Experiments show that MgSO4 salt has a non-monotonic effect as a function of MgSO4 concentration on the ejection of DNA from bacteriophage lambda. There is a concentration, N0, at which the minimum amount of DNA is ejected. At lower or higher concentrations, more DNA is ejected. We propose that this non-monotonic behavior is due to the overcharging of DNA at high concentration of Mg⁺² counterions. As the Mg⁺² concentration increases from zero, the net charge of ejected DNA changes its sign from negative to positive. N0 corresponds to the concentration at which DNA is neutral. Our theory fits experimental data well. The DNA-DNA electrostatic attraction is found to be -0.004 kBT/nucleotide. Simulations of DNA-DNA interaction of a hexagonal DNA bundle support our theory. They also show the non-monotonic DNA-DNA interaction and reentrant behavior of DNA condensation by divalent counterions. Three problems in understanding the capsid assembly for a retrovirus are studied: First, the way in which the viral membrane affects the structure of in vivo assembled HIV-1 capsid is studied. We show that conical and cylindrical capsids have similar energy at high surface tension of the viral membrane, which leads to the various shapes of HIV-1 capsids. Secondly, the problem of RNA genome packaging inside spherical viruses is studied using RNA condensation theory. For weak adsorption strength of capsid protein, most RNA genomes are located at the center of the capsid. For strong adsorption strength, RNA genomes peak near the capsid surface and the amount of RNA packaged is proportional to the capsid area instead its volume. Theory fits experimental data reasonably well. Thirdly, the condensation of RNA molecules by nucleocapsid (NC) protein is studied. The interaction between RNA molecules and NC proteins is important for the reverse transcription of viral RNA which relates to the viral infectivity. For strong adsorption strength of the NC protein, there is a screening effect by RNA molecules around a single NC protein.

No description available.

La thérapie de resynchronisation cardiaque (CRT) est un traitement qui diminue la mortalité et améliore la qualité de vie des patients atteints d’insuffisance cardiaque et présentant un dyssynchronisme de la contraction ventriculaire gauche. Malgré le succès de cette thérapie, plus de 30% des patients ne présentent pas l’amélioration désirée. Plusieurs études portant sur le synchronisme électrique ou mécanique de la contraction ont été effectuées mais peu d’entres elles se sont attardées sur le couplage électromécanique à l'échelle macroscopique. Ce projet a comme objectif d’observer le comportement électromécanique des ventricules canins en présence d’un resynchronisateur cardiaque. Un logiciel a été développé pour permettre l’analyse des informations provenant de la cartographie endocardique sans contact et de la ventriculographie isotopique tomographique chez 12 sujets canins insuffisants. Pour observer la réponse mécanique suite à l’activation électrique, nous avons premièrement recalé les surfaces issues des 2 modalités. Ensuite, nous avons défini les limites du cycle cardiaque, analysé les signaux électriques et les courbes de déplacement de la paroi endocardique. Le début de la contraction est défini par un déplacement radial de 10% vers le centre du ventricule. Les résultats démontrent que la durée d’activation du ventricule gauche et la largeur du QRS augmentent en présence d’une stimulation externe et que les délais électromécaniques sont indépendants dans les modes de stimulation étudiés (sinusal, LVbasal, RVapex ou BIV) avec une moyenne de 84,56±7,19 ms. Finalement, nous avons noté que la stimulation basolatérale procure une fonction cardiaque optimale malgré une durée prolongée du QRS. / Cardiac Resynchronization Therapy (CRT) is known to decrease mortality rate and improve the quality of life for patients suffering from heart failure with left ventricular contraction dyssynchrony. However, it has been shown that 30% of patients do not respond to this therapy. Many studies have investigated the electrical or mechanical synchronism of contraction but few have studied the activation contraction coupling on a macroscopic level. The objective of this study is to observe the left ventricle’s electromechanical behaviour under biventricular stimulation. A software has been developed to analyse the data coming from non-contact mapping and blood pool SPECT for 12 dogs with heart failure. In order to observe the mechanical response following an electrical activation, we have registered 3D surfaces generated by the 2 modalities. Afterward, we defined the cardiac cycle limits, and we analyzed electrical signals as well as endocardial wall displacement curves where the onset of contraction was defined as a 10% inward radial displacement. Results show that both duration of left ventricular activation and QRS increase with pacing and that electromechanical delays are independent of stimulation mode (mean value 84,56 ± 7,19 ms). Finally, we observed that basolateral stimulation shows the best improvement for left ventricular function while presenting a long QRS duration.

