Federal highway spending and economic growth in Appalachia

Appalachia has always struggled economically due to three main factors: absentee ownership, isolation, and stereotyping. In 1965, Congress created the Appalachian Regional Commission with the mission of providing economic development programs to increase development in the region. Federal highway spending was seen as a key to improving the Appalachian infrastructure.;Today, the debate continues on the effectiveness of federal highway spending in Appalachia. The purpose of this study is to examine the effects of federal highway spending on socioeconomic status in Appalachia by analyzing the effects of spending during an economic recovery from 1983--89 and recession 1989--92. Three constructs determine increases in socioeconomic status: per capita income growth, civilian employment growth, and non-farm employment growth.;The data indicates that federal highway spending in Appalachia has little to no effect on increasing socioeconomic status in the region. The most important factor indicating current growth in Appalachia is growth during the previous economic cycle

Judicial Review of Antitrust Consent Decrees: Reconciling Judicial Responsibility with Executive Discretion

For nearly eighty years the Department of Justice has disposed of civil antitrust suits through settlement negotiations followed by entry of a consent decree. Though not expressly authorized by statute, the Supreme Court has affirmed the use of this powerful enforcement tool. In 1974, Congress enacted the Antitrust Procedures and Penalties Act (APPA), which includes a provision that district court judges must determine if a proposed consent decree is in the public interest before entering it. This Note analyzes the standards applied by the courts in their review of consent decrees before the enactment of the APPA. the congressional intent in passing the legislation, and the standards that courts have applied since its enactment-focusing on the unclear staidard for making the public interest determination. The Note explores the implications of the new and ill-advised standard applied by the district court in United States v. American Telephone & Telegraph Co. In concluding that the cases have not yet established a satisfactory analytical formula for reviewing consent decrees, the Note proposes a workable standard of review that will allow the courts to simultaneously make an independent determination that the proposed decree is in the public interest, preserve the consent decree as a viable enforcement tool, and accord the Department of Justice the discretion it needs to enforce the antitrust laws

Working towards a more sustainable NHS: Exploring the role of GPs through survey and interviews

This study examined how GPs in Wiltshire understood sustainable development and its implications for the NHS, their role as GPs and the factors that influenced their engagement with sustainability through an online survey followed by one to one qualitative interviews. The objectives were to better understand how GPs in Wiltshire understood sustainability, to identify gaps between the literature and GPs and to determine the factors that influenced the engagement of GPs with sustainability. The NHS has committed to more sustainable practices, setting a target of an 80% reduction in greenhouse gas emissions by 2050, which will require radical change in how healthcare is delivered. Proposals on how to achieve the radical transition to more sustainable NHS are emerging in a developing literature on sustainability, health and healthcare. However there is a knowledge gap as to the extent that the analysis of sustainable development and the NHS and proposals for a more sustainable NHS are shared by a broad section of health professionals.The findings indicated that research participants had complex and nuanced views towards sustainability and the NHS. Findings suggested broad levels of support for some sustainability, activities such as building the resilience of individuals and local communities alongside reservations about others such as taking environmental impact into account when making clinical decisions. Findings also provide a potential explanation of why this broad support may not motivate change. Interview and survey data that suggested that sustainability was remote or an afterthought provide an indication of the leadership, resources and guidance necessary to change practices. The study contributes new knowledge about how this vital group of health professionals understand and engage with sustainability. The study suggests that sustainability should be communicated in terms of improvement in healthcare and the future viability of the NHS alongside clear commitments to sustainability in terms of leadership, strategic integration and organisational incentives

Preformulation solid-state supramolecular beneficiation of selected active pharmaceutical ingredients and a novel drug candidate

