2,714 research outputs found
Dynamic strategic responses among advertisers: the case of meat products
The case of strategic advertising response is examined for branded and generic meat products (beef, pork, and poultry). A dynamic conceptual model is developed to identify the determinants of advertising expenditures. A time-series model is then used to examine the competitive behavior of branded and generic meat advertisers. The results identify two types of advertising strategies those based upon changes in revenues and those based upon changes in competitor advertising expenditures. Most groups employ a mix of revenue-based and advertising-based strategies. The results identify examples of both strategic substitutes and strategic complements. No long-run response to generic advertising by brand advertisers in the same commodity group is found.advertising strategy
Multiple-Access Bosonic Communications
The maximum rates for reliably transmitting classical information over
Bosonic multiple-access channels (MACs) are derived when the transmitters are
restricted to coherent-state encodings. Inner and outer bounds for the ultimate
capacity region of the Bosonic MAC are also presented. It is shown that the
sum-rate upper bound is achievable with a coherent-state encoding and that the
entire region is asymptotically achievable in the limit of large mean input
photon numbers.Comment: 11 pages, 5 figures, corrected two figures, accepted for publication
in Phys. Rev.
Quantum Monte Carlo for minimum energy structures
We present an efficient method to find minimum energy structures using energy
estimates from accurate quantum Monte Carlo calculations. This method involves
a stochastic process formed from the stochastic energy estimates from Monte
Carlo that can be averaged to find precise structural minima while using
inexpensive calculations with moderate statistical uncertainty. We demonstrate
the applicability of the algorithm by minimizing the energy of the H2O-OH-
complex and showing that the structural minima from quantum Monte Carlo
calculations affect the qualitative behavior of the potential energy surface
substantially.Comment: 7 pages, 4 figure
The Unique N- And C-Terminal Domains Of Metallothionein-3 Influence The Growth And Differentiation Of Breast Cancer Cells
Toxic insult from the heavy metal cadmium is known to induce the expression of metallothioneins (MT) which are cysteine-rich heavy metal binding proteins six to seven kilodaltons in size. Previous research demonstrates that over-expression of MT-3 occurs in the majority of breast cancers and is associated with poor patient outcome. Furthermore, MT-3 has been shown to inhibit the growth of breast cancer and prostate cancer cell lines. Studies have shown that the MT-3 protein contains 7 additional amino acids that are not present in any other member of the MT gene family, a 6 amino acid C-terminal sequence and a Thr in the N-terminal region. The unique N-terminal sequence is responsible for the growth inhibitory activity of MT-3 in the neuronal system, while the function of C-terminal region remains unknown. The unique N- and C-terminal domains of MT-3 may play alternative roles in the differentiation and growth of breast cancer cells.
One goal of this study was to characterize the function of the N- and C-terminal domains of MT-3 in the MCF7 breast cancer cell line. For this purpose six different constructs of MTs were prepared which were as follows: wild type (WT) MT-3, MT-3 N-terminal site directed mutagenesis (MT-3 P7T P9T), MT-3 C-terminal deletion (MT-3 E55_E60del), WT MT-1E, and MT-1E mutated to contain the N -terminal of MT-3 (MT-1E N4_C5insTCPCP), or the C-terminal (MT-1E G52_A53insEAAEAE), or both the N- and the C-terminal of MT-3 (MT-1E N4_C5insTCPCP and G52_A53insEAAEAE). Each of these constructs was transfected into MCF7 cells. Both the growth rate and the
transepithelial resistance (TER) of each cell line were measured. Growth rates were statistically significantly reduced in all cell lines except MCF7 parent, Blank Vector, and MT-1E. Vectorial active transport was increased in WT MT-3 and mutants containing the C-terminal of MT-3 as indicated by the formation of domes and increased TER. Observations of confluent cell cultures of mutant cell lines were also performed to determine the doming phenotype. Doming was observed in cell cultures possessing the C-terminal region of MT-3, and the WT MT-3 cell line. The data obtained suggests that the N-terminal region of MT-3 is involved in growth inhibitory activity even in the absence of the C-terminal domain. The C-terminal region is involved in vectorial active transport which is indicated by the formation of domes in cell culture. Depending on cell culture conditions the N-terminal region of MT-3 may attenuate the C-terminal domainâs ability to confer the doming phenotype.
Microarray analysis of the MCF7 mutants was also performed to determine alterations in gene expression. Overlapping hierarchal clustering demonstrates that the N- and C-terminal mutants have unique expression relationships. Genes that were differentially regulated on the microarray and were further validated included the GAGE family antigens. Several GAGE antigens were investigated to examine differential expression between the N- and C-terminal of MT-3. These included: GAGE12H, GAGE12G, GAGE4, GAGE5, GAGE6, GAGE2E-1, GAGE2E-2, GAGE2E-1E, and GAGE2C. A significant repression of GAGE2C, GAGE2E-1, GAGE2E-2, GAGE5, GAGE6, and GAGE12H antigen expression was seen in MCF7 mutants NT-1E, WT MT-3, and MT-3ÎCT. Up regulation of GAG2C, GAGE2E-2, GAGE5, and GAGE12H antigens occurred in MCF7 mutants MT-1E and CT-1E. The GAGE12G antigen demonstrated increased expression in only MCF7 mutant cell lines MT-1E, CT-1E, and MT-3ÎNT. The GAGE6 antigen was the only antigen to show repression in the presence of the N-terminal of MT-3 and up regulation in the presence of the C-terminal of MT-3 but not in the presence of MT-1E.