In this thesis we have focussed on two types of axially symmetric ion trap mass analysers viz., the quadrupole ion trap mass analyser and the toroidal ion trap mass analyser. We have undertaken three numerical studies in this thesis, one study is on the quadrupole ion trap mass analysers and two studies are on the toroidal ion trap mass analysers. The first study is related to improvement of the sensitivity of quadrupole ion trap mass analysers operated in the resonance ejection mode. In the second study we have discussed methods to determine the multipole coefficients in the toroidal ion trap mass analysers. The third study investigates the stability of ions in the toroidal ion trap mass analysers. The first study presents a technique to cause unidirectional ion ejection in a quadrupole ion trap mass spectrometer operated in the resonance ejection mode. In this technique a modified auxiliary dipolar excitation signal is applied to the endcap electrodes. This modified signal is a linear combination of two signals. The first signal is the nominal dipolar excitation signal which is applied across the endcap electrodes and the second signal is the second harmonic of the first signal, the amplitude of the second harmonic being larger than that of the fundamental. We have investigated the effect of the following parameters on achieving unidirectional ion ejection: primary signal amplitude, ratio of amplitude of second harmonic to that of primary signal amplitude, different operating points, different scan rates, different mass to charge ratios and different damping constants. In all these simulations unidirectional ejection of destabilized ions has been successfully achieved. The second study presents methods to determine multipole coefficients for describing the potential in toroidal ion trap mass analysers. Three different methods have been presented to compute the toroidal multipole coefficients. The first method uses a least square fit and is useful when we have ability to compute potential at a set of points in the trapping region. In the second method we use the Discrete Fourier Transform of potentials on a circle in the trapping region. The third method uses surface charge distribution obtained from the Boundary Element Method to compute these coefficients. Using these multipole coefficients we have presented (1) equations of ion motion in toroidal ion traps (2) the Mathieu parameters in terms of multipole coefficients and (3) the secular frequency of ion motion in these traps. It has been shown that the secular frequency obtained from our method has a good match with that obtained from numerical trajectory simulation. The third study presents stability of ions in practical toroidal ion trap mass analysers. Here we have taken up for investigation four geometries with apertures and truncation of electrodes. The stability is obtained in UDC-VRF plane and later this is converted into A-Q plane on the Mathieu stability plot. Though the plots in terms of Mathieu parameters for these structures are qualitatively similar to the corresponding plot of linear ion trap mass analysers, there is a significant difference. The stability plots of these have regions of nonlinear resonances where ion motion is unstable. These resonances have been briefly investigated and it is proposed that they occur on account of hexapole and octopole contributions to the field in these toroidal ion traps.

