2,506 research outputs found

    Compilation and Review Manual, Volume 2

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    https://egrove.olemiss.edu/aicpa_guides/1846/thumbnail.jp

    Compilation and Review Manual, Volume 1

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    https://egrove.olemiss.edu/aicpa_guides/1845/thumbnail.jp

    Comparative Analysis of Immune Checkpoint Molecules and Their Potential Role in the Transmissible Tasmanian Devil Facial Tumor Disease

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    Immune checkpoint molecules function as a system of checks and balances that enhance or inhibit immune responses to infectious agents, foreign tissues, and cancerous cells. Immunotherapies that target immune checkpoint molecules, particularly the inhibitory molecules programmed cell death 1 and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), have revolutionized human oncology in recent years, yet little is known about these key immune signaling molecules in species other than primates and rodents. The Tasmanian devil facial tumor disease is caused by transmissible cancers that have resulted in a massive decline in the wild Tasmanian devil population. We have recently demonstrated that the inhibitory checkpoint molecule PD-L1 is upregulated on Tasmanian devil (Sarcophilus harrisii) facial tumor cells in response to the interferon-gamma cytokine. As this could play a role in immune evasion by tumor cells, we performed a thorough comparative analysis of checkpoint molecule protein sequences among Tasmanian devils and eight other species. We report that many of the key signaling motifs and ligand-binding sites in the checkpoint molecules are highly conserved across the estimated 162 million years of evolution since the last common ancestor of placental and non-placental mammals. Specifically, we discovered that the CTLA-4 (MYPPPY) ligand-binding motif and the CTLA-4 (GVYVKM) inhibitory domain are completely conserved across all nine species used in our comparative analysis, suggesting that the function of CTLA-4 is likely conserved in these species. We also found that cysteine residues for intra- and intermolecular disulfide bonds were also highly conserved. For instance, all 20 cysteine residues involved in disulfide bonds in the human 4-1BB molecule were also present in devil 4-1BB. Although many key sequences were conserved, we have also identified immunoreceptor tyrosine-based inhibitory motifs (ITIMs) and immunoreceptor tyrosine-based switch motifs (ITSMs) in genes and protein domains that have not been previously reported in any species. This checkpoint molecule analysis and review of salient features for each of the molecules presented here can serve as road map for the development of a Tasmanian devil facial tumor disease immunotherapy. Finally, the strategies can be used as a guide for veterinarians, ecologists, and other researchers willing to venture into the nascent field of wild immunology

    Singlet Oxygen Generation on Porous Superhydrophobic Surfaces: Effect of Gas Flow and Sensitizer Wetting on Trapping Efficiency

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    We describe physical-organic studies of singlet oxygen generation and transport into an aqueous solution supported on superhydrophobic surfaces on which silicon–phthalocyanine (Pc) particles are immobilized. Singlet oxygen (1O2) was trapped by a water-soluble anthracene compound and monitored in situ using a UV–vis spectrometer. When oxygen flows through the porous superhydrophobic surface, singlet oxygen generated in the plastron (i.e., the gas layer beneath the liquid) is transported into the solution within gas bubbles, thereby increasing the liquid–gas surface area over which singlet oxygen can be trapped. Higher photooxidation rates were achieved in flowing oxygen, as compared to when the gas in the plastron was static. Superhydrophobic surfaces were also synthesized so that the Pc particles were located in contact with, or isolated from, the aqueous solution to evaluate the relative effectiveness of singlet oxygen generated in solution and the gas phase, respectively; singlet oxygen generated on particles wetted by the solution was trapped more efficiently than singlet oxygen generated in the plastron, even in the presence of flowing oxygen gas. A mechanism is proposed that explains how Pc particle wetting, plastron gas composition and flow rate as well as gas saturation of the aqueous solution affect singlet oxygen trapping efficiency. These stable superhydrophobic surfaces, which can physically isolate the photosensitizer particles from the solution may be of practical importance for delivering singlet oxygen for water purification and medical devices

    The Prevalence of Physical Activity and Sedentary Behaviours Relative to Obesity among Adolescents from Al-Ahsa, Saudi Arabia: Rural versus Urban Variations

