Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD.

Crystal structure of the sodium-proton antiporter NhaA dimer and new mechanistic insights

Sodium-proton antiporters rapidly exchange protons and sodium ions across the membrane to regulate intracellular pH, cell volume, and sodium concentration. How ion binding and release is coupled to the conformational changes associated with transport is not clear. Here, we report a crystal form of the prototypical sodium-proton antiporter NhaA from Escherichia coli in which the protein is seen as a dimer. In this new structure, we observe a salt bridge between an essential aspartic acid (Asp163) and a conserved lysine (Lys300). An equivalent salt bridge is present in the homologous transporter NapA, but not in the only other known crystal structure of NhaA, which provides the foundation of most existing structural models of electrogenic sodium-proton antiport. Molecular dynamics simulations show that the stability of the salt bridge is weakened by sodium ions binding to Asp164 and the neighboring Asp163. This suggests that the transport mechanism involves Asp163 switching between forming a salt bridge with Lys300 and interacting with the sodium ion. pKa calculations suggest that Asp163 is highly unlikely to be protonated when involved in the salt bridge. As it has been previously suggested that Asp163 is one of the two residues through which proton transport occurs, these results have clear implications to the current mechanistic models of sodium-proton antiport in NhaA.

Inter-observer agreement for diagnostic classification of esophageal motility disorders defined in high-resolution manometry

High-resolution esophageal manometry (HRM) is a recent development used in the evaluation of esophageal function. Our aim was to assess the inter-observer agreement for diagnosis of esophageal motility disorders using this technology. Practitioners registered on the HRM Working Group website were invited to review and classify (i) 147 individual water swallows and (ii) 40 diagnostic studies comprising 10 swallows using a drop-down menu that followed the Chicago Classification system. Data were presented using a standardized format with pressure contours without a summary of HRM metrics. The sequence of swallows was fixed for each user but randomized between users to avoid sequence bias. Participants were blinded to other entries. (i) Individual swallows were assessed by 18 practitioners (13 institutions). Consensus agreement (≤2/18 dissenters) was present for most cases of normal peristalsis and achalasia but not for cases of peristaltic dysmotility. (ii) Diagnostic studies were assessed by 36 practitioners (28 institutions). Overall inter-observer agreement was 'moderate' (kappa 0.51) being 'substantial' (kappa > 0.7) for achalasia type I/II and no lower than 'fair-moderate' (kappa >0.34) for any diagnosis. Overall agreement was somewhat higher among those that had performed >400 studies (n = 9; kappa 0.55) and 'substantial' among experts involved in development of the Chicago Classification system (n = 4; kappa 0.66). This prospective, randomized, and blinded study reports an acceptable level of inter-observer agreement for HRM diagnoses across the full spectrum of esophageal motility disorders for a large group of clinicians working in a range of medical institutions. Suboptimal agreement for diagnosis of peristaltic motility disorders highlights contribution of objective HRM metrics.

The independent role of prenatal and postnatal exposure to active and passive smoking on the development of early wheeze in children.

Maternal smoking during pregnancy increases childhood asthma risk, but health effects in children of nonsmoking mothers passively exposed to tobacco smoke during pregnancy are unclear. We examined the association of maternal passive smoking during pregnancy and wheeze in children aged ≤2 years.Individual data of 27 993 mother-child pairs from 15 European birth cohorts were combined in pooled analyses taking into consideration potential confounders.Children with maternal exposure to passive smoking during pregnancy and no other smoking exposure were more likely to develop wheeze up to the age of 2 years (OR 1.11, 95% CI 1.03-1.20) compared with unexposed children. Risk of wheeze was further increased by children's postnatal passive smoke exposure in addition to their mothers' passive exposure during pregnancy (OR 1.29, 95% CI 1.19-1.40) and highest in children with both sources of passive exposure and mothers who smoked actively during pregnancy (OR 1.73, 95% CI 1.59-1.88). Risk of wheeze associated with tobacco smoke exposure was higher in children with an allergic versus nonallergic family history.Maternal passive smoking exposure during pregnancy is an independent risk factor for wheeze in children up to the age of 2 years. Pregnant females should avoid active and passive exposure to tobacco smoke for the benefit of their children's health.

