Studies of the gastro-oesophageal junction in normal and overweight healthy volunteers

Introduction: Oesophageal adenocarcinoma has increased dramatically in incidence over the past three decades with a particularly high burden of disease at the gastro-oesophageal junction. Many cases occur in individuals without known gastro-oesophageal reflux disease and in the absence of Barrett’s oesophagus suggesting that mechanisms other than traditional reflux may be important. Distal squamous mucosa may be prone to acid damage even in the absence of traditional reflux by the mechanism of distal opening of the lower oesophageal sphincter. This is splaying of the distal segment of lower oesophageal sphincter allowing acid ingress without traditional reflux. It has been suggested that the cardiac mucosa at the gastro-oesophageal junction, separating oesophageal squamous mucosa and acid secreting columnar mucosa of the stomach may be an abnormal mucosa arising as a consequence of acid damage. By this theory the cardiac mucosa is metaplastic and akin to ultra-short Barrett’s oesophagus. Obesity is a known risk factor for adenocarcinoma at the gastro-oesophageal junction and its rise has paralleled that of oesophageal cancer. Some of this excess risk undoubtedly operates through stress on the gastro-oesophageal junction and a predisposition to reflux. However we sought to explore the impact of obesity on the gastro-oesophageal junction in healthy volunteers without reflux and in particular to determine the characteristics of the cardiac mucosa and mechanisms of reflux in this group. Methods: 61 healthy volunteers with normal and increased waist circumference were recruited. 15 were found to have a hiatus hernia during the study protocol and were analysed separately. Volunteers had comprehensive pathological, physiological and anatomical assessments of the gastro-oesophageal junction including endoscopy with biopsies, MRI scanning before and after a standardised meal, prolonged recording of pH and manometry before and after a meal and screening by fluoroscopy to identify the squamo-columnar junction. In the course of the early manometric assessments a potential error associated with the manometry system recordings was identified. We therefore also sought to document and address this on the benchtop and in vivo. Key Findings: 1. In documenting the behaviour of the manoscan we described an immediate effect of temperature change on the pressure recorded by the sensors; ‘thermal effect’ and an ongoing drift of the recorded pressure with time; ‘baseline drift’. Thermal effect was well compensated within the standard operation of the system but baseline drift not addressed. Applying a linear correction to recorded data substantially reduced the error associated with baseline drift. 2. In asymptomatic healthy volunteers there was lengthening of the cardiac mucosa in association with central obesity and age. Furthermore, the cardiac mucosa in healthy volunteers demonstrated an almost identical immunophenotype to non-IM Barrett’s mucosa, which is considered to arise by metaplasia of oesophageal squamous mucosa. These findings support the hypothesis that the cardia is metaplastic in origin. 3. We have demonstrated a plausible mechanism of damage to distal squamous mucosa in association with obesity. In those with a large waist circumference we observed increased ingress of acid within but not across the lower oesophageal sphincter; ‘intrasphincteric reflux’ 4. The 15 healthy volunteers with a hiatus hernia were compared to 15 controls matched for age, gender and waist circumference. Those with a hiatus hernia had a longer cardiac mucosa and although they did not have excess traditional reflux they had excess distal acid exposure by short segment acid reflux and intrasphincteric acid reflux. Conclusions: These findings are likely to be relevant to adenocarcinoma of the gastro-oesophageal junction

Orchidaceæ: illustrations and studies of the family Orchidaceæ.

Fascicle 1, by Oakes Ames.

Modelling and studies of the spectral response of some optoelectronic components

Solar radiation takes in today's world, an increasing importance. Different devices are used to carry out spectral and integrated measurements of solar radiation. Thus the sensors can be divided into the fallow types: Calorimetric, Thermomechanical, Thermoelectric and Photoelectric. The first three categories are based on components converting the radiation to temperature (or heat) and then into electrical quantity. On the other hand, the photoelectric sensors are based on semiconductor or optoelectronic elements that when irradiated change their impedance or generate a measurable electric signal. The response function of the sensor element depends not only on the intensity of the radiation but also on its wavelengths. The radiation sensors most widely used fit in the first categories, but thanks to the reduction in manufacturing costs and to the increased integration of electronic systems, the use of the photoelectric-type sensors became more interesting. In this work we present a study of the behavior of different optoelectronic sensor elements. It is intended to verify the static response of the elements to the incident radiation. We study the optoelectronic elements using mathematical models that best fit their response as a function of wavelength. As an input to the model, the solar radiation values are generated with a radiative transfer model. We present a modeling of the spectral response sensors of other types in order to compare the behavior of optoelectronic elements with other sensors currently in use.

