Analytical theory for proton correlations in common water ice IhI_h

We provide a fully analytical microscopic theory for the proton correlations in water ice $I_h$. We compute the full diffuse elastic neutron scattering structure factor, which we find to be in excellent quantitative agreement with Monte Carlo simulations. It is also in remarkable qualitative agreement with experiment, in the absence of any fitting parameters. Our theory thus provides a tractable analytical starting point to account for more delicate features of the proton correlations in water ice. In addition, it directly determines an effective field theory of water ice as a topological phase.Comment: 5 pages, 3 figure

Studies of Protein-Protein and Protein-Water Interactions by Small Angle X-Ray Scattering, Terahertz Spectroscopy, ASMOS, And Computer Simulation

The protein folding problem has been one of the most challenging subjects in biological physics due to its complexity. Energy landscape theory based on statistical mechanics provides a thermodynamic interpretation of the protein folding process. We have been working to answer fundamental questions about protein-protein and protein-water interactions, which are very important for describing the energy landscape surface of proteins correctly. At first, we present a new method for computing protein-protein interaction potentials of solvated proteins directly from SAXS data. An ensemble of proteins was modeled by Metropolis Monte Carlo and Molecular Dynamics simulations, and the global X-ray scattering of the whole model ensemble was computed at each snapshot of the simulation. The interaction potential model was optimized and iterated by a Levenberg-Marquardt algorithm. Secondly, we report that terahertz spectroscopy directly probes hydration dynamics around proteins and determines the size of the dynamical hydration shell. We also present the sequence and pH-dependence of the hydration shell and the effect of the hydrophobicity. On the other hand, kinetic terahertz absorption (KITA) spectroscopy is introduced to study the refolding kinetics of ubiquitin and its mutants. KITA results are compared to small angle X-ray scattering, tryptophan fluorescence, and circular dichroism results. We propose that KITA monitors the rearrangement of hydrogen bonding during secondary structure formation. Finally, we present development of the automated single molecule operating system (ASMOS) for a high throughput single molecule detector, which levitates a single protein molecule in a 10 µm diameter droplet by the laser guidance. I also have performed supporting calculations and simulations with my own program codes

Development of new green strategies based on Brønsted and Lewis acid catalysis in organic synthesis

Environmental protection is one of the greatest themes of the XXI century. For what concerns chemistry, in the early 1990’s, even before its current formal and exhaustive definition, given by Paul T. Anastas and John C. Warner in 1998, the term "green chemistry" starts to appear in the literature. Anastas and Warner formulated a list of 12 principles, that constitute the most complete definition of green chemistry. Herein, an effort towards the fulfillment of these principles is presented with respect to: 1) the development of a catalytic system based on hydrate ferric sulfate for the hydration of internal alkynes; 2) an approach to the synthesis of a new family of chiral phosphates for organocatalysis