Made available in DSpace on 2016-03-15T19:35:57Z (GMT). No. of bitstreams: 1 Edith Tueros Cuadros.pdf: 4357925 bytes, checksum: 7a9a7c9700e9ab1b8e24a65ab089b198 (MD5) Previous issue date: 2016-02-02 / Fundação de Amparo a Pesquisa do Estado de São Paulo / Cosmic rays are strongly influenced by solar, geomagnetic and atmospheric phenomena. CARPET detector, conceived for cosmic rays observation with energies in the range between 105 - 1012 eV, is an important tool for the study of these phenomena. The Earth s atmosphere conditions are also affected by changes in the cosmic rays flux, therefore, cosmic rays characterization is important to define physical and chemical conditions of our atmosphere. To characterize the cosmic rays flux variations, detected on the ground, prior elimination of atmospheric pressure and temperature effects on ground level is needed, thus, data recorded by meteorological instruments on CASLEO were used for that corrections. To eliminate the effect of temperature through the whole vertical atmosphere it was applied the integral and the mass-average temperature method by using vertical temperature profiles. Both methods were tested using CARPET-TEL data for the year 2009, this data were previously corrected by pressure influences. The mass-average temperature method shows a better response when comparing the corrected CARPET date with neutron monitor observations .The whole cosmic rays flux data analysis, for CARPET-TEL data corrected by integral method (for the period 2006/04/01 - 2014/06/30), shows an anti-correlation with sunspot number and a clear seasonal variation after 2008. Two Forbush decreases (FD), were detected by CARPET which were produced by geo-effective CMEs. Both FD onsets coincided with the interplanetary shock instant, which preceded intense geomagnetic storms. With these results, we can reinforce that CARPET is an important tool to study long and short term cosmic rays behavior, because it has a similar response to experiments that operates at atmosphere particle energy ranges. / Os raios cósmicos são fortemente influenciados pelos fenômenos solares, geomagnéticos e atmosféricos. O detector CARPET, concebido para a observação dos raios cósmicos com energias na faixa compreendida entre 105 e 1012 eV, é uma ferramenta importante para o estudo desses fenômenos. As condições da nossa atmosfera são também afetadas pelas variações no fluxo de raios cósmicos que chegam a Terra, portanto sua caracterização é importante para se definir as condições físicas e químicas da mesma. Para caracterizar as variações do fluxo de raios cósmicos a partir de observações no solo é necessário a eliminação prévia da influência dos efeitos da pressão e temperatura atmosférica na superfície, para tal foram utilizados dados meteorológicos obtidos no CASLEO. Para a eliminação do efeito da temperatura ao longo de toda atmosfera foram utilizados o método integral e o método de temperatura ponderada pela massa que utilizam perfis verticais de temperatura. Os dois métodos foram testados para o ano de 2009 com os dados do canal TEL do CARPET previamente corrigidos pela pressão, sendo que o método de temperatura ponderada pela massa apresentou uma resposta melhor ao se comparar os dados corrigidos com os dados observados com monitores de nêutrons. A análise de todos os dados do fluxo raios cósmicos do canal TEL do CARPET (1/04/2006 a 30/06/2014) corrigidos pelo método integral, mostra a anti-correlação com o número de manchas solares, e uma variação sazonal pronunciada após 2008. Foram detectados dois decréscimos Forbush (FD) produzidos por CMEs geo-efetivos. O início de ambos FD coincidiu com o instante do choque interplanetário, que antecedeu tempestades geomagnéticas intensas. Com estes resultados reforçamos que o CARPET é uma ferramenta importante para estudo das modulações de raios cósmicos de longo e curto prazo porque apresenta uma resposta semelhante com os experimentos que fazem observações em outras faixas de energia.

No description available.

Abstract Intracoronary administration of autologous bone marrow derived stem cells (BMC) has been postulated to repair the myocardial damage in patients who have suffered acute ST-elevation myocardial infarction (STEMI). The aim of this study was to find determinants for the left ventricular functional recovery after BMC treatment of STEMI and to study the effect of BMC treatment on different biochemical and clinical parameters associated with the outcome of STEMI patients. In this study, STEMI patients treated with thrombolysis were randomly assigned to receive either intracoronary BMC (n=39) or placebo (n=39) into the infarct related artery at the time of percutaneous coronary intervention. The efficacy of the BMC treatment was assessed by measurement of the change of left ventricular ejection fraction (LVEF) from baseline to six months after STEMI. Two-dimensional echocardiography was used to assess PA pressure, LV systolic and diastolic function. Blood samples were drawn for biochemical determinations at