Instructing Normalcy

Senior Project submitted to The Division of Multidisciplinary Studies of Bard College

Configurationally stable, enantioenriched organometallic nucleophiles in stereospecific Pd-catalyzed cross-coupling reactions: an alternative approach to asymmetric synthesis

Several research groups have recently developed methods to employ configurationally stable, enantioenriched organometallic nucleophiles in stereospecific Pd-catalyzed cross-coupling reactions. By establishing the absolute configuration of a chiral alkyltin or alkylboron nucleophile prior to its use in cross-coupling reactions, new stereogenic centers may be rapidly and reliably generated with preservation of the known initial stereochemistry. While this area of research is still in its infancy, such stereospecific cross-coupling reactions may emerge as simple, general methods to access diverse, optically active products from common enantioenriched organometallic building blocks. This minireview highlights recent progress towards the development of general, stereospecific Pd-catalyzed crosscoupling reactions using configurationally stable organometallic nucleophiles

Angiogenesis Is Enhanced in Ischemic Canine Myocardium by Transmyocardial Laser Revascularization 11This study was supported in part by a research grant from CardioGenesis Corporation, Sunnyvale, California.

AbstractObjectives. This study sought to test whether transmyocardial laser revascularization (TMLR) stimulates angiogenesis in an animal model of chronic ischemia.Background. TMLR relieves angina and may also improve blood flow in patients who are not candidates for traditional therapies. The mechanisms of these benefits are not fully defined.Methods. Ischemia was created in 14 dogs by proximal left anterior descending coronary ameroid constrictors. TMLR was performed in the anterior wall (∼1 channel/cm2) of seven dogs; the remaining dogs served as the ischemic control group. Myocardial blood flow was measured (colored microspheres) at rest and during chemical stress (adenosine) in the acute setting and after 2 months.Results. TMLR did not influence blood flow in the acute setting. After 2 months, resting blood flow increased comparably in the anterior wall in both groups to ∼80% of normal. However, the TMLR-treated dogs demonstrated an ∼40% increase in blood flow capacity during stress in the ischemic territory compared with untreated dogs (left anterior descending coronary artery/left circumflex coronary artery flow 0.53 ± 0.16 in the control group vs. 0.73 ± 0.08 in TMLR animals, p < 0.05). Vascular proliferation, assessed by bromodeoxyuridine incorporation and proliferating cell nuclear antigen positivity in endothelial and smooth muscle cells was about four times greater in the TMLR group than in the control group (p < 0.001). The density of vessels with at least one smooth muscle cell layer was ∼1.4 times greater in the myocardium surrounding the TMLR channel remnants than in control ischemic tissue (p < 0.001).Conclusions. In this canine model of chronic ischemia, TMLR significantly enhances angiogenesis as evidenced by the increased number of vessels lined with smooth muscle cells, markedly increased vascular proliferation and increased blood flow capacity during stress

Morphology and Oxygen Sensor Response of Luminescent Ir-Labeled Poly(dimethylsiloxane)/Polystyrene Polymer Blend Films

Polymer films consisting of a linear poly(dimethylsiloxane) end-functionalized with a luminescent Ir(III) complex (Ir−PDMS), blended with polystyrene (PS), function as optical oxygen sensors. The sensor response arises by quenching of the luminescence from the Ir(III) chromophore by oxygen that permeates into the polymer film. The morphology and luminescence oxygen sensor properties of blend films consisting of Ir−PDMS and PS have been characterized by fluorescence microscopy, atomic force microscopy, and scanning electron microscopy. The investigations demonstrate that microscale phase segregation occurs in the films. In blends that contain a relatively small amount of Ir−PDMS in PS (ca. 10 wt %), the Ir−PDMS exists as circular domains, with diameters ranging from 2 to 5 μm, surrounded by the majority PS phase. For larger weight fractions of Ir−PDMS in the blends, the film morphology becomes bicontinuous. A novel epifluorescence microscopy method is applied that allows the construction of Stern−Volmer quenching images that quantify the oxygen sensor response of the blend films with micrometer spatial resolution. These images provide a map of the oxygen permeability of the polymer blend films with a spatial resolution of ca. 1 μm. The results of this investigation show that the micrometer-sized Ir−PMDS domains display a 2−3-fold higher oxygen sensor response compared to the surrounding PS matrix. This result is consistent with the fact that PDMS is considerably more gas permeable compared to PS. The relationship of the microscale morphology of the blends to their performance as macroscale optical oxygen sensors is discussed

Identification and visualization of multidimensional antigen-specific T-cell populations in polychromatic cytometry data.

