Samuel Taylor Coleridge and Opium.

Coleridge\u27s usual use of opium was through laudanum, a mixture of opium and alcohol. This thesis presents the history of and criticism regarding the poet\u27s use of laudanum and the physical and emotional consequences the drug held for him and his writing career

Correlations between Activity and Blood Pressure in African American Women and Girls

Is the level of physical activity recommended by the Surgeon General enough to elicit the beneficial effects of exercise on blood pressure in African American women and girls? This study investigated self-reported physical activity level and its relationship to blood pressure in a population of African American women (N=25) between the ages of 21 and 53 years and girls (N=52) between the ages of 5 and 17 years, in Dayton, Ohio, USA. Physical activity levels were estimated by an interviewer-administered questionnaire, which determined the average hours per week over the past year spent in occupational and leisure activities. Blood pressure was also measured. 56% of the women had average physical activity levels of 3.7 MET-hours per week, and 73% of the girls had average physical activity levels of 3.9 MET-hours per week compared to the Surgeon General’s recommendation of 7.5-15 MET-hours per week. Inverse correlations between self-reported physical activity level and systolic and diastolic blood pressures were statistically significant in some but not all of the groups. These data suggest that increasing physical activity levels should be considered as part of an intervention program for African American women to control systolic and diastolic blood pressures

Intercellular Interactions in PC12 Cells Overexpressing Beta/A4 Amyloid

The amyloid precursor protein (APP) is an integral membrane component of eukaryotic cells. A variety of research approaches have addressed the contribution of the β amyloid peptide region of the APP to neuritic plaque structure and formation in the Alzheimer disease brain as well as the relationship between β amyloid accumulation and the occurrence of dementia. However, there is limited information available concerning the cellular consequences of amyloid deposition. The present studies were undertaken to investigate the relationship between β amyloid and intercellular junctions. Transfected PC12 cell lines, that overexpress the β amyloid peptide, exhibit structural and functional alterations at the cell surface and tend to form aggregates more readily than normal control cells. Intermediate junctions were the most common intercellular interactions of both normal and transfected cells. However, the control and transfected cells differed since areas of continuous and extensive junctions were readily seen in transfected cells and infrequently seen in control cells. The data suggest that excess accumulation of β amyloid is associated with the junctional apparatus and may be related to increased intercellular adhesion

Direct Light-Enabled Access to α-Boryl Radicals: Application in the Stereodivergent Synthesis of Allyl Boronic Esters

Operationally simple strategies to assemble boron containing organic frameworks are highly enabling in organic synthesis. While conventional retrosynthetic logic has engendered many platforms focusing on the direct formation of C−B bonds, α-boryl radicals have recently reemerged as versatile open-shell alternatives to access organoborons via adjacent C−C bond formation. Direct light-enabled α-activation is currently contingent on photo- or transition metal-catalysis activation to efficiently generate radical species. Here, we disclose a facile activation of α-halo boronic esters using only visible light and a simple Lewis base to enable homolytic scission. Intermolecular addition to styrenes facilitates the rapid construction of highly versatile E-allylic boronic esters. The simplicity of activation permits the strategic merger of this construct with selective energy transfer catalysis to enable the complimentary stereodivergent synthesis of Z-allylic boronic esters

Neuroimaging of Vessel Amyloid in Alzheimer's Disease a , b

Despite extensive recent advances in understanding Alzheimer's disease (AD) we are unable to noninvasively establish a definite diagnosis during life and cannot monitor the cerebral deposition of amyloid Β protein (A/Β) in living patients. We evaluated the use of 10H3, a monoclonal antibody Fab targeting AΒ protein 1-28 labeled with Tc-99m. Six subjects with probable AD were studied using single-photon emission computed tomography (SPECT) at times from 0–24 hours following injection. Curves of radioactivity in blood demonstrate a half-life of the injected Fab of 2–3 hours. Images show uptake around the head in the scalp or bone marrow in all subjects. There is no evidence of cerebral uptake of the antibody. Scalp biopsies in all six patients demonstrate diffuse staining with 10H3 of the scalp, a pattern indistinguishable from that found in controls. Evidence of amyloid deposition in the scalp in AD is not seen with other anti-AΒ antibodies, suggesting that 10H3 is cross-reacting with another protein. Further studies with anti-AΒ antibodies will require longer-lived radionuclides to detect cerebral uptake at later tunes after injection to allow for complete clearance from the blood. Afternately, imaging using labeled AΒ itself may provide a means for noninvasive targeting of cerebral amyloid.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73674/1/j.1749-6632.1997.tb48475.x.pd