several time points and BMCs were cultured in the laboratory for in vitro analyses. In the BMC group, the most powerful determinant of the change of LVEF was the baseline LVEF. Patients with baseline LVEF at or below the median (≤62.5%) experienced a more marked improvement of LVEF than those above the median. Elevated levels of N-terminal probrain natriuretic peptide (NT-proBNP) and N-terminal proatrial natriuretic peptide (NT-proANP) were also associated with an improvement of LVEF in the BMC group. However, no difference was observed between the BMC group and the placebo group in the changes of the levels of NT-proANP, NT-proBNP or any of the inflammatory markers measured. The BMC group showed a trend toward a reduction of peak PA pressure, while the placebo group had a significant increase of peak PA pressure at 6 months. In addition, there was a greater improvement in the LV diastolic function, assessed in quartiles, in the BMC group. The in vitro studies of BMCs revealed that exposure to tumor necrosis factor alpha (TNF-α) significantly enhanced the proliferation of BMCs and resulted in activation of immunosuppression by altering the expression of several immunosuppressive proteins. In conclusion, low baseline LVEF as well as high levels of natriuretic peptides NT-proANP and NT-proBNP, which reflect the severity of the hemodynamic and neurohumoral reactions evoked by the myocardial damage, have a considerable association to a better response to stem cell therapy after an acute STEMI. BMC therapy also prevents the increase of PA pressure and improves the cardiac diastolic function. Based on in vitro studies, the inflammatory cytokine TNF-α seems to evoke an enhanced proliferation of the bone marrow-derived mesenchymal stem cells and activation of several immunosuppressive defence mechanisms. / Tiivistelmä Sydäninfarktipotilaiden sepelvaltimoon pallolaajennuksen yhteydessä injektoitujen kantasolujen tiedetään parantavan hieman sydämen pumppauskykyä, mutta taustalla olevaa mekanismia ei tunneta. Kantasoluhoidon onnistumiseen vaikuttavia tekijöitä on tutkittu vasta vähän, eikä myöskään sitä tiedetä, miksi kaikki potilaat eivät hyödy kantasoluhoidosta. Tämän tutkimuksen tavoitteena oli selvittää infarktialueelle annetun kantasoluhoidon vaikutuksia äkillisen ST-nousuinfarktin (STEMI) sairastaneissa potilaissa, ja etsiä hoidon onnistumiseen vaikuttavia tekijöitä. Tutkimuksessa käytettiin potilasaineistoa, johon otettiin 78 äkilliseen sydäninfarktiin sairastunutta potilasta, jotka hoidettiin liuotushoidolla ja sen jälkeen pallolaajennuksella. Puolet potilaista satunnaistettiin saamaan lumeliuosta ja puolet omaa luuydinsolukkoaan (BMC), joka ruiskutettiin pallolaajennuksen yhteydessä sepelvaltimon kautta infarktialueelle. Hoidon vaikusta tutkittiin mittaamalla angiografian avulla vasemman kammion ejektiofraktion (LVEF) muutosta lähtötilanteen ja kuuden kuukauden seurannan välillä. Lisäksi sydämen ultraäänitutkimuksella määritettiin keuhkovaltimopainetta ja vasemman kammion systolista ja diastolista toimintaa. Potilaista otettiin lisäksi verinäytteitä, joista määritettiin erilaisia tulehdusmerkkiaineita ja natriureettisia peptidejä. Lisäksi potilaista kerättyjä luuydinkantasoluja viljeltiin laboratoriossa in vitro-analyyseja varten. Tutkimuksessa todettiin, että LVEF ennen kantasoluhoitoa oli voimakkain ennustetekijä suotuisalle LVEF:n muutokselle kantasoluhoidon jälkeen. Potilaat, joilla LVEF oli ennen kantasoluhoitoa alle mediaaniarvon (≤62.5%), hyötyivät kantasoluhoidosta enemmän kuin potilaat, joilla LVEF oli yli mediaanin. Myös natriureettisten peptidien NT-proBNP:n ja NT-proANP:n korkea taso infarktin jälkeen oli yhteydessä suurempaan LVEF:n paranemiseen BMC-potilailla. Natriureettisten peptidien ja tulehdusmerkkiaineiden pitoisuuksien muutoksissa kantasoluhoidon jälkeen ei kuitenkaan todettu eroa BMC- ja kontrolliryhmän välillä. Sydämen diastolisen toiminnan havaittiin paranevan enemmän BMC-ryhmässä kuin kontrolliryhmässä. Lisäksi BMC-ryhmässä havaittiin lievää laskua keuhkovaltimopaineessa, kun taas kontrolliryhmässä se nousi merkittävästi. In vitro-tutkimukset luuytimestä erilaistetuilla mesenkymaalisilla kantasoluilla puolestaan osoittivat, että tuumorinekroositekijä alfa (TNF-α)-altistus lisäsi solujakautumista ja monien immunosupressiivisten proteiinien tuottoa soluissa. Matala LVEF sekä natriureettisten peptidien NT-proBNP:n ja NT-proANP:n korkea taso sydäninfarktin jälkeen kuvaavat infarktivaurion aiheuttamien hemodynaamisten ja neurohumoraalisten reaktioiden vakavuutta, ja tässä tutkimuksessa niiden osoitettiin olevan vahvasti yhteydessä äkillisen ST-nousuinfarktin jälkeen annetun kantasoluhoidon hyötyyn. Kantasoluhoito saattaa myös suojata infarktipotilaita haitalliselta keuhkovaltimopaineen nousulta ja parantaa sydämen diastolista toimintaa. Tulehdusvälittäjäaine TNF-α näytti in vitro-kokeiden perusteella lisäävän luuytimen mesenkymaalisten kantasolujen jakautumista ja aktivoivan niissä monia immunosuppressiivisia puolustusmekanismeja tulehdusta vastaan.

