytes expressing EAAT2 or control oocytes. Whereas transport mediated by EAAT2 is blocked by the non-transported competitive glutamate analog kainate (K = 14 ΞΌM), EAAT1 is relatively insensitive (K \u3e 3 mM). Substitution of a block of 76 residues from EAAT2 into EAAT1, in which 18 residues varied from EAAT1, conferred high affinity kainate binding to EAAT1, and application of kainate to oocytes expressing the chimeric transporter blocked a pre-existing monovalent cation conductance that displayed a permeability sequence K \u3e Na \u3e Li choline. The results identify a structural domain of glutamate transporters that influences kainate binding and demonstrate the presence of a constitutive ion-selective pore in the transporter

    Using pressure pulse seismology to examine basal criticality and the influence of sticky spots on glacial flow

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    Here we report results of water pressure pulse studies conducted at StorglaciΓ€ren (Sweden) and West Washmawapta Glacier (British Columbia, Canada). Comparison of pressure pulse records with meteorological conditions at StorglaciΓ€ren indicates that several periods of increased basal slip activity observed during a 10 day interval of summer 2008 were due to precipitation loading of the glacier surface, rather than to infiltration of surface water to the glacier bed; this indicates that the glacier bed was close to the failure strength for much of this interval. Pressure pulse magnitudes for the two glaciers were well-fit by power law distributions similar to those earlier observed at Trapridge Glacier (and similar in form to the Gutenberg-Richter relationship commonly used in seismology), suggesting that the mechanical processes that give rise to these distributions are robust features of soft-bedded glaciers. In contrast, interevent time distributions for both glaciers diverge from those observed at Trapridge Glacier for short recurrence intervals, suggesting that the factors that govern the rate at which these processes occur differ between glaciers. An examination of pressure pulse characteristics at West Washmawapta Glacier indicates that the establishment of a basal drainage system in summer 2008 resulted in increased stability and reduced sensitivity to meltwater input, suggesting that common assumptions about the relationship between meltwater production and ice flow are oversimplified. These results demonstrate that water pressure pulse observations can provide valuable insight into the dynamics of soft-bedded glaciers

    Elevated autoantibody content in rheumatoid arthritis synovia with lymphoid aggregates and the effect of rituximab

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    IntroductionThe purpose of this study was to quantitatively evaluate the contribution of synovial lymphoid aggregates to autoantibody (rheumatoid factor [RF] and anti-cyclic citrullinated peptide [anti-CCP]) and total immunoglobulin (IgG and IgM) production in rheumatoid arthritis (RA) patients and the effect thereon of the B-cell-depleting antibody, rituximab, in the ARISE (Assessment of Rituximab's Immunomodulatory Synovial Effects) trial.MethodsAutoantibodies as well as total IgM and IgG were quantified by enzyme-linked immunosorbent assay in extracts of synovial tissues and matched serum from patients with RA or osteoarthritis (OA). Synovial biopsies and serum were obtained at baseline and 8 weeks following rituximab therapy in 14 RA patients. A synovial/serum index (SSI) was calculated as the ratio of synovial to serum antibody/albumin, with values above 1 representing synovial enrichment. Lymphoid aggregates were evaluated histologically.ResultsAnti-CCP IgG, but not RF-IgM, was significantly enriched in RA synovia compared with serum. Total IgM and IgG were also enriched in RA, but not in OA. SSI correlated significantly with mRNA content for both IgM and IgG, demonstrating that it reflected synovial immunoglobulin production. RA synovia with lymphocyte aggregates contained significantly elevated RF-IgM and anti-CCP IgG compared with tissues with diffuse lymphoid infiltration. Rituximab treatment did not affect synovial autoantibody or total immunoglobulin SSI overall. However, in aggregate-containing tissues, rituximab significantly reduced total IgM and IgG SSI as well as IgM and IgG1 mRNA. Surprisingly, RF-IgM and anti-CCP IgG SSIs were unchanged by rituximab in aggregate-containing synovia.ConclusionsCombined with earlier observations that synovial lymphoid aggregates are unaltered by rituximab treatment, these data suggest that lymphoid aggregates may provide a protective niche for autoantibody-producing cells