Janissaire-Tschausch-Fourier d'une oda en Habit de Cérémonies

Croqué d'apres Nature p. le B. de G. ; gravé p. J. C. Kilian

Na 1 Nachlass Max Horkheimer, 662 - "Research Project on Anti-Semitism" (p. IX 92.1b-IX 92.1d)

"International Institute of Social Research: Research-Project on Anti-Semitism" (1939-42) (veröffentlicht in Studies in Philosophy and Social Science Bd. IX, 1941, S. 124-143): 1. "Research Project on Anti-Semitism", b) Typoskript, 38 Blatt, c) Typoskript, 38 Blatt, d) Typoskript mit eigenhändigen und handschriftlichen Korrekturen, 46 Blatt;

Na 1 Nachlass Max Horkheimer, 669 - "Research Project on Anti-Semitism" u.a. (p. IX 121-IX 123)

American Jewish Committee: Meetings of the Advisory Council to Dr. Horkheimer, Sitzungsprotokolle Januar - April 1945, als Typoskripte vervielfältigt, 17 Blatt; Institute of Social Research: "Studies in Antisemitism. A Report on the cooperative project for the study of antisemitism for the year ending March 15, 1944, jointly sponsored by the American Jewish Committee and the Institute of Social Research" (August 1944), a) Typoskript, gebunden, 144 Blatt, b) Typoskript, 144 Blatt; "Report on the Scientific Department of the American Jewish Committee - Dr. Max Horkheimer, Chairman" (January 5, 1945) [1989 von: Hoover Institution, Stanford]: 1. Report, Typoskript (Kopie), 7 Blatt; 2. "Condensed Version of Report for Leidesdorf", Typoskript (Kopie) mit handschriftlichen Korrekturen, 2 Blatt; 3. Memorandum 5.12.1943, Typoskript (Kopie), 1 Blatt; "Meeting of Psychiatrists and Psychoanalysts for Consideration of a Research Project on the Psychology of Antisemitism" Protokoll des Trefffens am 19.4.1945, als Typoskript vervielfältigt, 7 Blatt; "Synopsis of a proposed article on Researches in Antisemitism" (1945): 1. Aufsatz-Entwurd, Typoskript, 8 Blatt, b) Typoskript, 6 Blatt, c) Typoskript, 7 Blatt, d) Typoskript mit handschriftlichen Korrekturen, 7 Blatt, e) Typoskript mit handschriftlichen Korrekturen, 6 Blatt, f) Typoskript mit handschriftlichen Korrekturen und Manuskript, 8 Blatt; 2. L. Sussman: Entwurf, 22.3.1945, Typoskript mit "handschriftlichen Korrekturen, 3 Blatt; 3. "Notes for Dr. Klein re: article in 'Harpers'", Typoskript, 1 Blatt; 4. Harper's Magazine: 1 Brief mit Unterschrift an Max Horkheimer, New York, 8.6.1945, 1 Brief von Max Horkheimer, ohne Ort, 22.5.1945, 2 Blatt;

Na 1 Nachlass Max Horkheimer, 687 - "Experimental Movie Project", "The Police and Minority Groups" u.a. (p. IX 150.1-17 - IX 152.1-2)

