Thionaphthen isosteres of biologically active indole derivatives

This Thesis is a report of an investigation into the preparation of thionaphthen isosteres of biologically active indole compounds . The introduction deals with the theoretical implications of the various approaches to the syntheses of biologically active compounds, and in particular those with an indole nucleus present in the molecule. A review on "Biological Activity in Compounds Possessing Thiophen Rings" is included, and justification is provided for the preparation of thionaphthen isosteres of such compounds as 5-hydroxytryptamine. In section 1, the position of electrophilic substitution in 5-substituted thionaphthens was investigated with a view to employing the various protecting groups in a synthesis of the thionaphthen analogue of 5-hydroxy-tryptamine. Other interesting orientation effects are also reported. Section 2 deals with the preparation of various thionaphthen derivatives containing a gramine side-chain as possible antagonists of adrenaline and of 5-hydroxy-tryptamine. In section 3, attempts to prepare 3-(2'-amino ethyl)-5-hydroxythionaphthen, the thionaphthen analogue of 5-hydroxytryptamine, are reported. Various other isosteres of hydroxtrytryptamine-like compounds including 3-(2'-amino ethyl)-6-hydroxy-thionaphthen are reported. Section also deals with the syntheses of thionsphthen analogues of harmine and harmaline

GAP ANALYSIS OF DEPARTMENT OF DEFENSE PROGRAM MANAGEMENT COMPETENCY STANDARDS IN PREPARATION FOR THE SHIFT TO PORTFOLIO MANAGEMENT IN DEFENSE ACQUISITIONS

The purpose of this study is to perform a gap analysis on the existing Department of Defense (DOD) program management competency standards to determine if changes are required to fully adopt product portfolio management (PPM) strategies in defense acquisitions. We do this by comparing the current DOD standards to the Project Management Institute's Portfolio Management Professional certification standards. We ask where the gaps in the standards exist and where the standards align, and assign a Barrier to Implementation (BTI) score to each gap in the DOD standard. The study found that the DOD is on average 41% aligned with industry standards. In the higher weighted domains of Governance and Strategic Alignment, alignment percentages are significantly lower. The composite BTI score for the DOD is 1.45, indicating low to medium BTIs for most of the gaps. Results do not suggest that the DOD is incapable of conducting PPM, but rather that the current competency standards do not align with industry best practices. Defense acquisitions professionals should review our analysis and formulate Portfolio Management Career Field Functional Competencies to further professional standards, develop the necessary job skills and evaluation criteria, and further the process of achieving congressional mandates for portfolio management implementation.Outstanding ThesisMajor, United States Marine CorpsMajor, United States Marine CorpsMajor, United States Marine CorpsApproved for public release. Distribution is unlimited

Heat Transfer and Pressure Drop in Concentric Annular Flows of Binary Inert Gas Mixtures

Studies of heat transfer and pressure drop of binary inert gas mixtures flowing through smooth concentric circular annuli, tubes with fully developed velocity profiles, and constant heating rate are described. There is a general lack of agreement among the constant property heat transfer correlations for such mixtures. No inert gas mixture data exist for annular channels. The intent of this study was to develop highly accurate and benchmarked pressure drop and heat transfer correlations that can be used to size heat exchangers and cores for direct gas Brayton nuclear power plants. The inside surface of the annular channel is heated while the outer surface of the channel is insulated. Annulus ratios range 0.5 < r* < 0.83. These smooth tube data may serve as a reference to the heat transfer and pressure drop performance in annuli, tubes, and channels having helixes or spacer ribs, or other surfaces

Program Management versus Portfolio Management in Defense Acquisition

Program Management / Faculty ReportAcquisition Research Program Sponsored Report SeriesSponsored Acquisition Research & Technical ReportsThis research performed a gap analysis on the existing Department of Defense (DoD) program management competency standards to determine if changes are required to fully adopt product portfolio management (PPM) strategies in defense acquisition. Current DoD program management standards are compared to the Project Management Institute's Portfolio Management Professional certification standards to analyze alignment and gaps between the standards. Barrier to Implementation (BTI) scores are assigned to address the identified gaps in the DoD standard. The study found that the DoD program management competencies are on average 41% aligned with portfolio management industry standards. The DoD program management competencies are least aligned with the portfolio management domains of governance and strategic alignment. The composite BTI score indicates low to medium level of implementation barriers for most of the gaps. Results indicate that the DoD is capable of conducting PPM, and further research is needed to fully align the current competency standards with industry best practices. Defense acquisition senior leaders should consider formulating DoD portfolio management career field functional competencies to address congressional mandates for portfolio management implementation within the DoD.Approved for public release; distribution is unlimited

Design of Refractory Metal Heat Pipe Life Test Environment Chamber, Cooling System, and Radio Frequency Heating System