The aim from the outset of the project on which this thesis is based was to make use of contemporary methods in the field of supramolecular chemistry to improve the suboptimal physicochemical properties of selected compounds for use in the formulation of pharmaceutical products. The compounds selected were: Clevudine, an established drug that is currently in use for the treatment of chronic hepatitis B infections, 6-(3- (Methylsulfonyl)phenyl)-3-(4-(methylsulfonyl)phenyl)-imidazo[1,2-b]pyridazine (MMV652103), a novel antimalarial drug candidate that displayed good in vitro potency against multidrug resistant and sensitive plasmodial strains and ()-α-lipoamide, a bioactive antioxidant that is currently in use for the clinical treatment of diabetic neuropathy and has other potential uses e.g. as an antiretroviral agent. The methods utilised in pursuit of novel solid-state forms of the compounds included a combination of crystal engineering and experimental screening for polymorphs, solvates/hydrates, cyclodextrin (CD) inclusion complexes, pharmaceutical salts and co-crystals. Screening involved grinding and co-precipitation methods. Characterisation of new forms involved thermal analytical methods including hot stage microscopy (HSM), differential thermal analysis (DTA), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and variable temperature powder X-ray diffraction (VTPXRD). In all cases where single-crystals of adequate quality and size were successfully prepared, the crystal structures were elucidated by single-crystal X-ray diffraction. Molecular conformations, inter- and intramolecular interactions and packing arrangements of crystals were characterised. Polymorphism of clevudine was addressed for the first time. Three polymorphs of clevudine were isolated and characterised in terms of crystal structures and thermal behaviour. The solubility and thermodynamic stability ranking of the three forms was established and schematic energy-temperature diagrams were constructed through the use of the thermal methods listed above, solvent-mediated transition experiments and by kinetic solubility experiments. Characterisation by infrared (IR) spectroscopy has made it possible to promptly and effortlessly identify each form. Multiple novel solid-state forms of the antimalarial drug candidate MMV652103 were produced including four polymorphs, a hydrate, five co-crystals and a salt. The solubility and thermodynamic stability ranking of the polymorphs was established through thermal analysis and kinetic solubility experiments. An amorphous form showed an improvement in dissolution rate, with a concentration 3-4 times that of the crystalline forms after one hour. The designation as co-crystals or salts was accomplished through the use of single crystal X-ray structural analysis and confirmed by IR spectroscopy. Stoichiometry was determined by 1 H - nuclear magnetic resonance (NMR) spectroscopy. A customised solubility experiment was carried out to compare the dissolution rates of the various multi-component forms of MMV652103 in an environment simulating the human duodenum. An enhancement of the dissolution rate was observed with a maximum concentration 4.7 times higher for the co-crystal than for the untreated active compound. Inclusion complexation of ()-α-lipoamide with native CDs (α-, β-, and γ-CD) was confirmed by comparison of putative PXRD traces with those of known isostructural series. Novel complexes were synthesised with the above mentioned native CDs as well as with three derivatised CDs (TRIMEA, DIMEB and TRIMEB). The crystal structures were characterised by single-crystal X-ray diffraction. Host-guest stoichiometries were determined by 1 H-NMR spectroscopy and validated by the ratio of mass loss through TGA. Water composition, melting points and thermal stability in terms of decomposition and guest loss temperatures of the complexes were determined by means of the appropriate thermal methods (DTA, TGA, DSC, HSM). Phase solubility experiments were carried out and showed solubility enhancements for the bioactive compound ranging from a 1.8 fold increase with α-CD to a 7.4 fold increase with randomly methylated β-CD

The Effects of Federal Spending on Earnings Change in Appalachia

In this paper we investigate the effects of federal spending on earnings change in Appalachian counties during the 1983-88 recovery and 1989-92 recession. Specifically, we explore the effects of federal spending from grants/research, procurement, salary/wages and defense. The analysis controls for key concepts in the human ecology and new urban sociology. The dependent variables are earnings change for each business cycle from a shift-share analysis, which decomposes county earnings change into that from nationally declining industries. The analysis shows that federal spending has no effect on earnings change, when it is considered as an aggregate measure. However, when federal spending is reclassified into the four categories, spending for grants/research has a positive effect on both measures of earnings change in the 1982-88 recovery. Moreover, the effects of grants/research spending are dependent upon the education level of the county population. However, education by grants/research interaction effect is specific to nonmetro counties in Appalachia. Implications for future research are discussed

Teachers Learning: Engagement, Identity, and Agency in Powerful Professional Development

