3,125 research outputs found

    Sex Abuse in the American Catholic Church and the Attempt at Redemption

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    The paper analyzes the apologia of Catholic leaders as they responded to accusations that surfaced in 2002 regarding priestly sex abuse in the United States. A study of the apologetic techniques used is offered, noting particularly bolstering, transcendence, and differentiation. Though it was Catholic leaders themselves who used the differentiation approach in their apologia, in their reaction to that rhetoric the audience members may have been influenced by the media and/or the leaders’ peers. Thus, rhetorical efforts by those two sources also are studied. The investigation concentrates primarily on the four-month period beginning January 9 when coverage was most intense, with some attention devoted to the remaining months of 2002

    Non-Contact Measurement of Thermal Diffusivity in Ion-Implanted Nuclear Materials

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    Knowledge of mechanical and physical property evolution due to irradiation damage is essential for the development of future fission and fusion reactors. Ion-irradiation provides an excellent proxy for studying irradiation damage, allowing high damage doses without sample activation. Limited ion-penetration-depth means that only few-micron-thick damaged layers are produced. Substantial effort has been devoted to probing the mechanical properties of these thin implanted layers. Yet, whilst key to reactor design, their thermal transport properties remain largely unexplored due to a lack of suitable measurement techniques. Here we demonstrate non-contact thermal diffusivity measurements in ion-implanted tungsten for nuclear fusion armour. Alloying with transmutation elements and the interaction of retained gas with implantation-induced defects both lead to dramatic reductions in thermal diffusivity. These changes are well captured by our modelling approaches. Our observations have important implications for the design of future fusion power plants.Comment: 15 pages, 3 figure

    A Chemical Biology Approach to Developing STAT Inhibitors: Molecular Strategies for Accelerating Clinical Translation

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    STAT transcription factors transduce signals from the cell surface to the nucleus, where they regulate the expression of genes that control proliferation, survival, self-renewal, and other critical cellular functions. Under normal physiological conditions, the activation of STATs is tightly regulated. In cancer, by contrast, STAT proteins, particularly STAT3 and STAT5, become activated constitutively, thereby driving the malignant phenotype of cancer cells. Since these proteins are largely dispensable in the function of normal adult cells, STATs represent a potentially important target for cancer therapy. Although transcription factors have traditionally been viewed as suboptimal targets for pharmacological inhibition, chemical biology approaches have been particularly fruitful in identifying compounds that can modulate this pathway through a variety of mechanisms. STAT inhibitors have notable anti-cancer effects in many tumor systems, show synergy with other therapeutic modalities, and have the potential to eradicate tumor stem cells. Furthermore, STAT inhibitors identified through the screening of chemical libraries can then be employed in large scale analyses such as gene expression profiling, RNA interference screens, or large-scale tumor cell line profiling. Data derived from these studies can then provide key insights into mechanisms of STAT signal transduction, as well as inform the rational design of targeted therapeutic strategies for cancer patients

    Laboratory Simulations of Mars Evaporite Geochemistry

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    Evaporite-rich sedimentary deposits on Mars were formed under chemical conditions quite different from those on Earth. Their unique chemistries record the chemical and aqueous conditions under which they were formed and possibly subsequent conditions to which they were subjected. We have produced evaporite salt mineral suites in the laboratory under two simulated Martian atmospheres: (1) present-day and (2) a model of an ancient Matian atmosphere rich in volcanic gases. The composition of these synthetic Mars evaporites depends on the atmospheres under which they were desiccated as well as the chemistries of their precursor brines. In this report, we describe a Mars analog evaporite laboratory apparatus and the experimental methods we used to produce and analyze the evaporite mineral suites

    Bonded Cumomer Analysis of Human Melanoma Metabolism Monitored by 13C NMR Spectroscopy of Perfused Tumor Cells.