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    Purpose. The aims of this study were to explore the lifestyle of young people living in Al-Ahsa Governorate; to investigate differences due to gender, age, school type, and geographical location. Methods. 1270 volunteered youth (15–19 years) completed a self-report questionnaire that contained 47 items relating to patterns of physical activity (PA), sedentary activity, and eating habits. The questionnaire allows the calculation of total energy expenditure in metabolic equivalent (MET-min) values per week. Results. Significant differences in the PA levels of youth were evident with regard to gender, geographical areas, and type of school. Also, normal weight males reported the highest levels of PA compared to overweight and obese. Conclusions. Youth living in rural desert were less physically active than those living in urban or rural farm environments. Youth of “normal” weight were more active than obese. Males were more active than females and PA levels appeared to decline with age

    Class solutions for SABR-VMAT for high-risk prostate cancer with and without elective nodal irradiation

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    BACKGROUND: The purpose of this study is to find the optimal planning settings for prostate SABR-VMAT for high-risk prostate cancer patients irradiated to prostate only (PO) or prostate and pelvic lymph nodes (PPLN). METHODS: For 10 patients, plans using 6MV flattened, flattening-filter-free (FFF) 6MV (6 F) and FFF 10MV (10 F) photon beams with full and partial arc arrangements were generated and compared. The prescribed dose was 40Gy to the prostate with 25Gy to the PLN in 5 fractions. Plans were then evaluated for PTV coverage, dose fall-off, and OAR doses. The number of monitor units and the treatment delivery times were also compared. Statistical differences were evaluated using a paired sample Wilcoxon signed rank test with a significance level of 0.05%. RESULTS: A total of 150 plans were generated for this study. Acceptable PO plans were obtained using single arcs, while two arcs were necessary for PPLN. All plans were highly conformal (CI ≥1.3 and CN ≥0.90) with no significant differences in the PTV dose coverage. 6MV plans required significantly longer treatment time and had higher dose spillage compared to FFF plans. Superior plans were obtained using 10 F 300° partial arcs for PO with the lowest rectal dose, dose spillage and the shortest treatment times. For PPLN, 6 F and 10 F plans were equivalent. CONCLUSIONS: SABR-VMAT with FFF photon beams offers a clear benefit with respect to shorter treatment delivery times and reduced dose spillage. Class solutions using a single 10 F 300° arc for PO and two 10 F or 6 F partial 300° arcs for PPLN are proposed. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13014-016-0730-7) contains supplementary material, which is available to authorized users

    Superhydrophobic surfaces as a source of airborne singlet oxygen through free space for photodynamic therapy

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    A superhydrophobic (SH) sandwich system has been developed to enable "contact-free" airborne singlet oxygen (1O2) delivery to a water droplet. The contact-free feature means that the sensitizer is physically separated from the droplet, which presents opportunities for photodynamic therapy (PDT). Trapping of airborne 1O2 in a H2O droplet residing on a lower SH surface was monitored with 9,10-anthracene dipropionate dianion by varying distances to an upper 1O2-generating surface. Short distances of 20 μm efficiently delivered airborne 1O2 to the droplet in single-digit picomolar steady-state concentrations. Delivery decreases linearly with distance, but 50% of the 1O2 steady-state concentration is trapped at a distance of 300 μm from the generating surface. The 1270 nm luminescence intensity was measured within the SH sandwich system, confirming the presence of airborne 1O2. Physical quenching of 1O2 to ground-state 3O2 by the water droplet itself and both physical and chemical quenching of 1O2 by the water droplet containing the trap 9,10-anthracene dipropionate dianion are observed. Unlike a majority of work in the field of PDT with dissolved sensitizers, where 1O2 diffuses short (hundreds of nanometers) distances, we show the delivery of airborne 1O2 via a superhydrophobic surface is effective through air in tenths of millimeters distances to oxidize an organic compound in water. Our results provide not only potential relevance to PDT but also surface bacterial inactivation processes.Fil: Aebisher, David. University Of Rzeszow; PoloniaFil: Bartusik-Aebisher, Dorota. University Of Rzeszow; PoloniaFil: Belh, Sarah J.. City University of New York; Estados UnidosFil: Ghosh, Goutam. City University of New York; Estados UnidosFil: Durantini, Andres Matías. Universidad Nacional de Río Cuarto. Instituto para el Desarrollo Agroindustrial y de la Salud. - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto para el Desarrollo Agroindustrial y de la Salud; ArgentinaFil: Liu, Yang. City University of New York; Estados UnidosFil: Xu, QianFeng. City University of New York; Estados UnidosFil: Lyons, Alan M.. City University of New York; Estados UnidosFil: Greer, Alexander. City University of New York; Estados Unido
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