Tailoring molecular weight of the conjugated model polymer MEH-PPV and its structure-property relations

In der vorliegenden Arbeit wurden Struktur-Eigenschaftsbeziehungen des konjugierten Modell-Polymers MEH-PPV untersucht. Dazu wurde Fällungs-fraktionierung eingesetzt, um MEH-PPV mit unterschiedlichem Molekulargewicht (Mw) zu erhalten, insbesondere MEH-PPV mit niedrigem Mw, da dieses für optische Wellenleiterbauelemente optimal geeignet ist Wir konnten feststellen, dass die Präparation einer ausreichenden Menge von MEH-PPV mit niedrigem Mw und geringer Mw-Verteilung wesentlich von der geeigneten Wahl des Lösungsmittels und der Temperatur während der Zugabe des Fällungsmittels abhängt. Alternativ dazu wurden UV-induzierte Kettenspaltungseffekte untersucht. Wir folgern aus dem Vergleich beider Vorgehensweisen, dass die Fällungsfraktionierung verglichen mit der UV-Behandlung besser geeignet ist zur Herstellung von MEH-PPV mit spezifischem Mw, da das UV-Licht Kettendefekte längs des Polymerrückgrats erzeugt. 1H NMR and FTIR Spektroskopie wurden zur Untersuchung dieser Kettendefekte herangezogen. Wir konnten außerdem beobachten, dass die Wellenlängen der Absorptionsmaxima der MEH-PPV Fraktionen mit der Kettenlänge zunehmen bis die Zahl der Wiederholeinheiten n  110 erreicht ist. Dieser Wert ist signifikant größer als früher berichtet. rnOptische Eigenschaften von MEH-PPV Wellenleitern wurden untersucht und es konnte gezeigt werden, dass sich die optischen Konstanten ausgezeichnet reproduzieren lassen. Wir haben die Einflüsse der Lösungsmittel und Temperatur beim Spincoaten auf Schichtdicke, Oberflächenrauigkeit, Brechungsindex, Doppelbrechung und Wellenleiter-Dämpfungsverlust untersucht. Wir fanden, dass mit der Erhöhung der Siedetemperatur der Lösungsmittel die Schichtdicke und die Rauigkeit kleiner werden, während Brechungsindex, Doppelbrechung sowie Wellenleiter-Dämpfungsverluste zunahmen. Wir schließen daraus, dass hohe Siedetemperaturen der Lösungsmittel niedrige Verdampfungsraten erzeugen, was die Aggregatbildung während des Spincoatings begünstigt. Hingegen bewirkt eine erhöhte Temperatur während der Schichtpräparation eine Erhöhung von Schichtdicke und Rauhigkeit. Jedoch nehmen Brechungsindex und der Doppelbrechung dabei ab.rn Für die Schichtpräparation auf Glassubstraten und Quarzglas-Fasern kam das Dip-Coating Verfahren zum Einsatz. Die Schichtdicke der Filme hängt ab von Konzentration der Lösung, Transfergeschwindigkeit und Immersionszeit. Mit Tauchbeschichtung haben wir Schichten von MEH-PPV auf Flaschen-Mikroresonatoren aufgebracht zur Untersuchung von rein-optischen Schaltprozessen. Dieses Verfahren erweist sich insbesondere für MEH-PPV mit niedrigem Mw als vielversprechend für die rein-optische Signalverarbeitung mit großer Bandbreite.rn Zusätzlich wurde auch die Morphologie dünner Schichten aus anderen PPV-Derivaten mit Hilfe von FTIR Spektroskopie untersucht. Wir konnten herausfinden, dass der Alkyl-Substitutionsgrad einen starken Einfluss auf die mittlere Orientierung der Polymerrückgrate in dünnen Filmen hat.rn

Laser shock peening treatment to control and moderate fatigue crack growth in aircraft structure based on residual stress engineering approach