This thesis deals with the possibility of using impedance cardiography for calculating cardiac output. Kubicek’s, Sramek‘s and Sramek-Bernstein‘s methods are discussed here. These methods were applied to a data set, obtained by measuring on subjects with implanted cardiostimulators. The subjects’ heart rate was being changed by the programing of cardiostimulators. Thanks to this procedure the measured data were not affected by artifacts, connected with the heart rate change caused by a body stress, or other influences. An influence of heart rate on a cardiac output value based on the statistical processing of the data set was studied.

Le syndrome métabolique (SM) est associé avec une augmentation du risque de survenue d’évènements cardiovasculaires et plus particulièrement d’insuffisance cardiaque à fraction d’éjection préservée (ICFEp). L’ICFEp représente environ 50% des IC totales, cependant, à ce jour, aucun traitement n’a permis de diminuer significativement la mortalité. L’ICFEp associée au SM, bien que d’origine multifactorielle, est caractérisée par une activation du système endothélinergique, une surexpression du récepteur minéralocorticoïde ainsi qu’une dysfonction mitochondriale participant à l’établissement et au maintien de la pathologie. Nous avons évalué dans trois études distinctes les effets à court-terme (1 semaine) et long-terme (3 mois) de trois médicaments ciblant ces systèmes biologiques, sur les dysfonctions cardiovasculaires observées dans un modèle d’ICFEp associée au SM, le rat Zucker fa/fa. Ainsi nous avons utilisé un antagoniste des récepteurs de l’endothéline, le macitentan, un antagoniste du récepteur minéralocorticoide, la finérénone, ainsi que d’une molécule diminuant la dysfonction mitochondriale, l’iméglimine. Dans les trois études à court-terme nous avons retrouvé une amélioration de la dysfonction diastolique, une augmentation de la perfusion cardiaque ainsi qu’une restauration de la relaxation coronaire endothélium dépendante. Ces améliorations étaient associées à une diminution de la production d’espèces réactives de l’oxygène au niveau du ventricule gauche. Dans les trois études à long-terme nous avons obtenus les mêmes résultats sur les fonctions vasculaire et cardiaque avec au niveau structurel une diminution du collagène interstitiel cardiaque. La production d’espèces réactives de l’oxygène était également diminuée avec les trois traitements Cette étude montre que, dans un modèle d’ICFEp associée au SM, le blocage des récepteurs de l’endothéline ou du récepteur minéralocorticoide, ou la prévention de la dysfonction mitochondriale permettent d’améliorer les dysfonctions cardiaque et vasculaire probablement via une diminution du stress oxydant / Metabolic Syndrome (MS) is associated with an increase in cardiovascular adverse events and specifically with heart failure with preserved ejection fraction (HFpEF). HFpEF represents up to 50% of HF however, no treatment effective on mortality has been yet identified. MS related-HFpEF is a multifactorial syndrome in which an increase in endothelin signaling, in mineralocorticoid receptor activation as well as mitochondria dysfunction is found and participate to the pathology. The present goal of the thesis was to evaluate in three different projects the effects of short- (1 week) and long-term (3 months) treatments, each targeting one of these biological systems, on cardiovascular dysfunction observed in a rat model of MS associated HFpEF. We have chosen the endothelin receptors antagonist macitentan, the mineralocorticoid receptor antagonist finerenone and the new glucose-lowering agent imeglimin. Our results clearly show after the short-term studies an improvement in diastolic dysfunction, an increase in myocardial perfusion as well as restoration of endothelium-dependent coronary relaxation with the 3 treatments. All these improvements were associated with a decrease in left ventricular (LV) reactive oxygen species production (ROS). We obtained the same results after the long-term studies with a decrease in LV interstitial collagen deposition. ROS production was also decreased with the 3 components. This study clearly shows that in a rat model of MS related-HFpEF, blocking endothelin receptors or mineralocorticoid receptors as well as preventing mitochondrial dysfunction is associated with an improvement in cardiac and vascular dysfunctions. These improvements probably involve, among other mechanisms, a decrease in oxidative stress.