"Experimental Movie Project" (1945-46):; 1. "Below the Surface", Drehbuch des Testfilms, a) als Typoskript vervielfältigt, 46 Blatt, b) als Typoskript vervielfältigt, 26 Blatt, c) als Typoskript vervielfältigt, 26 Blatt, d) als Typoskript vervielfältigt, 26 Blatt "Experimental Movie Project" (1945-46): Memoranden zum Test; 2. 'Notes' 25.4.1946, Typoskript, 1 Blatt; 3. "Memorandum on Experimental Movie Project", 19.4.1946. Typoskript, 3 Blatt; 4. "Memorandum re: 'Below the Surface" (Juli 1945). Typoskript, 2 Blatt; 5. Dore Schary und Allen Rivkin: 'Memorandum, Subject: New Suggested Treatment for 'Below the Surface'", 13.7.1945. Typoskript, 2 Blatt; 6. Hans Richter: "Report about the film script 'Below the surface'", 7. u. 8.7.1945, a) Typoskript, 1 Blatt, b) Typoskript, 1 Blatt; 7. Hans Richter: Bestätigung der Vereinbarung mit dem American Jewish Committee, 3.7.1945. Typoskript, 1 Blatt; 8. "Notes and Suggestions re Experimental Motion Picture", Juni 1945. Typoskript, 2 Blatt; 9. Siegfried Kracauer; "Suggestions for the Dialogue" (4.4.1945). Typoskript, 3 Blatt; 10. "Motion Picture", März 1945. Typoskript, 5 Blatt; 11. "Project on a Test film", a) Typoskript, 4 Blatt, b) Typoskript, 5 Blatt; 12. "Memorandum re: 'Below the Surface'", a) Typoskript, 3 Blatt, b) Typoskript mit eigenhändigen Korrekturen von Theodor W. Adorno, 3 Blatt; "Experimental Movie Project" (1945-46): Korrespondenz zum Test-Film-Projekt:; 13. Friedrich Pollock: 1 Brief an Max Horkheimer, Santa Monica, California, 12.10.1945; 14. Theodor W. Adorno: 2 Briefe an Max Horkheimer, Los Angeles und Santa Monica, California, 1945; 15. Joseph M. Proskauer: 1 Brief von Max Horkheimer, o.O., 29.6.1945, 1 Brief mit Unterschrift an Max Horkheimer, o.O., o.D., 3 Blatt; 16. Alexander Hackenschmied, 1 Brief mit Unterschrift an Max Horkheimer, New York, 19.6.1945, 1 Blatt; 17. Gilbert Gabriel: 1 Brief von John Slawson, o.O., 22.3.1945, 2 Blatt; "The Police and Minority Groups" (1946):; 1. "The Police and Minority Groups". Typoskript, 2 Blatt; 2. Robert W. Kenny: "Police and Minority Groups - an Experiment". Als Typoskript vervielfältigt, 17 Blatt; 3. Davis McEntire, Robert B. Powers: "Police Training Bulletin. A Guide to Race Relations for Police Officers", State of California, 1946, 38 Seiten; Max Horkheimer: "Memorandum on a Study of Race Hatred in Post-War Germany" (1946):; 1. Memorandum, a) Typoskript, 8 Blatt, b) Typoskript mit eigenhändigen und handschriftlichen Korrekturen, 6 Blatt, c) Typoskript, 5 Blatt, d) Teilstück, Typoskript mit eigenhändigen Korrekturen, 1 Blatt e) Typoskript mit eigenhändigen Korrekturen, 5 Blatt, f) Teilstück, Typoskript mit handschriftlichen Korrekturen, 2 Blatt, g) Typoskript mit eigenhändigen Korrekturen, 7 Blatt, h) Teilstück, Typoskript mit eigenhändigen Korrekturen und Ergänzungen, 1 Blatt, i) Typoskript, 2 Blatt; 2. Theodor W. Adorno: "Ad Memorandum Neumann", Manuskript, 3 Blatt;

Na 1 Nachlass Max Horkheimer, 705 - Studien über Nationalismus und Autorität; Darmstädter Gemeindestudie; "Project on Attitudes of German Youth" u.a. (p. IX 176 - IX 181a)