Focused ultrasound to diagnose HIV-associated tuberculosis (FASH) in the extremely resource-limited setting of South Sudan: a cross-sectional study

Our cross-sectional study aimed at evaluating the diagnostic performance of Focused Assessment with Sonography for HIV-associated tuberculosis (FASH) to detect extrapulmonary tuberculosis in extremely resource-limited settings, with visceral leishmaniasis as a differential diagnosis with overlapping sonographic feature

Evaluation of heat transfer at the cavity-polymer interface in microinjection moulding based on experimental and simulation study

YesIn polymer melt processing, the heat transfer coefficient (HTC) determines the heat flux across the interface of the polymer melt and the mould wall. The HTC is a dominant parameter in cooling simulations especially for microinjection moulding, where the high surface to volume ratio of the part results in very rapid cooling. Moreover, the cooling rate can have a significant influence on internal structure, morphology and resulting physical properties. HTC values are therefore important and yet are not well quantified. To measure HTC in micromoulding, we have developed an experimental setup consisting of a special mould, and an ultra-high speed thermal camera in combination with a range of windows. The windows were laser machined on their inside surfaces to produce a range of surface topographies. Cooling curves were obtained for two materials at different processing conditions, the processing variables explored being melt and mould temperature, injection speed, packing pressure and surface topography. The finite element package Moldflow was used to simulate the experiments and to find the HTC values that best fitted the cooling curves, so that HTC is known as a function of the process variables explored. These results are presented and statistically analysed. An increase in HTC from the standard value of 2500 W/m2C to values in the region 7700 W/m2C was required to accurately model the observations.EPSR

Computational Protein Design to Re-Engineer Stromal Cell-Derived Factor-1α (SDF) Generates an Effective and Translatable Angiogenic Polypeptide Analog

BACKGROUND: Experimentally, exogenous administration of recombinant stromal cell-derived factor-1α (SDF) enhances neovasculogenesis and cardiac function after myocardial infarction. Smaller analogs of SDF may provide translational advantages including enhanced stability and function, ease of synthesis, lower cost, and potential modulated delivery via engineered biomaterials. In this study, computational protein design was used to create a more efficient evolution of the native SDF protein. METHODS AND RESULTS: Protein structure modeling was used to engineer an SDF polypeptide analog (engineered SDF analog [ESA]) that splices the N-terminus (activation and binding) and C-terminus (extracellular stabilization) with a diproline segment designed to limit the conformational flexibility of the peptide backbone and retain the relative orientation of these segments observed in the native structure of SDF. Endothelial progenitor cells (EPCs) in ESA gradient, assayed by Boyden chamber, showed significantly increased migration compared with both SDF and control gradients. EPC receptor activation was evaluated by quantification of phosphorylated AKT, and cells treated with ESA yielded significantly greater phosphorylated AKT levels than SDF and control cells. Angiogenic growth factor assays revealed a distinct increase in angiopoietin-1 expression in the ESA- and SDF-treated hearts. In addition, CD-1 mice (n=30) underwent ligation of the left anterior descending coronary artery and peri-infarct intramyocardial injection of ESA, SDF-1α, or saline. At 2 weeks, echocardiography demonstrated a significant gain in ejection fraction, cardiac output, stroke volume, and fractional area change in mice treated with ESA compared with controls. CONCLUSIONS: Compared with native SDF, a novel engineered SDF polypeptide analog (ESA) more efficiently induces EPC migration and improves post-myocardial infarction cardiac function and thus offers a more clinically translatable neovasculogenic therapy