Preclinical studies of the combined effect of anti-MYCN PNA and Retinoic Acid as potential approach to treat Neuroblastoma

Neuroblastoma (NB) is the deadliest cancer in early childhood. Around 25% of patients pre- sent MYCN-amplification (MNA) which is linked to poor prognosis, metastasis, and therapy- resistance. While retinoic acid (RA) is beneficial only for some NB patients, the cause of its resistance is still unknown. Thus, there remains a need for new therapies to treat NB. I show that MYCN-specific inhibition by the antigene oligonucleotide BGA002 in combination with 13-cis RA (BGA002-RA) overcome resistance in MNA-NB cell lines, leading to potent MYCN mRNA expression and protein decrease. Moreover, BGA002-RA reactivated neuron differentiation or led to apoptosis in MNA-NB cell lines, and inhibited invasiveness capacity. Since NB and PI3K/mTOR pathway are strictly related MYCN down-regulation by BGA002 led to mTOR pathway inhibition in MNA-NB, that was strengthened by BGA002-RA. I further analyzed if MYCN silencing may induce autophagy reactivation, and indeed BGA002-RA caused a massive increase in lysosomes and macrovacuoles in MNA-NB cells. In addition, while MYCN is known to induce angiogenesis, BGA002-RA in vivo treatment elim- inated the tumor vascularization in a MNA-NB mice model, and significantly increased the survival. Overall, these results indicate that MYCN modulation mediates the therapeutic efficacy of RA and the development of RA resistance in MNA-NB. Furthermore, by targeting MYCN, we show a cancer-specific way of mTOR pathway inhibition only in MNA-NB, avoiding side effects of targeting mTOR in normal cells. These findings warrant clinical testing of BGA002-RA as a potential strategy to overcome RA resistance in MNA-NB.

GEANT4 Radioprotection studies of the ERHA system for protontherapy treatment

This work is focused on the radiation protection for a protontherapy facility. The aim is to simulate with the best accuracy the prompt radiation field of the proton accelerator situed in Ruvo di Puglia, owned by Linearbeam s.r.l. company. In order to simulate it, is used Geant4, a software for interaction simulations of particles with matter. Thanks to internship work, thesis speaks about cancer therapy with a new method for particle acceleration, a linear beam. For a complete overview of the therapy, this work starts with a crush course on interactions of particle with matter, goes specifically to biological matter, then is shown a brief introduction to shielding studies for a particle acceleration facility, and then a presentation of Geant4. At the end, the main aspects of the proton accelerator are simulated, from proton hitting material of beam-pipe to detectors used to measure dose.

Uma análise dialógica de crônicas de Josué Machado: discursos em conflito

This coursework aims the dialogical analysis of discourses that constitute the statements given by Josué Machado, a journalist in the magazine Língua Portuguesa, publishing Segmento. The research aims to observe the ideologies that mark the statements in question, regarding to the values of the standard language and the quality of a text. Methodologically, we seek the understanding of how the discourse of analyzed chronic , publicized during the stated period from number 32 to number 70, dialogues with purist discourse and the discourse of sociolinguistics. The methodological theoretical support covers Bakhtinian studies of the discourse. The results show that the subject who enunciates in the analyzed chronicles shows in his speech a purist voice, in which the discourse of clarity takes emphasis. The values that define his discourse about language are those that prevail in the sphere of journalism

O discurso sobre a produção textual de gêneros literários

This paper aims to discuss teaching of literary genres writing. It presents reflections on studies of teaching of writing and on official documents that define pedagogical practices of text production. It presents, finally, a discourse analysis of the production of literary genres in Revista Língua Portuguesa, showing how is the media coverage of the teaching of writing in this vehicle. The research is based on Bakhtin studies of discourse.