An important aspect of immune monitoring for vaccine development, clinical trials, and research is the detection, measurement, and comparison of antigen-specific T-cells from subject samples under different conditions. Antigen-specific T-cells compose a very small fraction of total T-cells. Developments in cytometry technology over the past five years have enabled the measurement of single-cells in a multivariate and high-throughput manner. This growth in both dimensionality and quantity of data continues to pose a challenge for effective identification and visualization of rare cell subsets, such as antigen-specific T-cells. Dimension reduction and feature extraction play pivotal role in both identifying and visualizing cell populations of interest in large, multi-dimensional cytometry datasets. However, the automated identification and visualization of rare, high-dimensional cell subsets remains challenging. Here we demonstrate how a systematic and integrated approach combining targeted feature extraction with dimension reduction can be used to identify and visualize biological differences in rare, antigen-specific cell populations. By using OpenCyto to perform semi-automated gating and features extraction of flow cytometry data, followed by dimensionality reduction with t-SNE we are able to identify polyfunctional subpopulations of antigen-specific T-cells and visualize treatment-specific differences between them

Evidence for Steady Heating: Observations of an Active Region Core with Hinode and TRACE

Previous observations have not been able to exclude the possibility that high temperature active region loops are actually composed of many small scale threads that are in various stages of heating and cooling and only appear to be in equilibrium. With new observations from the EUV Imaging Spectrometer (EIS) and X-ray Telescope (XRT) on \textit{Hinode} we have the ability to investigate the properties of high temperature coronal plasma in extraordinary detail. We examine the emission in the core of an active region and find three independent lines of evidence for steady heating. We find that the emission observed in XRT is generally steady for hours, with a fluctuation level of approximately 15% in an individual pixel. Short-lived impulsive heating events are observed, but they appear to be unrelated to the steady emission that dominates the active region. Furthermore, we find no evidence for warm emission that is spatially correlated with the hot emission, as would be expected if the high temperature loops are the result of impulsive heating. Finally, we also find that intensities in the "moss", the footpoints of high temperature loops, are consistent with steady heating models provided that we account for the local expansion of the loop from the base of the transition region to the corona. In combination, these results provide strong evidence that the heating in the core of an active region is effectively steady, that is, the time between heating events is short relative to the relevant radiative and conductive cooling times.Comment: Minor changes based on the final report from the referee; Movies are available from the first autho

Effects of combination of sibutramine and L-carnitine compared with sibutramine monotherapy on inflammatory parameters in diabetic patients

The aim of the study was to evaluate the effects of 12-month treatment with sibutramine plus L-carnitine compared with sibutramine alone on body weight, glycemic control, insulin resistance, and inflammatory state in type 2 diabetes mellitus patients. Two hundred fifty-four patients with uncontrolled type 2 diabetes mellitus (glycated hemoglobin [HbA(1c)] >8.0\%) in therapy with different oral hypoglycemic agents or insulin were enrolled in this study and randomized to take sibutramine 10 mg plus L-carnitine 2 g or sibutramine 10 mg in monotherapy. We evaluated at baseline and after 3, 6, 9, and 12 months these parameters: body weight, body mass index, HbA(1c), fasting plasma glucose, postprandial plasma glucose, fasting plasma insulin, homeostasis model assessment of insulin resistance index, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, leptin, tumor necrosis factor-α, adiponectin, vaspin, and high-sensitivity C-reactive protein. Sibutramine plus L-carnitine gave a faster improvement of fasting plasma glucose, postprandial plasma glucose, lipid profile, leptin, tumor necrosis factor-α, and high-sensitivity C-reactive protein compared with sibutramine alone. Furthermore, there was a better improvement of body weight, HbA(1c), fasting plasma insulin, homeostasis model assessment of insulin resistance index, vaspin, and adiponectin with sibutramine plus L-carnitine compared with sibutramine alone. Sibutramine plus L-carnitine gave a better and faster improvement of all the analyzed parameters compared with sibutramine alone without giving any severe adverse effect