Van-der-Waals-Wechselwirkungen: Präzise Struktur und Dynamik von Molekülen

In dieser Arbeit wurden fünf molekulare Spezies mit großamplitudigen Bewegungen verschiedener Gruppen des Typus XH (X = CH2, N, O) spektroskopisch untersucht: Allylmethyldisulfid, Methyl-3,3,3-Trifluorpyruvat, Acetylacetylen, Acetoncyanhydrin und der 2,2,4,4-Tetrafluor-1,3-dithietan-Ammoniak Komplex. Neben einer Analyse der aus der internen Rotation resultierenden Feinstruktur der Rotationsspektren konnten über die planaren Momente Aussagen über die Molekülstruktur getroffen werden. Durch Analyse von Isotopologen der schweren Elemente konnte zu sätzlich eine semi-experimentelle Struktur des 2,2,4,4-Tetrafluor-1,3-dithietan-Ammoniak Komplexes mithilfe der Kraitchman-Gleichungen ermittelt werden. Im Zusammenspiel mit einer Analyse der natürlichen Bindungsorbitale (NBO) konnten die entscheidenden bindenden Wechselwirkungen im Komplex identifiziert werden. Auf Grundlage dieser Untersuchungen wurden Methoden hinsichtlich ihres Prognosepotentials der für großamplitudige Bewegungen charakteristischen Parameter überprüft. Zunächst wurde anhand der Korrelation publizierter Barrierehöhen der internen Methylrotation und essentiellem Tunnelparameter des Programms ERHAM zur Spektrenanpassung dessen inertiale Vorhersage ermöglicht. Eine einfache quantenchemische Berechnung dieses Parameters ist demgegenüber nicht möglich. In Analogie wurde ein Zusammenhang zwischen der Energieaufspaltung der Tunnelzustände und der Barrierehöhe zur Tunnelbewegung zwischen äquivalenten gauche-Konformationen von Alkoholen gefunden. Abschließend wurden quantenchemische Methoden zur Vorhersage von Barrierehöhen des Hinderungspotentials zur interner Methylgruppenrotation getestet und qualitative Begründungen sowie eine Einordnung nach Substanzklassen gegeben: Es wurden Ethanderivate, Acetylspezies, Methylester und -sulfide, hinsichtlich der Reproduzierbarkeit von experimentell ermittelten Barrierehöhen durch die Kopplung von zwei quantenchemischen Methoden überprüft (Ansatz 1). Als zweiter Ansatz wurden für rudimentärere Rechnungen einzelner Substanzklassen Skalierungsfaktoren eingeführt, um deren mittlere Abweichung deutlich zu reduzieren. So wurden in dieser Studie insgesamt mehr als 100 Spezies untersucht. Der erste Ansatz bildet die Barrieren sehr gut ab und kann dadurch als Standardmethode für die Vorhersage weiterer, bisher nicht systematisch untersuchter Substanzklassen verwendet werden.In this work, five molecular species with large amplitude motions of different groups of type XH (X = CH2, N, O) were studied by spectroscopy: Allyl methyl disulfide, methyl 3,3,3-trifluoropyruvate, acetylacetylene, acetone cyanohydrine, and the 2,2,4,4-tetrafluoro-1,3-dithietane-ammonia complex. The fine structure of the rotational spectra resulting from the internal rotation could be analyzed and conclusions about the molecular structure could be drawn with the help of planar moments. Additionally, by analyzing isotopologues of the heavy elements, a semi-experimental structure of the 2,2,4,4-tetrafluoro-1,3-dithietane-ammonia complex was determined using the Kraitchman equations. In combination with an analysis of the natural bond orbitals (NBO), the crucial binding interactions in the complex were identified. Based on these studies, methods were evaluated in terms of their predictive potential of the parameters characteristic of large amplitude motions. First, based on the correlation of published barrier heights of internal methyl rotation and the essential tunneling parameters of the program for spectral analysis (ERHAM) for the latter was obtained. Conversly, a simple quantum chemical determination of this parameter is not possible. Analogously, a correlation was found between the energy splitting of the tunneling states and the barrier height to tunneling motion between equivalent gauche conformations of alcohols. Finally, quantum chemical methods for predicting barrier heights of the hindering potential to internal methyl group rotation were tested, and qualitative justifications and classifications by substance class are provided: Ethane derivatives, acetyl species, methyl esters and -sulfides, were studied with respect to the reproducibility of experimentally determined barrier heights by coupling two quantum hemical methods (approach 1). As a second approach, scaling factors for the individual substance classes were introduced for more rudimentary calculations to significantly reduce their mean deviations. Thus, a total of more than 100 species were examined in this study. The first approach reproduces the barriers very well and can thereby be sed as standard method for the prediction of other substance classes that have not been systematically investigated yet.Fonds der chemischen Industrie/Kekulé-Stipendium/104490/E

NASA-HBCU Space Science and Engineering Research Forum Proceedings

The proceedings of the Historically Black Colleges and Universities (HBCU) forum are presented. A wide range of research topics from plant science to space science and related academic areas was covered. The sessions were divided into the following subject areas: Life science; Mathematical modeling, image processing, pattern recognition, and algorithms; Microgravity processing, space utilization and application; Physical science and chemistry; Research and training programs; Space science (astronomy, planetary science, asteroids, moon); Space technology (engineering, structures and systems for application in space); Space technology (physics of materials and systems for space applications); and Technology (materials, techniques, measurements)

Protection Against Radiation Hazards in Space, Book I Proceedings of the Symposium at Gatlinburg, Tenn., Nov. 5-7, 1962

Protection against radiation hazards in spac

Synthesis and Biological Evaluation of Anticancer Agents

Within the last ten years intense research has led to a greater understanding of the signalling pathways that control normal cell division and cancerous cell proliferation. Enzymes known as protein tyrosine kinases (PTKs) play a key role in such growth-related processes by catalysing the phosphorylation of tyrosine residues on intracellular protein substrates. This knowledge has led to the search for selective PTK inhibitors in the hope of generating chemotherapeutic agents of potential use in the treatment of cancer. Particular attention has focused on the signalling events that occur at a receptor tyrosine kinase (RTK) called the epidermal growth factor (EGF) receptor since a number of studies have implicated its involvement in many types of human cancer. Compounds found to possess anticancer activity by acdng as PTK inhibitors with a structural resemblance to tyrosine are known as the tyrphostins. In this project, an extensive array of 3-arylpropenonitriles (approximately 140 compounds) akin to the tyrphostins have been synthesised and biologically evaluated in cell assays designed to correlate PTK inhibition at the EGF receptor to antiproliferative activity. Efforts were directed at producing more stable tyrphostin analogues as well as those that incorporate a heterocyclic moiety. From initial studies, tyrphostins incorporadng a nitrothiophene portion were shown to be highly potent antiproliferative agents and gave sub-nanomolar IC50 values against the breast adenocarcinoma MCF-7 cell line. Consequently, structurally isomeric tyrphostin sets were synthesised. More detailed biological analysis demonstrated that some of these compounds were acting in a non-selective cytotoxic fashion. Presently, the compound ethyl 2-cyano-3-[5-(2-nitrothienyl)]propenoate (A) has been accepted by the National Cancer Institute to undergo an in vivo evaluation and represents an interesting new cytotoxic anticancer agent. During a search for heterocyclic tyrphostins some quinoline derivatives were found to display encouraging antiproliferative activities against the MCF-7 cell line (IC50 values < 1 muM). The most potent compounds contained the 2-aminoethene-1,1-dicarbonitrile unit and, although they produced an additional cytotoxic action, they were found to inhibit selectively the phosphorylation of an unknown signalling protein that was found to be linked to EGF receptor activation. The 2-substituted quinoline (B) also displayed a certain degree of selectivity within a panel of 60 tumour cell lines (held at the US National Cancer Institute) and may act as an interesting lead for future studies. In order to determine the stereochemical requirement preferred for biological activity, attempts were made to synthesise geometric isomers of some tyrphostins. In particular, the cis- and trans- forms of the known tyrphostin (C) were synthesised and characterised by detailed NMR spectroscopy and X-ray crystallography. Interestingly, the isomer (C) was about 3.5 times more potent than its geometric panner in an antiproliferative assay against a cell line (HN5) that overexpresses the EGF receptor. Also, synthesised were other 2,3-diaryIpropenonitriles akin to compound (C) and some of these displayed equally effective IC50 values against the MCF-7 cell line

