The Great Divide: The Political Implications of Southern Regional Identification in Kentucky

Kentucky occupies a unique place on the American political landscape. The Commonwealth has never been fully embraced as Southern by most observers, but at the same time it is not necessarily a Northern state. As the intersection of North and South in the United States, Kentucky presentes a unique opportunity to study the impact of regional identity on public opinion. Utilizing data from a 2014 survey of a random sample of Kentucky residents, we are able to demonstrate that Southern regional identification is fairly high in Kentucky, and that this identification has a significant influence on opinion regard politicians and policy preferences in Kentucky

Thoroughbred Horse Racing and Breeding as a Tax Sheltered Investment: Recent Tax Law Developments

This comment will first discuss principal tax shelter methods in general terms and then address the effects of recent tax legislation on tax-sheltered investments. Finally, the application of the current rules to hypothetical thoroughbred tax-sheltered investments will be undertaken to illustrate some of the options available to investors

Assembly and Activation of Alternative Complement Components on Endothelial Cell-Anchored Ultra-Large Von Willebrand Factor Links Complement and Hemostasis-Thrombosis

Background: Vascular endothelial cells (ECs) express and release protein components of the complement pathways, as well as secreting and anchoring ultra-large von Willebrand factor (ULVWF) multimers in long string-like structures that initiate platelet adhesion during hemostasis and thrombosis. The alternative complement pathway (AP) is an important nonantibody- requiring host defense system. Thrombotic microangiopathies can be associated with defective regulation of the AP (atypical hemolytic-uremic syndrome) or with inadequate cleavage by ADAMTS-13 of ULVWF multimeric strings secreted by/anchored to ECs (thrombotic thrombocytopenic purpura). Our goal was to determine if EC-anchored ULVWF strings caused the assembly and activation of AP components, thereby linking two essential defense mechanisms. Methodology/Principal Findings: We quantified gene expression of these complement components in cultured human umbilical vein endothelial cells (HUVECs) by real-time PCR: C3 and C5; complement factor (CF) B, CFD, CFP, CFH and CFI of the AP; and C4 of the classical and lectin (but not alternative) complement pathways. We used fluorescent microscopy, monospecific antibodies against complement components, fluorescent secondary antibodies, and the analysis of .150 images to quantify the attachment of HUVEC-released complement proteins to ULVWF strings secreted by, and anchored to, the HUVECs (under conditions of ADAMTS-13 inhibition). We found that HUVEC-released C4 did not attach to ULVWF strings, ruling out activation of the classical and lectin pathways by the strings. In contrast, C3, FB, FD, FP and C5, FH and FI attached to ULVWF strings in quantitative patterns consistent with assembly of the AP components into active complexes. This was verified when non-functional FB blocked the formation of AP C3 convertase complexes (C3bBb) on ULVWF strings. Conclusions/Significance: AP components are assembled and activated on EC-secreted/anchored ULVWF multimeric strings. Our findings provide one possible molecular mechanism for clinical linkage between different types of thrombotic and complement-mediated disorders

Orbital magnetoelectric coupling in band insulators

Magnetoelectric responses are a fundamental characteristic of materials that break time-reversal and inversion symmetries (notably multiferroics) and, remarkably, of "topological insulators" in which those symmetries are unbroken. Previous work has shown how to compute spin and lattice contributions to the magnetoelectric tensor. Here we solve the problem of orbital contributions by computing the frozen-lattice electronic polarization induced by a magnetic field. One part of this response (the "Chern-Simons term") can appear even in time-reversal-symmetric materials and has been previously shown to be quantized in topological insulators. In general materials there are additional orbital contributions to all parts of the magnetoelectric tensor; these vanish in topological insulators by symmetry and also vanish in several simplified models without time-reversal and inversion those magnetoelectric couplings were studied before. We give two derivations of the response formula, one based on a uniform magnetic field and one based on extrapolation of a long-wavelength magnetic field, and discuss some of the consequences of this formula.Comment: 13 page

Direct Current Electrical Stimulation Increases the Fusion Rate of Spinal Fusion Cages