Laser Shock Peening (LSP) is a surface enhancement treatment which induces a significant layer of beneficial compressive residual stresses of up to several mm underneath the surface of metal components in order to improve the detrimental effects of the crack growth behavior rate in it. The aim of this thesis is to predict the crack growth behavior in metallic specimens with one or more stripes which define the compressive residual stress area induced by the Laser Shock Peening treatment. The process was applied as crack retardation stripes perpendicular to the crack propagation direction with the object of slowing down the crack when approaching the peened stripes. The finite element method has been applied to simulate the redistribution of stresses in a cracked model when it is subjected to a tension load and to a compressive residual stress field, and to evaluate the Stress Intensity Factor (SIF) in this condition. Finally, the Afgrow software is used to predict the crack growth behavior of the component following the Laser Shock Peening treatment and to detect the improvement in the fatigue life comparing it to the baseline specimen. An educational internship at the “Research & Technologies Germany – Hamburg” department of AIRBUS helped to achieve knowledge and experience to write this thesis. The main tasks of the thesis are the following: •To up to date Literature Survey related to “Laser Shock Peening in Metallic Structures” •To validate the FE model developed against experimental measurements at coupon level •To develop design of crack growth slowdown in Centered Cracked Tension specimens based on residual stress engineering approach using laser peened strip transversal to the crack path •To evaluate the Stress Intensity Factor values for Centered Cracked Tension specimens after the Laser Shock Peening treatment via Finite Element Analysis •To predict the crack growth behavior in Centered Cracked Tension specimens using as input the SIF values evaluated with the FE simulations •To validate the results by means of experimental tests

Soil-structure interaction during tunnelling in urban area: observations and 3D numerical modelling

This work illustrates a soil-tunnel-structure interaction study performed by an integrated,geotechnical and structural,approach based on 3D finite element analyses and validated against experimental observations.The study aims at analysing the response of reinforced concrete framed buildings on discrete foundations in interaction with metro lines.It refers to the case of the twin tunnels of the Milan (Italy) metro line 5,recently built in coarse grained materials using EPB machines,for which subsidence measurements collected along ground and building sections during tunnelling were available.Settlements measured under freefield conditions are firstly back interpreted using Gaussian empirical predictions. Then,the in situ measurements’ analysis is extended to include the evolving response of a 9 storey reinforced concrete building while being undercrossed by the metro line.In the finite element study,the soil mechanical behaviour is described using an advanced constitutive model. This latter,when combined with a proper simulation of the excavation process, proves to realistically reproduce the subsidence profiles under free field conditions and to capture the interaction phenomena occurring between the twin tunnels during the excavation. Furthermore, when the numerical model is extended to include the building, schematised in a detailed manner, the results are in good agreement with the monitoring data for different stages of the twin tunnelling. Thus, they indirectly confirm the satisfactory performance of the adopted numerical approach which also allows a direct evaluation of the structural response as an outcome of the analysis. Further analyses are also carried out modelling the building with different levels of detail. The results highlight that, in this case, the simplified approach based on the equivalent plate schematisation is inadequate to capture the real tunnelling induced displacement field. The overall behaviour of the system proves to be mainly influenced by the buried portion of the building which plays an essential role in the interaction mechanism, due to its high stiffness.

The oxidation capacity of the atmosphere - OH and HO 2 radical measurements in a boreal forest environment using laser induced fluorescence spectroscopy

