Dictators, Fry Cooks, Film Students, Basketball Players, and Gang Bangers: How Shakespeare Looks on Film in the Late Twentieth Century and Beyond

Within the genre of the alternative Shakespearean universe, there exist two sub-genres. The two sub-genres are the Shakespeare language, contemporary era film and the contemporary language, contemporary era. Though films in these genres have existed since the dawn of filmmaking, they recently been marketed to more mainstream audiences. This thesis incorporates five ofthe more recent examples of these particular genres of Shakespearean film: William Shakespeare\u27s Romeo + Juliet, Hamlet, Richard III, 0, and Scotland, Pa. Each film is a unique take on the original Shakespearean work that it represents. The filmmakers include many of their own original ideas along with a re-imagining of the ideas taken directly from Shakespeare. In many cases the filmmakers have decided to tailor events and character motivations to fit the film that they have chosen to create. The choices, and their degree of success, must be analyzed in order to provide a complete analysis of the films. Many scholars and critics have viewed these films harshly upon their release and·again when subjected to critical study. This is not entirely fair, as the films cannot be judged based on their faithfulness to the original work alone. The audience has changed since the time in which Shakespeare lived and, as a result, some of the stories need to be changed as well

Rational Design of Transparent Nanowire Architectures with Tunable Geometries for Preventing Marine Fouling

Marine biofouling is a sticky global problem that hinders maritime industries. Various microscale surface structures inspired by marine biological species have been explored for their anti- fouling properties. However, systematic studies of anti- marine- fouling performance on surface architectures with characteristic length- scales spanning from below 100 nm to greater than 10 µm are generally lacking. Herein, a study on the rational design and fabrication of ZnO/Al2O3 core- shell nanowire architectures with tunable geometries (length, spacing, and branching) and surface chemistry is presented. The ability of the nanowires to significantly delay or prevent marine biofouling is demonstrated. Compared to planar surfaces, hydrophilic nanowires can reduce fouling coverage by up to - 60% after 20 days. The fouling reduction mechanism is mainly due to two geometric effects: reduced effective settlement area and mechanical cell penetration. Additionally, superhydrophobic nanowires can completely prevent marine biofouling for up to 22 days. The nanowire surfaces are transparent across the visible spectrum, making them applicable to windows and oceanographic sensors. Through the rational control of surface nano- architectures, the coupled relationships between wettability, transparency, and anti- biofouling performance are identified. It is envisioned that the insights gained from the work can be used to systematically design surfaces that reduce marine biofouling in various industrial settings.Core- shell nanowire architectures with tunable geometries (length, spacing, and branching) and surface chemistry are shown to significantly delay marine biofouling. The fouling reduction mechanism is mainly due to the two effects: reduced effective settlement area and mechanical biocide. The insights gained from the work can be used to systematically design surfaces that reduce marine biofouling in various industrial settings.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/162819/3/admi202000672-sup-0001-SuppMat.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162819/2/admi202000672_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162819/1/admi202000672.pd

TCF7L2 single nucleotide polymorphisms, cardiovascular disease and all-cause mortality: the Atherosclerosis Risk in Communities (ARIC) study

We hypothesize that transcription factor 7-like 2 (TCF7L2) single nucleotide polymorphisms (SNPs) are associated with cardiovascular disease (CVD) and that the associations differ in diabetic and non-diabetic participants

Variation in TCF7L2 and Increased Risk of Colon Cancer: The Atherosclerosis Risk in Communities (ARIC) Study

To determine whether variation in the transcription factor 7-like 2 (TCF7L2) gene, which influences diabetes risk, is associated with incidence of cancers

Association of a Fasting Glucose Genetic Risk Score With Subclinical Atherosclerosis: The Atherosclerosis Risk in Communities (ARIC) Study