The effects of cholesterol lowering agents on the proteome of primary human hepatocytes

Cholesterol plays a crucial role for human life. It is a part of eukaryotic lipid bilayers, necessary for cell division and serves as a precursor for steroid hormones. The effects of cholesterol lowering agents are not yet fully understood. This study describes, for the first time, the effects of the HMG-CoA reductase inhibitor rosuvastatin and the new CYP51A1 inhibitor LEK-935 on the proteome of primary human hepatocytes. Samples derived from two different human donors were analysed. They were sub-fractionated prior to the proteome analysis to enhance the resolution of the analysis. The cytosolic and microsomal fractions were analysed in a semi-quantitative manner by 2D-PAGE and nLC-MS respectively. A final set of 44 proteins was found to be differentially expressed. This set contains proteins already known to be affected and involved in the cholesterol biosynthesis. It also contains proteins that cannot be directly related to cholesterol metabolism and that have not yet been described to be affected by cholesterol lowering agents. The finding of the already known proteins validates the chosen experimental design while the other proteins provide new information and represent targets for further investigations. RT-PCR measurements performed at a chosen set of proteins validate the results. They furthermore underline the huge inter-individual differences observed during the proteome analysis.Cholesterin ist essentiell für das menschliche Leben. Es ist integraler Bestandteil eukaryotischer Membranen, notwendig für die Zellteilung und dient als Vorläufermolekül der Steroidhormone. Die Effekte von cholesterinsenkenden Medikamenten sind bis heute noch nicht vollständig aufgeklärt. Diese Arbeit beschreibt zum ersten Mal die Effekte des HMG-CoA Inhibitors Rosuvastatin und des neuen CYP51A1 Inhibitors LEK-935 auf das Proteom primärer humaner Hepatozyten. Die cytosolische sowie die mikrosomale Fraktion von zwei menschlichen Spendern wurde mittels 2D-PAGE und nLC-MS semi-quantitative analysiert. Insgesamt wurden 44 Proteine als differenziell exprimiert gefunden. Unter diesen finden sich Proteine von denen bereits bekannt ist, dass sie beeinflusst werden und die in die Cholesterinbiosynthese involviert sind. Es finden sich aber auch Proteine die nicht direkt mit dem Cholesterinmetabolismus in Verbindung gebracht werden können und deren Beeinflussung durch cholesterinsenkende Medikamente noch nicht bekannt ist. Die bereits bekannten Proteine belegen den experimentellen Ansatz. Gleichzeitig stellen die anderen Proteine neue Informationen und damit neue Ziele für weitergehende Untersuchungen dar. Die gewonnenen Ergebnisse wurden durch RT-PCR-Analysen eines ausgewählten Sets an Proteinen bestätigt. Diese Validierungsexperimente unterstreichen darüber hinaus die großen inter-individuellen Unterschiede, die auch schon in der Proteomanalyse gefunden wurden

Aerospace Medicine and Biology. an Annotated Bibliography. 1958-1961 Literature, Volumes VII-X, Part 2

Abstracts on aerospace medicine and biology - bibliography on environmental factors, safety and survival, personnel, pharmacology, toxicology, and life support system

Aeronautical engineering: A cumulative index to a continuing bibliography

This bibliography is a cumulative index to the abstracts contained in NASA SP-7037 (197) through NASA SP-7037 (208) of Aeronautical Engineering: A Continuing Bibliography. NASA SP-7037 and its supplements have been compiled through the cooperative efforts of the American Institute of Aeronautics and Astronautics (AIAA) and the National Aeronautics and Space Administration (NASA). This cumulative index includes subject, personal author, corporate source, foreign technology, contract, report number, and accession number indexes