Das wichtigste Oxidationsmittel für den Abbau flüchtiger Kohlenwasserstoffverbindungen (VOC, engl.: volatile organic compounds) in der Atmosphäre ist das Hydroxylradikal (OH), welches sich in einem schnellen chemischen Gleichgewicht mit dem Hydroperoxylradical (HO2) befindet. Bisherige Messungen und Modellvergleiche dieser Radikalspezies in Waldgebieten haben signifikante Lücken im Verständnis der zugrundeliegenden Prozesse aufgezeigt.rnIm Rahmen dieser Doktorarbeit wurden Messungen von OH- und HO2-Radikalen mittelsrnlaserinduzierten Fluoreszensmesstechnik (LIF, engl.: laser-induced fluorescence) in einem Nadelwald in Süd-Finnland während der Messkampagne HUMPPA–COPEC–2010 (Hyytiälä United Measurements of Photochemistry and Particles in Air – Comprehensive Organic Precursor Emission and Concentration study) im Sommer 2010 durchgeführt. Unterschiedliche Komponenten des LIF-Instruments wurden verbessert. Eine modifizierte Methode zur Bestimmung des Hintergrundsignals (engl.: InletPreInjector technique) wurde in den Messaufbaurnintegriert und erstmals zur Messung von atmosphärischem OH verwendet. Vergleichsmessungen zweier Instrumente basierend auf unterschiedlichen Methoden zur Messung von OH-Radikalen, chemische Ionisationsmassenspektrometrie (CIMS - engl.: chemical ionization mass spectrometry) und LIF-Technik, zeigten eine gute Übereinstimmung. Die Vergleichsmessungen belegen das Vermögen und die Leistungsfähigkeit des modifizierten LIF-Instruments atmosphärische OH Konzentrationen akkurat zu messen. Nachfolgend wurde das LIF-Instrument auf der obersten Plattform eines 20m hohen Turmes positioniert, um knapp oberhalb der Baumkronen die Radikal-Chemie an der Schnittstelle zwischen Ökosystem und Atmosphäre zu untersuchen. Umfangreiche Messungen - dies beinhaltet Messungen der totalen OH-Reaktivität - wurden durchgeführt und unter Verwendung von Gleichgewichtszustandsberechnungen und einem Boxmodell, in welches die gemessenen Daten als Randbedingungen eingehen, analysiert. Wenn moderate OH-Reaktivitäten(k′(OH)≤ 15 s−1) vorlagen, sind OH-Produktionsraten, die aus gemessenen Konzentrationen von OH-Vorläuferspezies berechnet wurden, konsistent mit Produktionsraten, die unter der Gleichgewichtsannahme von Messungen des totalen OH Verlustes abgeleitet wurden. Die primären photolytischen OH-Quellen tragen mit einem Anteil von bis zu einem Drittel zur Gesamt-OH-Produktion bei. Es wurde gezeigt, dass OH-Rezyklierung unter Bedingungen moderater OH-Reaktivität hauptsächlich durch die Reaktionen von HO2 mit NO oder O3 bestimmt ist. Während Zeiten hoher OH-Reaktivität (k′(OH) > 15 s−1) wurden zusätzliche Rezyklierungspfade, die nicht über die Reaktionen von HO2 mit NO oder O3, sondern direkt OH bilden, aufgezeigt.rnFür Hydroxylradikale stimmen Boxmodell-Simulationen und Messungen gut übereinrn(OHmod/OHobs=1.04±0.16), während HO2-Mischungsverhältnisse in der Simulation signifikant unterschätzt werden (HO2mod/HO2obs=0.3±0.2) und die simulierte OH-Reaktivität nicht mit der gemessenen OH-Reaktivität übereinstimmt. Die gleichzeitige Unterschätzung der HO2-Mischungsverhältnisse und der OH-Reaktivität, während OH-Konzentrationen von der Simulation gut beschrieben werden, legt nahe, dass die fehlende OH-Reaktivität in der Simulation eine noch unberücksichtigte HO2-Quelle darstellt. Zusätzliche, OH-unabhängigernRO2/HO2-Quellen, wie z.B. der thermische Zerfall von herantransportiertem peroxyacetylnitrat (PAN) und die Photolyse von Glyoxal sind indiziert.

Measurement of LSP-induced residual stresses and fatigue life on thin-walled aluminium alloys specimens

