Cinq Etudes-Tableaux by Serge Rachmaninoff orchestrated by Ottorino Respighi: A *transcription for wind orchestra with accompanying historical context and transcription techniques

This document includes a transcription of three of the five movements of Ottorino Respighi\u27s transcription of Serge Rachmaninoff\u27s piano work Cinq Etudes-Tableaux. An overview of the historical context of the work, and a detailed explanation of the techniques used in transcribing the work for wind orchestra are included. The three movements transcribed in this document are: 2. La Foire; 4. Marche Funebre; and 5. Marche

Reaction of Boron Trichloride with Methoxyamine Hydrochloride

Boron trichloride and methoxyamine hydrochloride were reacted in refluxing chlorobenzene and again in a refluxing mixture of chlorobenzene and chloroform. Procedures for handling and analyzing samples under anhydrous conditions are discussed. Evidence is given for the formation of B-trichloro-N-trimethoxyborazine in the chlorobenzene/chloroform system

The role of perlecan and endorepellin in the control of tumor angiogenesis and endothelial cell autophagy.

During tumor growth and angiogenesis there is a dynamic remodeling of tissue architecture often accompanied by the release of extracellular matrix constituents full of biological activity. One of the key constituents of the tumor microenvironment is the large heparan sulfate proteoglycan perlecan. This proteoglycan, strategically located at cell surfaces and within basement membranes, is a well-defined pro-angiogenic molecule when intact. However, when partially processed by proteases released during cancer remodeling and invasion, the C-terminal fragment of perlecan, known as endorepellin, has opposite effects than its parent molecule. Endorepellin is a potent inhibitor of angiogenesis by exerting a dual receptor antagonism by simultaneously engaging VEGFR2 and α2β1 integrin. Signaling through the α2β1 integrin leads to actin disassembly and block of endothelial cell migration, necessary for capillary morphogenesis. Signaling through the VEGFR2 induces dephosphorylation of the receptor via activation of SHP-1 and suppression of downstream proangiogenic effectors, especially attenuating VEGFA expression. A novel and emerging role of endorepellin is its ability to evoke autophagy by activating Peg3 and various canonical autophagic markers. This effect is specific for endothelial cells as these are the primary cells expressing both VEGFR2 and α2β1 integrin. Thus, an endogenous fragment of a ubiquitous proteoglycan can regulate both angiogenesis and autophagy through a dual receptor antagonism. The biological properties of this natural endogenous protein place endorepellin as a potential therapeutic agent against cancer or diseases where angiogenesis is prominent

The roles of FOXP3 and CXCR4 in breast cancer

PhD ThesisThe X-chromosome linked transcription factor, FOXP3, is expressed by epithelial cells from several organs. In these cells it is considered a potent tumour suppressor directly regulating the expression of many important oncogenes. The chemokine receptor, CXCR4, can also direct a number of processes relevant to the development of breast cancer. These include chemotaxis towards the sole ligand for CXCR4, CXCL12, which is expressed at the most common sites of metastatic spread. This study was designed to define further the role FOXP3 plays in metastatic breast cancer, with a particular focus on its potential to regulate CXCR4. In comparison with normal primary breast epithelial cells, FOXP3 was downregulated at both transcript and protein levels in the breast cancer cell lines, MCF-7 and MDA-MB-231. In the more invasive MDA-MB-231, the remaining FOXP3 was located predominately within the cytoplasm and lacked the natural Δ3 isoform. Following stable FOXP3 overexpression in MDA-MB-231, significant decreases were observed in the expression of ErbB2, SKP2, c-MYC and CXCR4. In contrast, an increase in p21 expression led to inhibition of cell proliferation, with a greater proportion in the G1 phase of the cell cycle suggesting the induction of senescence. Specific knockdown of FOXP3 in normal breast epithelial cells with siRNA significantly increased ErbB2, SKP2, c-MYC and CXCR4, and decreased p21 expression. These cells also showed a significantly increased chemotactic response towards CXCL12, suggesting a role for FOXP3 influencing cell migration. The expression of FOXP3 and CXCR4 in normal breast tissue (n=2), and both lymph node negative (n=7) and lymph node positive (n=9) breast cancer samples was investigated by immunohistochemistry. Both epithelial and cancer cells in all the breast cancer samples showed increased CXCR4 expression in comparison to normal tissue. However, the expression of FOXP3 by epithelial or cancer cells did not appear different between all the samples examined. Results from this study are consistent with FOXP3 functioning as an important tumour suppressor in breast cancer. Indeed, the functions of FOXP3 in breast epithelium can now potentially be extended to include influencing the expression of CXCR4 and response to the pro-metastatic chemokine, CXCL12. Further studies should be directed to investigation of the molecular mechanisms involved in this influence of chemokine responsiveness by FOXP3

Role of Platelet-Activating Factor and Hypoxia in Persistent Pulmonary Hypertension of the Newborn — Studies with Perinatal Pulmonary Vascular Smooth Muscle Cells