Introduktion: Vänsterkammarens ejektionsfraktion (VKEF) är ett central mått på systolisk funktion i vänster kammare och är en av de mest betydelsefulla parametrar vid ekokardiografiska undersökningar. Idag är Simpson biplan metoden den mest använda metoden för bestämning av ejektionsfraktionen. Vid ekokardiografiska undersökningar sänder givaren med piezoelektriska kristaller ut ultraljudsvågor med en frekvens över 20 000 Hz. Ljudvågorna som skickas ut i kroppen reflekteras och sedan återvänder de till givaren för att skapa en bild. Denna studie jämför den tvådimensionella (2D) ultraljudsmetoden Simpsons biplan med Philips Heart Model som är en automatiserad tredimensionella (3D) funktion för bedömning av VKEF.  Material och metod: I studien inkluderades 31 hjärtfriska försökspersoner mellan åldrarna 21-64. Det samlades in bilder på apikala 4- och 2 kammarbilder från alla försökspersoner där Simpsons biplan metoden användes för att beräkna ejektionsfraktion. Apikala 4-kammarbilder samlades in för att beräkna ejektionsfraktionen med Philips Heart Model 3D funktion.  Resultat: Resultatet från denna studie visade att det inte föreligger någon signifikant skillnad mellan Simpsons biplan metoden och Philips Heart Model metoden för bestämning av ejektionsfraktion. Båda metoderna visade likvärdiga mätresultat.  Diskussion: Philips Heart Model metoden är en relativ ny funktion som använder sig av artificiell intelligens för att analysera 3D bilder. Philips Heart Model metoden är en säker funktion att använda då de flesta studier bevisar likvärdiga och säkra mätresultat i jämförelse med andra metoder.  Konklusion: Enligt denna studie ger Philips Heart Model funktionen likvärdiga mätresultat av vänsterkammarens ejektionsfraktion i jämförelse med Simpsons biplan. / Introduction: Simpson’s biplane method is the most used method for determining the left ventricular ejection fraction (LVEF) in echocardiographic examinations. Ejection fraction is a central measurement of the heart's global systolic function. The probe with piezoelectric crystals emits ultrasound waves with a frequency above 20,000 Hz. The sound waves that are sent out into the body are reflected and then return to the probe to create an image. This study compares the two-dimensional (2D) ultrasound Simpson's biplane method with the Philips Heart Model method, which is an automated three-dimensional (3D) function for assessment of LVEF.                                                                                                                          Material and method: 31 subjects with no recorded heart pathologies between the ages of 21-64 were included in the study. Apical 4- and 2-chamber images were collected from the test subjects, where the Simpson's biplane method was applied to calculate the ejection fraction. 2D apical 4-chamber images were collected to convert to 3D and used to calculate the ejection fraction with the Philips Heart Model.    Results: The results of this study showed that there is no significant difference between the Simpson’s biplane method and the Philips Heart Model method for determining ejection fraction.    Discussion: The Philips Heart Model method is a relatively new feature that uses artificial intelligence to analyze 3D images. The Philips Heart Model method is a reliable feature to use as most studies have proven similar and reliable measurements when comparing it with other methods for determining LVEF.    Conclusion: According to this study, the Philips Heart Model feature provides equivalent measurements in comparison with the manual method Simpson's biplane.