This thesis work encloses activities carried out in the Laser Center of the Polytechnic University of Madrid and the laboratories of the University of Bologna in Forlì. This thesis focuses on the superficial mechanical treatment for metallic materials called Laser Shock Peening (LSP). This process is a surface enhancement treatment which induces a significant layer of beneficial compressive residual stresses underneath the surface of metal components in order to improve the detrimental effects of the crack growth behavior rate in it. The innovation aspect of this work is the LSP application to specimens with extremely low thickness. In particular, after a bibliographic study and comparison with the main treatments used for the same purposes, this work analyzes the physics of the operation of a laser, its interaction with the surface of the material and the generation of the surface residual stresses which are fundamentals to obtain the LSP benefits. In particular this thesis work regards the application of this treatment to some Al2024-T351 specimens with low thickness. Among the improvements that can be obtained performing this operation, the most important in the aeronautic field is the fatigue life improvement of the treated components. As demonstrated in this work, a well-done LSP treatment can slow down the progress of the defects in the material that could lead to sudden failure of the structure. A part of this thesis is the simulation of this phenomenon using the program AFGROW, with which have been analyzed different geometric configurations of the treatment, verifying which was better for large panels of typical aeronautical interest. The core of the LSP process are the residual stresses that are induced on the material by the interaction with the laser light, these can be simulated with the finite elements but it is essential to verify and measure them experimentally. In the thesis are introduced the main methods for the detection of those stresses, they can be mechanical or by diffraction. In particular, will be described the principles and the detailed realization method of the Hole Drilling measure and an introduction of the X-ray Diffraction; then will be presented the results I obtained with both techniques. In addition to these two measurement techniques will also be introduced Neutron Diffraction method. The last part refers to the experimental tests of the fatigue life of the specimens, with a detailed description of the apparatus and the procedure used from the initial specimen preparation to the fatigue test with the press. Then the obtained results are exposed and discussed.

Regulation and structure of YahD, a copper-inducible / serine hydrolase of Lactococcus lactis IL1403

Lactococcus lactis IL1403 is a lactic acid bacterium that is used widely for food fermentation. Copper homeostasis in this organism chiefly involves copper secretion by the CopA copper ATPase. This enzyme is under the control of the CopR transcriptional regulator. CopR not only controls its own expression and that of CopA, but also that of an additional three operons and two monocistronic genes. One of the genes under the control of CopR, yahD, encodes an α/β-hydrolase. YahD expression was induced by copper and cadmium, but not by other metals or oxidative or nitrosative stress. The three-dimensional structure of YahD was determined by X-ray crystallography to a resolution of 1.88 Å. The protein was found to adopt an α/β-hydrolase fold with the characteristic Ser-His-Asp catalytic triad. Functional testing of YahD for a wide range of substrates for esterases, lipases, epoxide hydrolases, phospholipases, amidases and proteases was, however, unsuccessful. A copper-inducible serine hydrolase has not been described previously and YahD appears to be a new functional member of this enzyme family.

Broadband Fourier transform rotational spectroscopy for structure determination: The water heptamer

Over the recent years chirped-pulse, Fourier-transform microwave (CP-FTMW) spectrometers have chan- ged the scope of rotational spectroscopy. The broad frequency and large dynamic range make possible structural determinations in molecular systems of increasingly larger size from measurements of heavy atom (13C, 15N, 18O) isotopes recorded in natural abundance in the same spectrum as that of the parent isotopic species. The design of a broadband spectrometer operating in the 2–8 GHz frequency range with further improvements in sensitivity is presented. The current CP-FTMW spectrometer performance is benchmarked in the analyses of the rotational spectrum of the water heptamer, (H2O)7, in both 2– 8 GHz and 6–18 GHz frequency ranges. Two isomers of the water heptamer have been observed in a pulsed supersonic molecular expansion. High level ab initio structural searches were performed to pro- vide plausible low-energy candidates which were directly compared with accurate structures provided from broadband rotational spectra. The full substitution structure of the most stable species has been obtained through the analysis of all possible singly-substituted isotopologues (H218O and HDO), and a least-squares rm(1) geometry of the oxygen framework determined from 16 different isotopic species compares with the calculated O–O equilibrium distances at the 0.01 Å level.