Professional development (PD) is seen by a broad cross-section of stakeholders — teachers, principals, policymakers — as essential for instructional improvement and student learning. And yet, despite deep investments of time and money in its design and implementation, the return on investment and subjective assessments about PD’s effectiveness remain uneven. In this thesis, I focus in-depth on professional development experiences that teachers identify as their most powerful and ask what these experiences could suggest toward improving PD design, policy, and research. Specifically, drawing on 25 in-depth accounts of powerful professional learning, I analyze PD across three papers, each of which applies a distinct analytical lens. First, using self-determination theory (Deci and Ryan, 1985, 2000), I explore the extent to which powerful learning experiences help to satisfy the three basic psychological needs of autonomy, competence, and relatedness. Second, using the growing body literature on professional identity (e.g., Beijaard et al., 2004), I posit that teachers may be motivated to pursue professional learning experiences that align with their core beliefs and identity. Extending this literature, I elaborate three distinct conceptions of how identity interacts with PD: an affinity for the what (content), the who (facilitation), and the with whom (community). I similarly discuss ways that powerful learning may help to form or transform teacher identity. Third, observing a pattern in the data and drawing on emerging literature on teacher agency (e.g., Priestley et al., 2015), I define teacher agency in professional learning as a multi-dimensional construct – agency over, during, and emerging from PD – and analyze the extent to which each dimension was evident in powerful and contrastingly negative professional learning experiences. I conclude that increasing dimensions of agency may be a promising lever for improving professional learning at both an individual and system level.Finally, by privileging teachers’ unique perspectives and emphasizing the deeply subjective nature of learning, this thesis aims both to complement and complicate the existing research on PD design and effectiveness and the policy imperative for scale

The design of a high efficiency RF power amplifier for an MCM process

Thesis (M. Eng.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2005.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.Includes bibliographical references (p. 91-92).In this thesis, I addressed issues arising in the design of a high efficiency RF power amplifier for the Draper Laboratory multi-chip module (MCM) process. A design for a 2.3 GHz PCB amplifier using an enhancement-mode pHEMT device that achieves 68.9% PAE at 30 dBm output power is presented. Analysis of heat management, die connection parasitics, and transmission line structures in the context of the MCM process is performed to show that a similar design could realistically be adapted to the MCM process with possible performance enhancement.by James Noonan.M.Eng

The C-terminal domain of the Bloom syndrome DNA helicase is essential for genomic stability

BACKGROUND: Bloom syndrome is a rare cancer-prone disorder in which the cells of affected persons have a high frequency of somatic mutation and genomic instability. Bloom syndrome cells have a distinctive high frequency of sister chromatid exchange and quadriradial formation. BLM, the protein altered in BS, is a member of the RecQ DNA helicase family, whose members share an average of 40% identity in the helicase domain and have divergent N-terminal and C-terminal flanking regions of variable lengths. The BLM DNA helicase has been shown to localize to the ND10 (nuclear domain 10) or PML (promyelocytic leukemia) nuclear bodies, where it associates with TOPIIIα, and to the nucleolus. RESULTS: This report demonstrates that the N-terminal domain of BLM is responsible for localization of the protein to the nuclear bodies, while the C-terminal domain directs the protein to the nucleolus. Deletions of the N-terminal domain of BLM have little effect on sister chromatid exchange frequency and chromosome stability as compared to helicase and C-terminal mutations which can increase SCE frequency and chromosome abnormalities. CONCLUSION: The helicase activity and the C-terminal domain of BLM are critical for maintaining genomic stability as measured by the sister chromatid exchange assay. The localization of BLM into the nucleolus by the C-terminal domain appears to be more important to genomic stability than localization in the nuclear bodies

Genomic correlates of relationship QTL involved in fore-versus hind limb divergence in mice

Divergence of serially homologous elements of organisms is a common evolutionary pattern contributing to increased phenotypic complexity. Here, we study the genomic intervals affecting the variational independence of fore- and hind limb traits within an experimental mouse population. We use an advanced intercross of inbred mouse strains to map the loci associated with the degree of autonomy between fore- and hind limb long bone lengths (loci affecting the relationship between traits, relationship quantitative trait loci [rQTL]). These loci have been proposed to interact locally with the products of pleiotropic genes, thereby freeing the local trait from the variational constraint due to pleiotropic mutations. Using the known polymorphisms (single nucleotide polymorphisms [SNPs]) between the parental strains, we characterized and compared the genomic regions in which the rQTL, as well as their interaction partners (intQTL), reside. We find that these two classes of QTL intervals harbor different kinds of molecular variation. SNPs in rQTL intervals more frequently reside in limb-specific cis-regulatory regions than SNPs in intQTL intervals. The intQTL loci modified by the rQTL, in contrast, show the signature of protein-coding variation. This result is consistent with the widely accepted view that protein-coding mutations have broader pleiotropic effects than cis-regulatory polymorphisms. For both types of QTL intervals, the underlying candidate genes are enriched for genes involved in protein binding. This finding suggests that rQTL effects are caused by local interactions among the products of the causal genes harbored in rQTL and intQTL intervals. This is the first study to systematically document the population-level molecular variation underlying the evolution of character individuation