Study Design. A randomized experimental evaluation of direct current stimulation in a validated animal model with an experimental control group, using blinded radiographic, biomechanical, histologic, and statistical measures. Objectives. To evaluate the efficacy of the adjunctive use of direct current stimulation on the fusion rate and speed of healing of titanium interbody fusion cages packed with autograft in a sheep lumbar interbody fusion model. Summary of Background Data. Titanium lumbar interbody spinal fusion cages have been reported to be 90% effective for single-level lumbar interbody fusion. However, fusion rates are reported to be between 70% and 80% in patients with multilevel fusions or with risk factors such as obesity, tobacco use, or metabolic disorders. The authors hypothesized that direct current stimulation would increase the fusion rate of titanium interbody fusion cages packed with autograft in a sheep lumbar interbody fusion model. Methods. Twenty-two sheep underwent lumbar discectomy and fusion at L4–L5 with an 11- × 20-mm Bagby and Kuslich (BAK) cage packed with autograft. Seven sheep received a BAK cage and no current. Seven sheep had a cage and a 40-μA current applied with a direct current stimulator. Eight sheep had a BAK cage and a 100-μA current applied. All sheep were killed 4 months after surgery. The efficacy of electrical stimulation in promoting interbody fusion was assessed by performing radiographic, biomechanical, and histologic analyses in a blinded fashion. Results. The histologic fusion rate increased as the direct current dose increased from 0 μA to 40 μA to 100 μA (P \u3c 0.009). Histologically, all animals in the 100-μA group had fusions in both the right and left sides of the cage. Direct current stimulation had a significant effect on increasing the stiffness of the treated motion segment in right lateral bending (P \u3c 0.120), left lateral bending (P \u3c 0.017), right axial rotation (P \u3c 0.004), left axial rotation (P \u3c 0.073), extension (P \u3c 0.078), and flexion (P \u3c 0.029) over nonstimulated levels. Conclusion. Direct current stimulation increased the histologic and biomechanical fusion rate and the speed of healing of lumbar interbody spinal fusion cages in an ovine model at 4 months

Polypeptides, Systems, and Methods Useful for Detecting Glucose

The presently-disclosed subject matter provides biosensors for detecting molecules of interest. The biosensors include a polypeptide capable of selectively-binding glucose, wherein the polypeptide molecule is selected from: an unnatural analogue of wild type glucose binding protein; a fragment of wild type glucose binding protein; and an unnatural analogue fragment of wild type glucose binding protein

Probing a Promiscuous Binding Pocket of the Proteasome

The proteasome is a multi-catalytic protease complex responsible for the degradation of unneeded, damaged or misfolded proteins. The proteasome is a validated target for the treatment of haematological malignancies such as multiple myeloma and mantle cell lymphoma, as demonstrated by the FDA approved proteasome inhibitors bortezomib, carfilzomib and ixazomib. These inhibitors, especially bortezomib, suffer from poor specificity and relatively high prevalence of resistance, therefore new inhibitors should be designed such that these characteristics improve. This thesis details probing of the relatively unexplored primed site binding channel of the β5 subunit of the proteasome with P2 extended proteasome inhibitors. This work indicates the primed site binding channel as a promiscuous target for interaction which may aid in increasing the specificity of proteasome inhibitors Chapter 1 introduces the structure and activity of the proteasome and its implications and relevance to human diseases. Inhibition of the proteasome by small molecule inhibitors is discussed, including the main classes, exemplary inhibitors, their mechanisms and applications. The primed site binding channel is then identified via examination of the crystal structure of the proteasome as a pocket which provides potential for new inhibitor-enzyme interactions. Chapter 2 details the design, synthesis and evaluation of inhibitors 2.01-2.04 which probe the extent of the promiscuity of the primed site binding channel. The collection of published inhibitors which are known to, or are likely to, occupy the primed binding sites demonstrate the primed site binding channel as promiscuous regarding the substituents it accepts. The P2 residue of bortezomib was identified as providing an access point to the primed binding sites. Imidazolyl and phenyl substituents were demonstrated to be accommodated by the primed site binding channel, with greater potency found for longer extensions into the pocket, or inhibitors with a phenyl substituent within the pocket. Chapter 3 describes further probing of the primed site binding channel with the azobenzene-containing proteasome inhibitor 3.01, which can be converted between cis- and trans-enriched isomeric states using light. The azobenzene substituent was placed at the P2 position of a bortezomib-inspired inhibitor and allowed probing of the primed binding sites with greater conformation predictability. Remarkably, despite significant change in conformation between the cis and trans isomers, there is little difference between the low nanomolar range potencies of the isomeric states. This further indicates the significant promiscuity of the primed site binding channel. Chapter 4 presents the evaluation of inhibitors 2.01-2.04 and the thermally adapted state of 3.01 alongside bortezomib against bovine α-chymotrypsin to examine the specificity of such inhibitors. Primed site-occupying inhibitors 2.01 and 2.04 demonstrate more than 2.5 times greater specificity towards the β5 subunit of the proteasome over α-chymotrypsin. This result indicates occupying the primed site binding channel as an effective strategy of improving proteasome inhibitor specificity, which may be critical in improving upon the currently available proteasomeThesis (MPhil) -- University of Adelaide, School of Physical Sciences, 202