Broadband Fourier transform rotational spectroscopy for structure determination: The water heptamer

Over the recent years chirped-pulse, Fourier-transform microwave (CP-FTMW) spectrometers have changed the scope of rotational spectroscopy. The broad frequency and large dynamic range make possible structural determinations in molecular systems of increasingly larger size from measurements of heavy atom (C-13, N-15, O-18) isotopes recorded in natural abundance in the same spectrum as that of the parent isotopic species. The design of a broadband spectrometer operating in the 2-8 GHz frequency range with further improvements in sensitivity is presented. The current CP-FTMW spectrometer performance is benchmarked in the analyses of the rotational spectrum of the water heptamer, (H2O)(7), in both 2-8 GHz and 6-18 GHz frequency ranges. Two isomers of the water heptamer have been observed in a pulsed supersonic molecular expansion. High level ab initio structural searches were performed to provide plausible low-energy candidates which were directly compared with accurate structures provided from broadband rotational spectra. The full substitution structure of the most stable species has been obtained through the analysis of all possible singly-substituted isotopologues ((H2O)-O-18 and HDO), and a least-squares r(m)((1)) geometry of the oxygen framework determined from 16 different isotopic species compares with the calculated O-O equilibrium distances at the 0.01 angstrom level. (C) 2013 Elsevier B.V. All rights reserved.

Investigating the Effects of Various Crowd Characteristics on the Dynamic Properties of an Occupied Structure

One of the challenges for structural engineers during design is considering how the structure will respond to crowd-induced dynamic loading. It has been shown that human occupants of a structure do not simply add mass to the system when considering the overall dynamic response of the system, but interact with it and may induce changes of the dynamic properties from those of the empty structure. This study presents an investigation into the human-structure interaction based on several crowd characteristics and their effect on the dynamic properties of an empty structure. The dynamic properties including frequency, damping, and mode shapes were estimated for a single test structure by means of experimental modal analysis techniques. The same techniques were utilized to estimate the dynamic properties when the test structure was occupied by a crowd with different combinations of size, posture, and distribution. The goal of this study is to isolate the occupant characteristics in order to determine the significance of each to be considered when designing new structures to avoid crowd serviceability issues. The results are presented and summarized based on the level of influence of each characteristic. The posture that produces the most significant effects based on the scope of this research is standing with bent knees with a maximum decrease in frequency of the first mode of the empty structure by 32 percent atthe highest mass ratio. The associated damping also increased 36 times the damping of the empty structure. In addition to the analysis of the experimental data, finite element models and a two degree-of-freedom model were created. These models were used to gain an understanding of the test structure, model a crowd as an equivalent mass, and also to develop a single degree-of-freedom (SDOF) model to best represent a crowd of occupants based on the experimental results. The SDOF models created had an averagefrequency of 5.0 Hz, within the range presented in existing biomechanics research, and combined SDOF systems of the test structure and crowd were able to reproduce the frequency and damping ratios associated with experimental tests. Results of this study confirmed the existence of human-structure interaction andthe inability to simply model a crowd as only additional mass. The two degree-offreedom model determined was able to predict the change in natural frequency and damping ratio for a structure occupied by multiple group sizes in a single posture. These results and model are the preliminary steps in the development of an appropriate methodfor modeling a crowd in combination with a more complex FE model of the empty structure.

Claudin-1 induced sealing of blood-brain barrier tight junctions ameliorates chronic experimental autoimmune encephalomyelitis

In experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis (MS), loss of the blood-brain barrier (BBB) tight junction (TJ) protein claudin-3 correlates with immune cell infiltration into the CNS and BBB leakiness. Here we show that sealing BBB TJs by ectopic tetracycline-regulated expression of the TJ protein claudin-1 in Tie-2 tTA//TRE-claudin-1 double transgenic C57BL/6 mice had no influence on immune cell trafficking across the BBB during EAE and furthermore did not influence the onset and severity of the first clinical disease episode. However, expression of claudin-1 did significantly reduce BBB leakiness for both blood borne tracers and endogenous plasma proteins specifically around vessels expressing claudin-1. In addition, mice expressing claudin-1 exhibited a reduced disease burden during the chronic phase of EAE as compared to control littermates. Our study identifies BBB TJs as the critical structure regulating BBB permeability but not immune cell trafficking into CNS during EAE, and indicates BBB dysfunction is a potential key event contributing to disease burden in the chronic phase of EAE. Our observations suggest that stabilizing BBB barrier function by therapeutic targeting of TJs may be beneficial in treating MS, especially when anti-inflammatory treatments have failed.