A series of 16 Mo-44.5%Re alloy/sodium heat pipes will be experimentally tested to examine heat pipe aging. To support this evaluation, an environmental test chamber and a number of auxiliary subsystems are required. These subsystems include radio frequency (RF) power supplies/inductive coils, recirculation water coolant loops, and chamber gas conditioning. The heat pipes will be grouped, based on like power and gas mixture requirements, into three clusters of five units each, configured in a pentagonal arrangement. The highest powered heat pipe will be tested separately. Test chamber atmospheric purity is targeted at <0.3 ppb oxygen at an approximate operating pressure of 76 torr (.1.5 psia), maintained by active purification (oxygen level is comparable to a 10(exp -6) torr environment). Treated water will be used in two independent cooling circuits to remove .85 kW. One circuit will service the RF hardware while the other will maintain the heat pipe calorimetry. Initial procedures for the startup and operation of support systems have been identified. Each of these subsystems is outfitted with a variety of instrumentation, integrated with distributed real-time controllers and computers. A local area network provides communication between all devices. This data and control network continuously monitors the health of the test hardware, providing warning indicators followed by automatic shutdown should potentially damaging conditions develop. During hardware construction, a number of checkout tests.many making use of stainless steel prototype heat pipes that are already fabricated.will be required to verify operation

Influence of Gamma-Ray Emission on the Isotopic Composition of Clouds in the Interstellar Medium

We investigate one mechanism of the change in the isotopic composition of cosmologically distant clouds of interstellar gas whose matter was subjected only slightly to star formation processes. According to the standard cosmological model, the isotopic composition of the gas in such clouds was formed at the epoch of Big Bang nucleosynthesis and is determined only by the baryon density in the Universe. The dispersion in the available cloud composition observations exceeds the errors of individual measurements. This may indicate that there are mechanisms of the change in the composition of matter in the Universe after the completion of Big Bang nucleosynthesis. We have calculated the destruction and production rates of light isotopes (D, 3He, 4He) under the influence of photonuclear reactions triggered by the gamma-ray emission from active galactic nuclei (AGNs). We investigate the destruction and production of light elements depending on the spectral characteristics of the gamma-ray emission. We show that in comparison with previous works, taking into account the influence of spectral hardness on the photonuclear reaction rates can increase the characteristic radii of influence of the gamma-ray emission from AGNs by a factor of 2-8. The high gamma-ray luminosities of AGNs observed in recent years increase the previous estimates of the characteristic radii by two orders of magnitude. This may suggest that the influence of the emission from AGNs on the change in the composition of the medium in the immediate neighborhood (the host galaxy) has been underestimated.Comment: 13 pages, 13 figures, 3 table

Gap symmetry and structure of Fe-based superconductors

The recently discovered Fe-pnictide and chalcogenide superconductors display low-temperature properties suggesting superconducting gap structures which appear to vary substantially from family to family, and even within families as a function of doping or pressure. We propose that this apparent nonuniversality can actually be understood by considering the predictions of spin fluctuation theory and accounting for the peculiar electronic structure of these systems, coupled with the likely 'sign-changing s-wave' (s\pm) symmetry. We review theoretical aspects, materials properties and experimental evidence relevant to this suggestion, and discuss which further measurements would be useful to settle these issues.Comment: 86 pages, revie

A primary care, multi-disciplinary disease management program for opioid-treated patients with chronic non-cancer pain and a high burden of psychiatric comorbidity

BACKGROUND: Chronic non-cancer pain is a common problem that is often accompanied by psychiatric comorbidity and disability. The effectiveness of a multi-disciplinary pain management program was tested in a 3 month before and after trial. METHODS: Providers in an academic general medicine clinic referred patients with chronic non-cancer pain for participation in a program that combined the skills of internists, clinical pharmacists, and a psychiatrist. Patients were either receiving opioids or being considered for opioid therapy. The intervention consisted of structured clinical assessments, monthly follow-up, pain contracts, medication titration, and psychiatric consultation. Pain, mood, and function were assessed at baseline and 3 months using the Brief Pain Inventory (BPI), the Center for Epidemiological Studies-Depression Scale scale (CESD) and the Pain Disability Index (PDI). Patients were monitored for substance misuse. RESULTS: Eighty-five patients were enrolled. Mean age was 51 years, 60% were male, 78% were Caucasian, and 93% were receiving opioids. Baseline average pain was 6.5 on an 11 point scale. The average CESD score was 24.0, and the mean PDI score was 47.0. Sixty-three patients (73%) completed 3 month follow-up. Fifteen withdrew from the program after identification of substance misuse. Among those completing 3 month follow-up, the average pain score improved to 5.5 (p = 0.003). The mean PDI score improved to 39.3 (p < 0.001). Mean CESD score was reduced to 18.0 (p < 0.001), and the proportion of depressed patients fell from 79% to 54% (p = 0.003). Substance misuse was identified in 27 patients (32%). CONCLUSIONS: A primary care disease management program improved pain, depression, and disability scores over three months in a cohort of opioid-treated patients with chronic non-cancer pain. Substance misuse and depression were common, and many patients who had substance misuse identified left the program when they were no longer prescribed opioids. Effective care of patients with chronic pain should include rigorous assessment and treatment of these comorbid disorders and intensive efforts to insure follow up

Do not attempt resuscitation decisions in a cancer centre: addressing difficult ethical and communication issues

Talking to patients about ‘Do Not Attempt Resuscitation’ decisions is difficult for many doctors. Communication about ‘Do Not Attempt Resuscitation’ decisions should occur as part of a wider discussion of treatment goals at an earlier stage in the patient's illness. A doctor should not initiate any treatment, including cardio-pulmonary resuscitation if he/she does not believe it will benefit the patient. An ethical framework is offered which may be of practical help in clarifying decision-making