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    A network model for the determination of tumor metabolic fluxes from (13)C NMR kinetic isotopomer data has been developed and validated with perfused human DB-1 melanoma cells carrying the BRAF V600E mutation, which promotes oxidative metabolism. The model generated in the bonded cumomer formalism describes key pathways of tumor intermediary metabolism and yields dynamic curves for positional isotopic enrichment and spin-spin multiplets. Cells attached to microcarrier beads were perfused with 26 mm [1,6-(13)C2]glucose under normoxic conditions at 37 ¬įC and monitored by (13)C NMR spectroscopy. Excellent agreement between model-predicted and experimentally measured values of the rates of oxygen and glucose consumption, lactate production, and glutamate pool size validated the model. ATP production by glycolytic and oxidative metabolism were compared under hyperglycemic normoxic conditions; 51% of the energy came from oxidative phosphorylation and 49% came from glycolysis. Even though the rate of glutamine uptake was ‚ąľ50% of the tricarboxylic acid cycle flux, the rate of ATP production from glutamine was essentially zero (no glutaminolysis). De novo fatty acid production was ‚ąľ6% of the tricarboxylic acid cycle flux. The oxidative pentose phosphate pathway flux was 3.6% of glycolysis, and three non-oxidative pentose phosphate pathway exchange fluxes were calculated. Mass spectrometry was then used to compare fluxes through various pathways under hyperglycemic (26 mm) and euglycemic (5 mm) conditions. Under euglycemic conditions glutamine uptake doubled, but ATP production from glutamine did not significantly change. A new parameter measuring the Warburg effect (the ratio of lactate production flux to pyruvate influx through the mitochondrial pyruvate carrier) was calculated to be 21, close to upper limit of oxidative metabolism

    Documenting Pressures Used for Manual Diagnosis and Treatment of Cervical Spine Somatic Dysfunction

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    Background: Palpatory assessment of free or restricted motion patterns is part of the diagnosis of spinal somatic dysfunction (SD). Diagnostically, local soft tissues are compressed (pre-loaded) over the structure of interest followed by one or more test impulses to assess the quality of the ‚Äúend-feel‚ÄĚ motion in several planes. These barrier sensations are often described qualitatively but have not been objectively quantified. Noninvasive, tactile pressure sensors built into a digital palpation monitoring system (IsoTOUCH¬ģ; Neuromuscular Engineering; Nashville TN, USA) were used to document loading and impulse pressures for palpatory segmental diagnosis and to first engage and then quickly move through a restrictive SD barrier using an osteopathic manipulative treatment (OMT) technique

    Defining epitope coverage requirements for T cell-based HIV vaccines: Theoretical considerations and practical applications

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    <p>Abstract</p> <p>Background</p> <p>HIV vaccine development must address the genetic diversity and plasticity of the virus that permits the presentation of diverse genetic forms to the immune system and subsequent escape from immune pressure. Assessment of potential HIV strain coverage by candidate T cell-based vaccines (whether natural sequence or computationally optimized products) is now a critical component in interpreting candidate vaccine suitability.</p> <p>Methods</p> <p>We have utilized an N-mer identity algorithm to represent T cell epitopes and explore potential coverage of the global HIV pandemic using natural sequences derived from candidate HIV vaccines. Breadth (the number of T cell epitopes generated) and depth (the variant coverage within a T cell epitope) analyses have been incorporated into the model to explore vaccine coverage requirements in terms of the number of discrete T cell epitopes generated.</p> <p>Results</p> <p>We show that when multiple epitope generation by a vaccine product is considered a far more nuanced appraisal of the potential HIV strain coverage of the vaccine product emerges. By considering epitope breadth and depth several important observations were made: (1) epitope breadth requirements to reach particular levels of vaccine coverage, even for natural sequence-based vaccine products is not necessarily an intractable problem for the immune system; (2) increasing the valency (number of T cell epitope variants present) of vaccine products dramatically decreases the epitope requirements to reach particular coverage levels for any epidemic; (3) considering multiple-hit models (more than one exact epitope match with an incoming HIV strain) places a significantly higher requirement upon epitope breadth in order to reach a given level of coverage, to the point where low valency natural sequence based products would not practically be able to generate sufficient epitopes.</p> <p>Conclusions</p> <p>When HIV vaccine sequences are compared against datasets of potential incoming viruses important metrics such as the minimum epitope count required to reach a desired level of coverage can be easily calculated. We propose that such analyses can be applied early in the planning stages and during the execution phase of a vaccine trial to explore theoretical and empirical suitability of a vaccine product to a particular epidemic setting.</p