Sodium nitroprusside induces cell death and cytoskeleton degradation in adult rat cardiomyocytes in vitro: implications for anthracycline-induced cardiotoxicity

Sodium nitroprusside (SNP) is used clinically as a rapid-acting vasodilator and in experimental models as donor of nitric oxide (NO). High concentrations of NO have been reported to induce cardiotoxic effects including apoptosis by the formation of reactive oxygen species. We have therefore investigated effects of SNP on the myofibrillar cytoskeleton, contractility and cell death in long-term cultured adult rat cardiomyocytes at different time points after treatment. Our results show, that SNP treatment at first results in a gradual increase of cytoskeleton degradation marked by the loss of actin labeling and fragmentation of sarcomeric structure, followed by the appearance of TUNEL-positive nuclei. Already lower doses of SNP decreased contractility of cardiomyocytes paced at 2 Hz without changes of intracellular calcium concentration. Ultrastructural analysis of the cultured cells demonstrated mitochondrial changes and disintegration of sarcomeric alignment. These adverse effects of SNP in cardiomyocytes were reminiscent of anthracycline-induced cardiotoxicity, which also involves a dysregulation of NO with the consequence of myofibrillar degradation and ultimately cell death. An inhibition of the pathways leading to the generation of reactive NO products, or their neutralization, may be of significant therapeutic benefit for both SNP and anthracycline-induced cardiotoxicity.

Investigation of Human-Structure Interaction Through Experimental and Analytical Studies

Vibration serviceability is a widely recognized design criterion for assembly-type structures, such as stadiums, that are likely subjected to rhythmic human-induced excitation. Human-induced excitation of a structure occurs from the movement of the occupants such as walking, running, jumping, or dancing. Vibration serviceability is based on the level of comfort that people have with the vibrations of a structure. Current design guidance uses the natural frequency of the structure to assess vibration serviceability. However, a phenomenon known as human-structure interaction suggests that there is a dynamic interaction between the structure and passive occupants, altering the natural frequency of the system. Human-structure interaction is dependent on many factors, including the dynamic properties of the structure, posture of the occupants, and relative size of the crowd. It is unknown if the shift in natural frequency due to humanstructure interaction is significant enough to warrant consideration in the design process. This study explores the interface of both structural and crowd characteristics through experimental testing to determine if human-structure interaction should be considered because of its potential impact on serviceability assessment. An experimental test structure that represents the dynamic properties of a cantilevered stadium structure was designed and constructed. Experimental modal analysis was implemented to determine the dynamic properties of the empty test structure and when occupied with up to seven people arranged in different locations and postures. Comparisons of the dynamic properties were made between the empty and occupied testing configurations and analytical results from the use of a dynamic crowd model recommended from the Joint Working Group of Europe. Data trends lead to the development of a refined dynamic crowd model. This dynamic model can be used in conjunction with a finite element model of the test structure to estimate the dynamic influence due to human-structure interaction due to occupants standing with straight knees. In the future, the crowd model will be refined and can aid in assessing the dynamic properties of in-service stadium structures.

Collision-Induced Dissociation Of Dipeptides In Negative Ion Electrospray Ionization Tandem Mass Spectrometry

This purpose of this project was to investigate the collision-induced dissociation of dipeptides in negative ion electrospray ionization tandem mass spectrometry, with a focus on the mechanism of the production of imidazole-type fragments not previously reported from the fragmentation of the dipeptides being studied. The majority of the dipeptides studied were alanine N-terminal or serine C-terminal dipeptides. All dipeptides were dissolved in 50:50 methanol:water, 3 mM ammonium formate. Collision-induced dissociation in the collision cell of a triple quadrupole mass spectrometer was used to fragment [M-H]- precursor ions. Accurate mass measurements confirmed the molecular formula of the imidazole-type fragments. Further MS/MS studies were performed to provide information about the fragmentation mechanism for the formation of the imidazole-type fragments. The m/z values of intermediate ions in the formation of the imidazole-type fragments were confirmed through second-generation product ion scans and precursor ion scans. More sophisticated instrumentation will be required to further probe the structure of the intermediate ions.