    Planning and delivery of intensity modulated bolus electron conformal therapy

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    PURPOSE: Bolus electron conformal therapy (BECT) is a clinically useful, well-documented, and available technology. The addition of intensity modulation (IM) to BECT reduces volumes of high dose and dose spread in the planning target volume (PTV). This paper demonstrates new techniques for a process that should be suitable for planning and delivering IM-BECT using passive radiotherapy intensity modulation for electrons (PRIME) devices. METHODS: The IM-BECT planning and delivery process is an addition to the BECT process that includes intensity modulator design, fabrication, and quality assurance. The intensity modulator (PRIME device) is a hexagonal matrix of small island blocks (tungsten pins of varying diameter) placed inside the patient beam-defining collimator (cutout). Its design process determines a desirable intensity-modulated electron beam during the planning process, then determines the island block configuration to deliver that intensity distribution (segmentation). The intensity modulator is fabricated and quality assurance performed at the factory (.decimal, LLC, Sanford, FL). Clinical quality assurance consists of measuring a fluence distribution in a plane perpendicular to the beam in a water or water-equivalent phantom. This IM-BECT process is described and demonstrated for two sites, postmastectomy chest wall and temple. Dose plans, intensity distributions, fabricated intensity modulators, and quality assurance results are presented. RESULTS: IM-BECT plans showed improved D CONCLUSION: These results demonstrated the feasibility of translating IM-BECT to the clinic using the techniques presented for treatment planning, intensity modulator design and fabrication, and quality assurance processes

    Oxygen Glucose Deprivation in Rat Hippocampal Slice Cultures Results in Alterations in Carnitine Homeostasis and Mitochondrial Dysfunction

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    Mitochondrial dysfunction characterized by depolarization of mitochondrial membranes and the initiation of mitochondrial-mediated apoptosis are pathological responses to hypoxia-ischemia (HI) in the neonatal brain. Carnitine metabolism directly supports mitochondrial metabolism by shuttling long chain fatty acids across the inner mitochondrial membrane for beta-oxidation. Our previous studies have shown that HI disrupts carnitine homeostasis in neonatal rats and that L-carnitine can be neuroprotective. Thus, this study was undertaken to elucidate the molecular mechanisms by which HI alters carnitine metabolism and to begin to elucidate the mechanism underlying the neuroprotective effect of L-carnitine (LCAR) supplementation. Utilizing neonatal rat hippocampal slice cultures we found that oxygen glucose deprivation (OGD) decreased the levels of free carnitines (FC) and increased the acylcarnitine (AC): FC ratio. These changes in carnitine homeostasis correlated with decreases in the protein levels of carnitine palmitoyl transferase (CPT) 1 and 2. LCAR supplementation prevented the decrease in CPT1 and CPT2, enhanced both FC and the AC: FC ratio and increased slice culture metabolic viability, the mitochondrial membrane potential prior to OGD and prevented the subsequent loss of neurons during later stages of reperfusion through a reduction in apoptotic cell death. Finally, we found that LCAR supplementation preserved the structural integrity and synaptic transmission within the hippocampus after OGD. Thus, we conclude that LCAR supplementation preserves the key enzymes responsible for maintaining carnitine homeostasis and preserves both cell viability and synaptic transmission after OGD

    Breast cancer in lesbians and bisexual women: Systematic review of incidence, prevalence and risk studies

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    This article is made available through the Brunel Open Access Publishing Fund. Β© 2013 Meads and Moore; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background: The UK Parliamentary Enquiry and USA Institute of Medicine state that lesbians may be at a higher risk of breast cancer but there is insufficient information. Lesbians and bisexual (LB) women have behavioural risk-factors at higher rates compared to heterosexuals such as increased alcohol intake and higher stress levels. Conversely, breast cancer rates are higher in more affluent women yet income levels in LB women are relatively low. This systematic review investigated all evidence on whether there is, or likely to be, higher rates of breast cancer in LB women. Methods: Cochrane library (CDSR, CENTRAL, HTA, DARE, NHSEED), MEDLINE, EMBASE, PsychINFO, CAB abstracts, Web of Science (SCI, SSCI), SIGLE and Social Care Online databases were searched to October 2013. Unpublished research and specific lesbian, gay and bisexual websites were checked, as were citation lists of relevant papers. Included were studies in LB populations reporting breast cancer incidence or prevalence rates, risk model results or risk-factor estimates. Inclusions, data-extraction and quality assessment were by two reviewers with disagreements resolved by discussion. Results: Searches found 198 references. No incidence rates were found. Nine studies gave prevalence estimates - two showed higher, four showed no differences, one showed mixed results depending on definitions, one had no comparison group and one gave no sample size. All studies were small with poor methodological and/or reporting quality. One incidence modelling study suggested a higher rate. Four risk modelling studies were found, one Rosner-Colditz and three Gail models. Three suggested higher and one lower rate in LB compared to heterosexual women. Six risk-factor estimates suggested higher risk and one no difference between LB and heterosexual women. Conclusions: The only realistic way to establish rates in LB women would be to collect sexual orientation within routine statistics, including cancer registry data, or from large cohort studies
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