In conclusion, this study further characterizes the unique properties of the N- and the C-terminal domain of MT-3 and the potential role that it may play in the differentiation of certain breast cancers. Dendrogram clustering analysis suggests that the N-terminal and C-terminal domains of MT-3 differentially regulate gene expression in MCF7 cells. Increased doming activity and increased doubling times of mutant cell lines containing the C-terminal is suggestive of a differentiated phenotype of the cell line. Differential regulation of GAGE antigens and E-cadherin in the presence of MT-3 could be indicative of MT-3âs role in the epithelial to mesenchymal transition of cancer cells
Diagnostic Assessment of Autism Spectrum Disorder: A Cross-Disciplinary Analysis
To date, there are no known biological markers to diagnose Autism Spectrum Disorder (ASD). Thus, diagnosis generally relies on behavioural assessment and considerable clinical judgement. Currently, very little is known about the assessment methodology Canadian physicians and psychologists use, to diagnose ASD. The current study provides information regarding these practices. A total of 64 participants (23 physicians and 41 psychologists) completed an online survey. Overall, the participants reported a relatively homogenous set of assessment practices. Small differences were noted in the usage of some assessment tools and in the composition of their clinical team. Assessment tool usage differed depending on the estimated cognitive level of the client population a clinician worked with. Limitations and future directions for the research are discussed. It is hoped that these results will help promote further research into the clinical practice of diagnosticians working with children diagnosed with (or being assessed for) ASD
Spatial and temporal variations in indoor environmental conditions, human occupancy, and operational characteristics in a new hospital building.
The dynamics of indoor environmental conditions, human occupancy, and operational characteristics of buildings influence human comfort and indoor environmental quality, including the survival and progression of microbial communities. A suite of continuous, long-term environmental and operational parameters were measured in ten patient rooms and two nurse stations in a new hospital building in Chicago, IL to characterize the indoor environment in which microbial samples were taken for the Hospital Microbiome Project. Measurements included environmental conditions (indoor dry-bulb temperature, relative humidity, humidity ratio, and illuminance) in the patient rooms and nurse stations; differential pressure between the patient rooms and hallways; surrogate measures for human occupancy and activity in the patient rooms using both indoor air CO2 concentrations and infrared doorway beam-break counters; and outdoor air fractions in the heating, ventilating, and air-conditioning systems serving the sampled spaces. Measurements were made at 5-minute intervals over consecutive days for nearly one year, providing a total of âŒ8Ă106 data points. Indoor temperature, illuminance, and human occupancy/activity were all weakly correlated between rooms, while relative humidity, humidity ratio, and outdoor air fractions showed strong temporal (seasonal) patterns and strong spatial correlations between rooms. Differential pressure measurements confirmed that all patient rooms were operated at neutral pressure. The patient rooms averaged about 100 combined entrances and exits per day, which suggests they were relatively lightly occupied compared to higher traffic environments (e.g., retail buildings) and more similar to lower traffic office environments. There were also clear differences in several environmental parameters before and after the hospital was occupied with patients and staff. Characterizing and understanding factors that influence these building dynamics is vital for hospital environments, where they can impact patient health and the survival and spread of healthcare associated infections
Hexosamines Provoke Membrane Cholesterol Accrual, Filamentous Actin Loss, and GLUT4 Dysregulation in Adipocytes through Transcriptional Activation of Specificity Protein 1
poster abstractThe hexosamine biosynthesis pathway (HBP) serves as a sensor of excess nutrient bioavailability and has been implicated in the pathogenesis of type 2 diabetes. Previous study observed that hyperinsulinemic culturing conditions akin to those seen clinically activate the HBP provoking gains in plasma membrane (PM) cholesterol content in L6 myotubes and 3T3-L1 adipocytes. This, in turn, compromised the cortical filamentous actin (F-actin) structure necessary for the proper incorporation of the insulin sensitive glucose transporter GLUT4 into the membrane. The mechanism(s), however, by which HBP activation provokes PM cholesterol accrual, remains unclear. Here, the hypothesis that HBP engages a cholesterolgenic transcriptional response resulting in PM cholesterol accrual/toxicity was tested. In 3T3-L1 adipocytes, pathophysiologically relevant doses of hyperinsulinemia (0.25, 0.5, and 5 nM) resulted in a dose-dependent gain in PM cholesterol as well as mRNA and protein levels of HMG-CoA reductase (HMGR), the rate limiting enzyme in cholesterol synthesis. Immunoprecipitation experiments demonstrated that hyperinsulinemia induced elevations in O-linked N-acetylglucosamine post-translational modification of the cholesterolgenic transcription factor specificity protein 1 (Sp1). This modification was prevented in cells in which the HBP was inhibited. Chromatin immunoprecipitation demonstrated that hyperinsulinemia induced a ~4 fold increase in the affinity of Sp1 to the promoter region of HMGR, which was lost with HBP inhibition. Luciferase assays confirmed that this altered binding resulted in a ~50% increase in promoter activity of this cholesterolgenic gene. Hyperinsulinemia also augmented Sp1 binding to the promoter of the sterol response element binding protein gene, resulting in increased total and nuclear content of this factor. To further delineate the role of Sp1 in this process, a specific inhibitor, mithramycin (MTR), of Sp1 binding to DNA was employed. This inhibitor prevented against hyperinsulinemia-induced gains in HMGR and PM cholesterol as well as F-actin loss. Importantly, this treatment corrected the impaired insulin-stimulated GLUT4 translocation and glucose transport induced by hyperinsulinemia. These data suggest hyperinsulinemia-induced HBP activity provokes cholesterol synthesis and PM cholesterol accrual/F-actin loss that compromises GLUT4/glucose transport regulation by insulin
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