Elevated fasting glucose level is associated with increased carotid intima-media thickness (IMT), a measure of subclinical atherosclerosis. It is unclear if this association is causal. Using the principle of Mendelian randomization, we sought to explore the causal association between circulating glucose and IMT by examining the association of a genetic risk score with IMT. The sample was drawn from the Atherosclerosis Risk in Communities (ARIC) study and included 7,260 nondiabetic Caucasian individuals with IMT measurements and relevant genotyping. Components of the fasting glucose genetic risk score (FGGRS) were selected from a fasting glucose genome-wide association study in ARIC. The score was created by combining five single nucleotide polymorphisms (SNPs) (rs780094 [GCKR], rs560887 [G6PC2], rs4607517 [GCK], rs13266634 [SLC30A8], and rs10830963 [MTNR1B]) and weighting each SNP by its strength of association with fasting glucose. IMT was measured through bilateral carotid ultrasound. Mean IMT was regressed on the FGGRS and on the component SNPs, individually. The FGGRS was significantly associated (P = 0.009) with mean IMT. The difference in IMT predicted by a 1 SD increment in the FGGRS (0.0048 mm) was not clinically relevant but was larger than would have been predicted based on observed associations between the FFGRS, fasting glucose, and IMT. Additional adjustment for baseline measured glucose in regression models attenuated the association by about one third. The significant association of the FGGRS with IMT suggests a possible causal association of elevated fasting glucose with atherosclerosis, although it may be that these loci influence IMT through nonglucose pathways

Genetic variants in TLR2 and TLR4 are associated with markers of monocyte activation: the Atherosclerosis Risk in Communities MRI Study

Markers of monocyte activation play a critical role in atherosclerosis, but little is known about the genetic influences on cellular levels. Therefore, we investigated the influence of genetic variants in monocyte differentiation antigen (CD14), toll-like receptor-4 (TLR4), toll-like receptor-2 (TLR2), and myeloperoxidase (MPO) on monocyte surface receptor levels. The study sample consisted of 1,817 members of a biracial cohort of adults from the Atherosclerosis Risk in Communities Carotid MRI Study. Monocyte receptors were measured using flow cytometry on fasting whole blood samples. TLR2 rs1816702 genotype was significantly associated with CD14+/TLR2+ percent of positive cells (%) and median fluorescence intensity (MFI) in whites but not in blacks (p < 0.001). Specifically, the presence of the minor T-allele was associated with increased receptor levels. In blacks, TLR4 rs5030719 was significantly associated with CD14+/TLR4+ monocytes (MFI) with mean ± SE intensities of 16.7 ± 0.05 and 16.0 ± 0.14 for GG and GT/TT genotypes, respectively (p < 0.001). Variants in TLR2 and TLR4 were associated with monocyte receptor levels of TLR2 and TLR4, respectively, in a biracial cohort of adults. To our knowledge, this is the first study to look at associations between variants in the toll-like receptor family and toll-like receptor levels on monocytes

Polymorphisms in the ICAM1 gene predict circulating soluble intercellular adhesion molecule-1(sICAM-1)

Polymorphisms within the ICAM1 structural gene have been shown to influence circulating levels of soluble intercellular adhesion molecule -1 (sICAM-1) but their relation to atherosclerosis has not been clearly established. We sought to determine whether ICAM1 SNPs are associated with circulating sICAM-1 concentration, coronary artery calcium (CAC), and common and internal carotid intima medial thickness (IMT)

Does prior acute exercise affect postexercise substrate oxidation in response to a high carbohydrate meal?