A Computational Analysis of the Collision-Induced Dissociation Mechanisms of the Dipeptide Glycine-Serine Under Mass Spectrometry

Collision-induced dissociation (CID) of peptides using tandem mass spectrometry (MS) has been used to determine the identity of peptides and other large biological molecules. Mass spectrometry (MS) is a useful tool for determining the identity of molecules based on their interaction with electromagnetic fields. If coupled with another method like infrared (IR) vibrational spectroscopy, MS can provide structural information, but in its own right, MS can only provide the mass-to-charge (m/z) ratio of the fragments produced, which may not be enough information to determine the mechanism of the collision-induced dissociation (CID) of the molecule. In this case, theoretical calculations provide a useful companion for MS data and yield clues about the energetics of the dissociation. In this study, negative ion electrospray tandem MS was used to study the CID of the deprotonated dipeptide glycine-serine (Gly-Ser). Though negative ion MS is not as popular a choice as positive ion MS, studies by Bowie et al. show that it yields unique clues about molecular structure which complement positive ion spectroscopy, such as characteristic fragmentations like the loss of formaldehyde from the serine residue.2 The increase in the collision energy in the mass spectrometer alters the flexibility of the dipeptide backbone, enabling isomerizations (reactions not resulting in a fragment loss) and dissociations to take place. The mechanism of the CID of Gly-Ser was studied using two computational methods, B3LYP/6-311+G* and M06-2X/6-311++G**. The main pathway for molecular dissociation was analyzed in 5 conformers in an attempt to verify the initial mechanism proposed by Dr. James Swan after examination of the MS data. The results suggest that the loss of formaldehyde from serine, which Bowie et al. indicates is a characteristic of the presence of serine in a protein residue, is an endothermic reaction that is made possible by the conversion of the translational energy of the ion into internal energy as the ion collides with the inert collision gas. It has also been determined that the M06-2X functional¿s improved description of medium and long-range correlation makes it more effective than the B3LYP functional at finding elusive transition states. M06-2X also more accurately predicts the energy of those transition states than does B3LYP. A second CID mechanism, which passes through intermediates with the same m/z ratio as the main pathway for molecular dissociation, but different structures, including a diketopiperazine intermediate, was also studied. This pathway for molecular dissociation was analyzed with 3 conformers and the M06-2X functional, due to its previously determined effectiveness. The results suggest that the latter pathway, which meets the same intermediate masses as the first mechanism, is lower in overall energy and therefore a more likely pathway of dissociation than the first mechanism.

Cyclin D1 (CCND1) A870G gene polymorphism modulates smoking-induced lung cancer risk and response to platinum-based chemotherapy in non-small cell lung cancer (NSCLC) patients

PURPOSE: The cyclin D1 (CCND1) A870G gene polymorphism is linked to the outcome in patients with resectable non-small cell lung cancer (NSCLC). Here, we investigated the impact of this polymorphism on smoking-induced cancer risk and clinical outcome in patients with NSCLC stages I-IV. METHODS: CCND1 A870G genotype was determined by polymerase chain reaction (PCR) and restriction fragment length polymorphism analysis (RFLP) of DNA extracted from blood. The study included 244 NSCLC patients and 187 healthy control subjects. RESULTS: Patient characteristics were: 70% male, 77% smokers, 43% adenocarcinoma, and 27% squamous cell carcinoma. Eighty-one percent of the patients had stages III-IV disease. Median age at diagnosis was 60 years and median survival was 13 months. Genotype frequencies of patients and controls both conformed to the Hardy Weinberg equilibrium. The GG genotype significantly correlated with a history of heavy smoking (>or=40 py, P=0.02), and patients with this genotype had a significantly higher cigarette consumption than patients with AA/AG genotypes (P=0.007). The GG genotype also significantly correlated with tumor response or stabilization after a platinum-based first-line chemotherapy (P=0.04). Survival analysis revealed no significant differences among the genotypes. CONCLUSION: Evidence was obtained that the CCND1 A870G gene polymorphism modulates smoking-induced lung cancer risk. Further studies are required to explore the underlying molecular mechanisms and to test the value of this gene polymorphism as a predictor for platinum-sensitivity in NSCLC patients.