    Old and New Fields on Super Riemann Surfaces

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    The ``new fields" or ``superconformal functions" on N=1N=1 super Riemann surfaces introduced recently by Rogers and Langer are shown to coincide with the Abelian differentials (plus constants), viewed as a subset of the functions on the associated N=2N=2 super Riemann surface. We confirm that, as originally defined, they do not form a super vector space.Comment: 9 pages, LaTex. Published version: minor changes for clarity, two new reference

    Influence of coral and algal exudates on microbially mediated reef metabolism.

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    Benthic primary producers in tropical reef ecosystems can alter biogeochemical cycling and microbial processes in the surrounding seawater. In order to quantify these influences, we measured rates of photosynthesis, respiration, and dissolved organic carbon (DOC) exudate release by the dominant benthic primary producers (calcifying and non-calcifying macroalgae, turf-algae and corals) on reefs of Mo'orea French Polynesia. Subsequently, we examined planktonic and benthic microbial community response to these dissolved exudates by measuring bacterial growth rates and oxygen and DOC fluxes in dark and daylight incubation experiments. All benthic primary producers exuded significant quantities of DOC (roughly 10% of their daily fixed carbon) into the surrounding water over a diurnal cycle. The microbial community responses were dependent upon the source of the exudates and whether the inoculum of microbes included planktonic or planktonic plus benthic communities. The planktonic and benthic microbial communities in the unamended control treatments exhibited opposing influences on DO concentration where respiration dominated in treatments comprised solely of plankton and autotrophy dominated in treatments with benthic plus plankon microbial communities. Coral exudates (and associated inorganic nutrients) caused a shift towards a net autotrophic microbial metabolism by increasing the net production of oxygen by the benthic and decreasing the net consumption of oxygen by the planktonic microbial community. In contrast, the addition of algal exudates decreased the net primary production by the benthic communities and increased the net consumption of oxygen by the planktonic microbial community thereby resulting in a shift towards net heterotrophic community metabolism. When scaled up to the reef habitat, exudate-induced effects on microbial respiration did not outweigh the high oxygen production rates of benthic algae, such that reef areas dominated with benthic primary producers were always estimated to be net autotrophic. However, estimates of microbial consumption of DOC at the reef scale surpassed the DOC exudation rates suggesting net consumption of DOC at the reef-scale. In situ mesocosm experiments using custom-made benthic chambers placed over different types of benthic communities exhibited identical trends to those found in incubation experiments. Here we provide the first comprehensive dataset examining direct primary producer-induced, and indirect microbially mediated alterations of elemental cycling in both benthic and planktonic reef environments over diurnal cycles. Our results highlight the variability of the influence of different benthic primary producers on microbial metabolism in reef ecosystems and the potential implications for energy transfer to higher trophic levels during shifts from coral to algal dominance on reefs

    Apollo Lightcraft Project

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    The ultimate goal for this NASA/USRA-sponsored Apollo Lightcraft Project is to develop a revolutionary manned launch vehicle technology which can potentially reduce payload transport costs by a factor of 1000 below the Space Shuttle Orbiter. The Rensselaer design team proposes to utilize advanced, highly energetic, beamed-energy sources (laser, microwave) and innovative combined-cycle (airbreathing/rocket) engines to accomplish this goal. The research effort focuses on the concept of a 100 MW-class, laser-boosted Lightcraft Technology Demonstrator (LTD) drone. The preliminary conceptual design of this 1.4 meter diameter microspacecraft involved an analytical performance analysis of the transatmospheric engine in its two modes of operation (including an assessment of propellant and tankage requirements), and a detailed design of internal structure and external aeroshell configuration. The central theme of this advanced propulsion research was to pick a known excellent working fluid (i.e., air or LN sub 2), and then to design a combined-cycle engine concept around it. Also, a structural vibration analysis was performed on the annular shroud pulsejet engine. Finally, the sensor satellite mission was examined to identify the requisite subsystem hardware: e.g., electrical power supply, optics and sensors, communications and attitude control systems
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