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

Space-time segmentation method for study of the vertical structure and evolution of solar supergranulation from data provided by local helioseismology

Solar supergranulation remains a mystery in spite of decades of intensive studies. Most of the papers about supergranulation deal with its surface properties. Local helioseismology provides an opportunity to look below the surface and see the vertical structure of this convective structure. We present a concept of a (3+1)-D segmentation algorithm capable of recognising individual supergranules in a sequence of helioseismic 3-D flow maps. As an example, we applied this method to the state-of-the-art data and derived descriptive statistical properties of segmented supergranules -- typical size of 20--30 Mm, characteristic lifetime of 18.7 hours, and estimated depth of 15--20 Mm. We present preliminary results obtained on the topic of the three-dimensional structure and evolution of supergranulation. The method has a great potential in analysing the better data expected from the helioseismic inversions, which are being developed.Comment: 6 pages, 4 figures, accepted in New Astronom

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

Effects of telmisartan and ramipril on adiponectin and blood pressure in patients with type 2 diabetes

&lt;b&gt;Background:&lt;/b&gt; Adiponectin is secreted by adipose tissue and may play a role in cardiovascular disease. We examined adiponectin levels in patients with type 2 diabetes who participated in the Telmisartan vs. Ramipril in Renal Endothelial Dysfunction (TRENDY) study. &lt;b&gt;Methods&lt;/b&gt; A total of 87 patients were assessed at baseline and following 9 weeks treatment with the angiotensin-receptor blocker telmisartan (final dose, 80 mg; n = 45) or the angiotensin-converting enzyme inhibitor ramipril (final dose, 10 mg; n = 42). Adiponectin levels were measured in plasma by radioimmunoassay. &lt;b&gt;Results:&lt;/b&gt; Adiponectin levels were inversely correlated with systolic (SBP; r = -0.240, P &#60; 0.05) and diastolic (DBP; r = -0.227, P &#60; 0.05) blood pressure at baseline and following treatment with telmisartan or ramipril (SBP: r = -0.228, P &#60; 0.05; DBP: r = -0.286, P &#60; 0.05). Changes in adiponectin levels were related to changes in SBP (r = -0.357, P &#60; 0.01) and DBP (r = -0.286, P &#60; 0.01). There was a significant increase in adiponectin levels in the telmisartan (0.68 (95% confidence interval (CI), 0.27 to 1.10) &lt;sup&gt;&#181;&lt;/sup&gt;g/ml, P &#60; 0.01) but not in the ramipril group (0.17 (95% CI, -0.56 to 0.90) &lt;sup&gt;&#181;&lt;/sup&gt;g/ml, P = 0.67). Blood pressure reduction in the telmisartan group (DeltaSBP: -13.5 (95% CI, -17.0 to -10.0) mm Hg; &#916;DBP: -7.6 (95% CI, -9.8 to -5.3) mm Hg, each P &#60; 0.001) was significantly (P less than or equal to 0.01 for SBP and P &#60; 0.01 for DBP) greater than in the ramipril group (&#916;SBP: -6.1 (95% CI, -6.2 to -2.0) mm Hg; &#916;DBP: -2.7 (95% CI, -5.0 to -0.5) mm Hg; P &#60; 0.01 and P &#60; 0.05, respectively). &lt;b&gt;Conclusion:&lt;/b&gt; Adiponectin is correlated with blood pressure in patients with type 2 diabetes. Whether increased adiponectin contributes to the blood pressure–lowering effect of telmisartan needs further study

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