"Gruppenuntersuchung über Nationalismus", Juni 1950. Typoskript mit handschriftlichen Ergänzungen von Friedrich Pollock, 18 Blatt; "Beitrag des Instituts für Sozialforschung zu dem Forschungsobjekt (Forschungsprojekt?) über Autorität", 1950/51, a) Typoskript, 5 Blatt, b) Typoskript mit dem Titel "New Project on Authority" mit handschriftlichen Korrekturen, 7 Blatt; "Memorandum über eine Studie zum Problem der Autorität im deutschen Erziehungswesen", ca. 1950. Typoskript, 4 Blatt; "Darmstädter Gemeindestudie", 1950-52: 1. Theodor W. Adorno: "Memorandum re: Stand der Darmstädter Gemeindestudie bei der Abreise von Theodor W. Adorno", 15.10.1952. Typoskript mit eigenhändigen Korrekturen, 2 Blatt; 2. Ansprache bei der Überreichung der ersten Publikationen der Studie an den Minister und den Bürgermeister von Darmstadt, 2.7.1952, Typoskript, 9 Blatt; 3. Max Horkheimer: "Gutachten über die Darmstädter Gemeindestudie", 1.4.1952. Typoskript, 2 Blatt; 4. "Memorandum on the Participation of the Institute of Social Research in the Darmstadt Community Study", 31.3.1952. Typoskript, 3 Blatt; 5. Theodor W. Adorno: 'Memorandum re: Darmstadt', 4.9.1951. Typoskript, 1 Blatt; 6. "Eine Untersuchung über die Einstellung der Arbeitnehmer zu ihren wirtschaftlichen Interessenvertretungen (Darmstädter Gemeindestudie). Entwurf", 20.7.1951. Typoskript mit handschriftlichen Korrekturen, 6 Blatt; 7. Theodor W. Adorno: "Memorandum über zwei an das Institut für Sozialforschung zu vergebende Aufträge im Rahmen der Darmstädter Gemeindestudie". Typoskripte, 6 Blatt; 8. Theodor W. Adorno: "Aktennotiz über die Besprechung am 20. November 1950 zwischen den Leitern der Darmstädter Gemeindestudie, insbesondere Dr. Grigsy und Magnifizenz Rolfes, und Theodor W. Adorno". Typoskript, 2 Blatt; 9. Bemerkungen zum Abbruch und zur Neuorganisation der Studie, für eine Rede in Chicago, Typoskript, englisch, ohne Datum, 1 Blatt; "Outline of a Study of In-Between-Culture" ("Edelkitsch"), Anfang der 1950er Jahre. Typoskript, englisch, 1 Blatt; "Project on Attitudes of German Youth", 1951: 1. "Some Remarks of the Present German Social Situation", a) Typoskript, 24 Blatt, b) Typoskript mit handschriftlichen Korrekturen, 23 Blatt, c) Typoskript, 23 Blatt, d) Typoskript, 21 Blatt, e) Entwurf, Typoskript, 23 Blatt; 2. "Estimate for six month project on Attitudes of German Youth", 2 Blatt; Institut für Sozialforschung: "Umfrage unter Frankfurter Studenten" (Max Horkheimer: "Vorbemerkung"): Über die soziale Situation und die Einstellun der Studenten, 1952, Ergebnisse eines Praktikums zur empirischen Sozialforschung, Wintersemester 1951/52, als Typoskript vervielfältigt, gebunden, 126 Blatt;