Platelet-activating factor (PAF) plays an important physiological role of maintaining a high vasomotor tone in fetal pulmonary circulation. At birth, endogenous vasodilators such as nitric oxide and prostacyclin are released and facilitate pulmonary vasodilation via cAMP-dependent protein kinase (cAMP/PKA) and cGMP-dependent protein kinase (cGMP/PKG) pathways. Interaction between the cyclic nucleotides and PAF receptor (PAFR)-mediated responses in pulmonary arterial smooth muscle is not well understood. To further understand the interactions of PAF-PAFR pathway and the cyclic nucleotides in ovine fetal pulmonary arterial smooth muscle cells (FPASMC), effects of cAMP and cGMP on PAFR-mediated responses in pulmonary arterial smooth muscle cells (PASMC) were studied. Ovine FPASMC were incubated with 10μM cAMP or cGMP in normoxia (5% CO2 in air, pO2~100 Torr) or hypoxia (2% O2, 5% CO2, pO2~30-40 Torr). Proteins were prepared and subjected to Western blotting. Effect of cell permeable cAMP and cGMP on PAFR binding was also studied and effect of cAMP on cell proliferation was also studied by RNAi to PKA-Cα. cAMP and cGMP significantly decreased PAFR binding and protein expression in normoxia and hypoxia, more so in hypoxia, when PAFR expression was usually high. PKA-Cα siRNA demonstrated that inhibition of PAFR-mediated responses by the cyclic nucleotides occurred through PKA. These data suggest that the normally high levels of cyclic nucleotides in the normoxic newborn pulmonary circulation assist in the downregulation of postnatal PAFR-mediated responses and that under hypoxic conditions, increasing the levels of cyclic nucleotides will abrogate PAF-mediated vasoconstriction thereby ameliorating PAF-induced persistent pulmonary hypertension of the newborn

Lethal Injection, Politics, and the Future of the Death Penalty

“Welcome and Keynote:” Stephen Bright, Harvey Karp Visiting Lecturer at Yale Law School, and President and Senior Counsel with the Southern Center for Human Rights. (9:00 a.m. - 9:45 a.m.) “The Death Penalty Today: Lethal Injection Issues:” Panel 1 featured Deborah W. Denno, Arthur A. McGivney Professor of Law at Fordham University School of Law; Joel Zivot, Assistant Professor of Anesthesiology and Surgery at Emory University School of Medicine, and Medical Director of the Cardiothoracic Intensive Care Unit at Emory University Hospital; Eric Berger, Associate Professor of Law at Nebraska College of Law; and Frank Green, Reporter for the Richmond Times-Dispatch. Jim Gibson, Associate Dean for Student Affairs and Professor of Law at the University of Richmond School of Law, served as moderator. (10:00 a.m. -11:30 a.m.) “The Shifting Politics of the Death Penalty:” Panel 2 featured Mark Earley, former Attorney General of Virginia; Richard B. Roper, Partner with Thompson & Knight LLP, Corinna Barrett Lain, Associate Dean for Faculty Development and Professor of Law at the University of Richmond School of Law; and Stephen Smith, Professor of Law at Notre Dame Law School. Henry L. Chambers, Professor of Law at the University of Richmond School of Law, served as moderator. (1:00 p.m. - 2:30 p.m.) “The Future of the Death Penalty:” Panel 3 featured John Douglass, Professor of Law at the University of Richmond School of Law; Brandon L. Garrett, Professor of Law at the University of Virginia School of Law; and Richard Dieter, Executive Director of the Death Penalty Information Center. Mary Kelly Tate, Professor of Law at the University of Richmond School of Law, served as moderator. (2:45 p.m. - 4:15 p.m.

A DedA Family Membrane Protein Is Required for Burkholderia thailandensis Colistin Resistance

© Copyright © 2019 Panta, Kumar, Stafford, Billiot, Douglass, Herrera, Trent and Doerrler. Colistin is a “last resort” antibiotic for treatment of infections caused by some multidrug resistant Gram-negative bacterial pathogens. Resistance to colistin varies between bacterial species. Some Gram-negative bacteria such as Burkholderia spp. are intrinsically resistant to very high levels of colistin with minimal inhibitory concentrations (MIC) often above 0.5 mg/ml. We have previously shown DedA family proteins YqjA and YghB are conserved membrane transporters required for alkaline tolerance and resistance to several classes of dyes and antibiotics in Escherichia coli. Here, we show that a DedA family protein in Burkholderia thailandensis (DbcA; DedA of Burkholderia required for colistin resistance) is a membrane transporter required for resistance to colistin. Mutation of dbcA results in \u3e100-fold greater sensitivity to colistin. Colistin resistance is often conferred via covalent modification of lipopolysaccharide (LPS) lipid A. Mass spectrometry of lipid A of ΔdbcA showed a sharp reduction of aminoarabinose in lipid A compared to wild type. Complementation of colistin sensitivity of B. thailandensis ΔdbcA was observed by expression of dbcA, E. coli yghB or E. coli yqjA. Many proton-dependent transporters possess charged amino acids in transmembrane domains that take part in the transport mechanism and are essential for function. Site directed mutagenesis of conserved and predicted membrane embedded charged amino acids suggest that DbcA functions as a proton-dependent transporter. Direct measurement of membrane potential shows that B. thailandensis ΔdbcA is partially depolarized suggesting that loss of protonmotive force can lead to alterations in LPS structure and severe colistin sensitivity in this species