<p>Abstract</p> <p>Background</p> <p>Consumption of a mixed meal increases postprandial carbohydrate utilization and decreases fat oxidation. On the other hand, acute endurance exercise increases fat oxidation and decreases carbohydrate utilization during the post-exercise recovery period. It is possible that the resulting post-exercise increase in circulating nonesterified fatty acids could attenuate the ability of ingested carbohydrate to inhibit lipid oxidation. The purpose of this study was to determine whether prior exercise attenuates the usual meal-induced decline in lipid oxidation.</p> <p>Methods</p> <p>Six healthy, physically active young subjects (x age = 26.3 years, 4 males, 2 females) completed three treatments in random order after a ~10 h fast: (a) Exercise/Carbohydrate (Ex/CHO) – subjects completed a bout of exercise at 70% VO_2peak(targeted net energy cost of 400 kcals), followed by consumption of a carbohydrate-rich meal; (b) Exercise/Placebo (Ex/Placebo) – subjects completed an identical bout of exercise followed by consumption of a placebo; and (c) No Exercise/Carbohydrate (NoEx/CHO) – subjects sat quietly rather than exercising and then consumed the carbohydrate-rich meal. Blood samples were obtained before and during the postprandial period to determine plasma glucose, insulin, and non-esterified fatty acids (NEFA). Respiratory gas exchange measures were used to estimate rates of fat and carbohydrate oxidation.</p> <p>Results</p> <p>Plasma NEFA were approximately two-fold higher immediately following the two exercise conditions compared to the no-exercise condition, while meal consumption significantly increased insulin and glucose in both Ex/CHO and NoEx/CHO. NEFA concentrations fell rapidly during the 2-h postprandial period, but remained higher compared to the NoEx/CHO treatment. Carbohydrate oxidation increased rapidly and fat oxidation decreased in response to the meal, with no differences in the rates of carbohydrate and fat oxidation during recovery between the Ex/CHO and NoEx/CHO conditions.</p> <p>Conclusion</p> <p>The plasma NEFA concentration is increased during the post exercise period, which is associated with elevated fat oxidation when no meal is consumed. However, when a mixed meal is consumed immediately following exercise, the initially elevated plasma NEFA concentration decreases rapidly, and postexercise fat oxidation during this 2-h postexercise, postprandial period is no higher than that of the 2-h postprandial period without prior exercise.</p

Cell-active small molecule inhibitors validate the SNM1A DNA repair nuclease as a cancer target

The three human SNM1 metallo-β-lactamase fold nucleases (SNM1A–C) play key roles in DNA damage repair and in maintaining telomere integrity. Genetic studies indicate that they are attractive targets for cancer treatment and to potentiate chemo- and radiation-therapy. A high-throughput screen for SNM1A inhibitors identified diverse pharmacophores, some of which were shown by crystallography to coordinate to the di-metal ion centre at the SNM1A active site. Structure and turnover assay-guided optimization enabled the identification of potent quinazoline–hydroxamic acid containing inhibitors, which bind in a manner where the hydroxamic acid displaces the hydrolytic water and the quinazoline ring occupies a substrate nucleobase binding site. Cellular assays reveal that SNM1A inhibitors cause sensitisation to, and defects in the resolution of, cisplatin-induced DNA damage, validating the tractability of MBL fold nucleases as cancer drug targets

Association of Toll-like receptor 4 (TLR4) with chronic plaque type psoriasis and psoriatic arthritis.

Family studies have provided overwhelming evidence for an underlying genetic component to psoriasis. Toll-like receptors (TLRs) are key transmembrane proteins in both the innate and adaptive immune responses which are known to be integral processes in psoriasis. Recent functional studies support this notion having suggested a role for TLR4 in the pathogenesis of psoriasis. Furthermore a missense polymorphism in the TLR4 gene has been associated with a number of autoimmune conditions, including Crohn diseases, making TLR4 a viable candidate gene for investigation. The aim of this study was to investigate polymorphisms across the TLR4 region with a high-density single nucleotide polymorphism (SNP) panel in a large cohort of patients with chronic plaque type psoriasis. Twenty SNPs were successfully genotyped using Sequenom iPLEX Gold platform in 2826 UK chronic plaque type psoriasis patients including subgroup data on presence of confirmed psoriatic arthritis (n = 1839) and early-onset psoriasis (n = 1466) was available. Allele frequencies for psoriasis patients were compared against imputed Wellcome Trust Case Control Consortium controls (n = 4861). Significant association was observed between a missense variant rs4986790 of TLR4 (Asp229Gly) and plaque type psoriasis (p = 2 × 10(-4)) which was also notable in those with psoriatic arthritis (p = 2 × 10(-4)) and early-onset psoriasis (p = 8 × 10(-4)). We present data suggestive of an association between a functional variant and an intronic variant of TLR4 and chronic plaque type psoriasis and psoriatic arthritis. However, validation of this association in independent cohorts will be necessary