Proceedings of the 22nd Annual Biochemical Engineering Symposium

This is the twenty-second of a series of symposia devoted to talks and posters by students about their biochemical engineering research. The first, third, fifth, ninth, twelfth, sixteenth, and twenti~th were hosted by Kansas State University, the second and fourth by the University of Nebraska- Lincoln, the sixth, seventh, tenth, thirteenth, seventeenth, and twenty-second by Iowa State University, the eighth, fourteenth, and nineteenth by the University of Missouri-Columbia, the eleventh, fifteenth, and twenty-first by Colorado State University, and the eighteenth by the University of Colorado. Next year's symposium will be at the University of Oklahoma. Symposium proceedings are edited and issued by faculty of the host institution. Because final publication usually takes place in refereed journals, articles included here are brief and often cover work in progress. ContentsC. A. Baldwin, J.P. McDonald, and L. E. Erickson, Kansas State University. Effect of Hydrocarbon Phase on Kinetic and Transport Limitations for Bioremediation of Microporous Soil J. C. Wang, S. K. Banerji, and Rakesh Bajpai, University of Missouri-Columbia. Migration of PCP in Soil-Columns in Presence of a Second Organic Phase Cheng-Hsien Hsu and Roger G. Harrison, University of Oklahoma. Bacterial Leaching of Zinc and Copper from Mining Wastes James A. Searles, Paul Todd, and Dhinakar S. Kompala, University of Colorado. Suspension Culture of Chinese Hamster Ovary Cells Utilizing Inclined Sedimentation Ron Beyerinck and Eric H. Dunlop, Colorado State University. The Effect of Feed Zone Turbulence as Measured by Laser Doppler Velocimetry on Baker's Yeast Metabolism in a Chemostat Paul Li-Hong Yeh, GraceY. Sun, Gary A. Weisman, and Rakesh Bajpai, University of Missouri-Columbia. Effect of Medium Constituents upon Membrane Composition of Insect Cells R. Shane Gold, M. M. Meagher, R. Hutkins, and T. Conway, University of Nebraska-Lincoin. Ethanol Tolerance and Carbohydrate Metabolism in Lactobacilli John Sargantanis and M. N. Karim, Colorado State University. Application of Kalman Filter and Adaptive Control in Solid Substrate Fermentation D. Vrana, M. Meagher, and R. Hutkins, University of Nebraska-Lincoln. Product Recovery Optimization in the ABE Fermentation Kalyan R. Tadikonda and Robert H. Davis, University of Colorado. Cell Separations Using Targeted Monoclonal Antibodies Against Surface Proteins Meng H. Heng and Charles E. Glatz, Iowa State University. Charged Fusion for Selective Recovery of B-Galactosidase from Cell Extract Using Hollow Fiber Ion-Exchange Membrane Adsorption Hsiu-Mei Chen, Peter J. Reilly, and Clark Ford, Iowa State University. Site-Directed Mutagenesis to Enhance Thermostability of Glucoamylase from Aspergillus: A Rational Approach P. Tuitemwong, L. E. Erickson, and D. Y. C. Fung, Kansas State University. Applications of Enzymatic Hydrolysis and Fermentation on the Reduction of Flatulent Sugars in the Rapid Hydration Hydrothermal Cooked Soy Milk Sanjeev Redkar and Robert H. Davis, University of Colorado. Crossflow Microfiltration of Yeast Suspensions Linda Henk and James C. Linden, Colorado State University, and Irving C. Anderson, Iowa State University. Evaluation of Sorghum Ensilage as an Ethanol Feedstock Marc Lipovitch and James C. Linden, Colorado State University. Stability and Biomass Feedstock Pretreatability for Simultaneous Saccharification and Fermentation Ali Demirci, Anthony L. Pometto Ill, and Kenneth E. Johnson, Iowa State University. Application of Biofilm Reactors in Lactic Acid Fermentation Michael K. Dowd, Peter I. Reilly, and WalterS. Trahanovsky, Iowa State University. Low Molecular-Weight Organic Composition of Ethanol Stillage from Corn Craig E. Forney, Meng H. Heng, John R. Luther, Mark Q. Niederauer, and Charles E. Glatz, Iowa State University. Enhancement of Protein Separation Using Genetic Engineering J. F. Shimp, J. C. Tracy, E. Lee, L. C. Davis, and L. E. Erickson, Kansas State University. Modeling Contaminant Transport, Biodegradation and Uptake by Plants in the Rhizosphere Xiaoqing Yang, L. E. Erickson, and L. T. Fan, Kansas State University. Modeling of Dispersive-Convective Characteristics in Bioremediation of Contaminated Soil Jan Johansson and Rakesh Bajpai, University of Missouri-Columbia. Fouling of Membranes J. M. Wang, S. K. Banerji, and R. K. Bajpai, University of Missouri-Columbia. Migration of Sodium-Pentachorophenol (Na-PCP) in Unsaturated and Saturated Soil-Columns J. Sweeney and M. Meagher, University of Nebraska-Lincoln. The Purification of Alpha-D-Glucuronidase from Trichoderma reesei