Clarice Lispector - the hour of the star: the speech in the exhibition pamphlet

This work attempts to discuss, in the light of the French Analysis of the Discourse, how the concept of memory and heterogeneity in language actions can contribute to a reflection on information and documentation studies. Starting from cuttings of Clarice Lispector - the hour of the star exhibition pamphlet, accomplished in the second semester of 2007 by the Portuguese Language Museum (Luz train station, Sao Paulo), we interpreted the several voices that surround and sustain the subject and the sense.

Solid-phase synthesis and NMR studies of modified oligonucleotides forming triplex helix and of oligonucleopeptides mimicking the topoisomerase I-DNA covalent complex

Report for the scientific sojourn carried out at the Institut de Biologia Molecular de Barcelona of the CSIC –state agency – from april until september 2007. Topoisomerase I is an essential nuclear enzyme that modulates the topological status of DNA, facilitating DNA helix unwinding during replication and transcription. We have prepared the oligonucleotide-peptide conjugate Ac-NLeu-Asn-Tyr(p-3’TTCAGAAGC5’)-LeuC-CONH-(CH2)6-OH as model compound for NMR studies of the Topoisomerase I- DNA complex. Special attention was made on the synthetic aspects for the preparation of this challenging compound especially solid supports and protecting groups. The desired peptide was obtained although we did not achieve the amount of the conjugate needed for NMR studies. Most probably the low yield is due to the intrinsic sensitive to hydrolysis of the phosphate bond between oligonucleotide and tyrosine. We have started the synthesis and the structural characterization of oligonucleotides carrying intercalating compounds. At the present state we have obtained model duplex and quadruplex sequences modified with acridine and NMR studies are underway. In addition to this project we have successfully resolved the structure of a fusion peptide derived from hepatitis C virus envelope synthesized by the group of Dr. Haro and we have synthesized and started the characterization of a modified G-quadruplex.

Studies of Eu- and Yb-induced Reconstructions on the Si(100) Surface

This thesis presents experimental studies of rare earth (RE) metal induced structures on Si(100) surfaces. Two divalent RE metal adsorbates, Eu and Yb, are investigated on nominally flat Si(100) and on vicinal, stepped Si(100) substrates. Several experimental methods have been applied, including scanning tunneling microscopy/spectroscopy (STM/STS), low energy electron diffraction (LEED), synchrotron radiation photoelectron spectroscopy (SR-PES), Auger electron spectroscopy (AES), thermal desorption spectroscopy (TDS), and work function change measurements (Δφ). Two stages can be distinguished in the initial growth of the RE/Si interface: the formation of a two-dimensional (2D) adsorbed layer at submonolayer coverage and the growth of a three-dimensional (3D) silicide phase at higher coverage. The 2D phase is studied for both adsorbates in order to discover whether they produce common reconstructions or reconstructions common to the other RE metals. For studies of the 3D phase Yb is chosen due to its ability to crystallize in a hexagonal AlB2 type lattice, which is the structure of RE silicide nanowires, therefore allowing for the possibility of the growth of one-dimensional (1D) wires. It is found that despite their similar electronic configuration, Eu and Yb do not form similar 2D reconstructions on Si(100). Instead, a wealth of 2D structures is observed and atomic models are proposed for the 2×3-type reconstructions. In addition, adsorbate induced modifications on surface morphology and orientational symmetry are observed. The formation of the Yb silicide phase follows the Stranski-Krastanov growth mode. Nanowires with the hexagonal lattice are observed on the flat Si(100) substrate, and moreover, an unexpectedly large variety of growth directions are revealed. On the vicinal substrate the growth of the silicide phase as 3D islands and wires depends drastically on the growth conditions. The conditions under which wires with high aspect ratio and single orientation parallel to the step edges can be formed are demonstrated.

The Discourse of Home Recording : Accessibility, Exclusion and Power

Ce mémoire propose une analyse critique du discours de l’enregistrement sonore à domicile (home recording). Dans la foulée des propos mettant de l’avant l’ «accessibilité» et la «démocratisation» de l’enregistrement sonore, ce mémoire analyse les relations de savoir/pouvoir produites et légitimées par le discours, ce qu’elles permettent et contraignent, autorisent et excluent. Le corpus à l’étude est issu de la presse musicale ainsi que de forums de discussion en ligne relevant de sites spécialisés. Les méthodes utilisées sont inspirées de l’approche du discours développées par Michel Foucault et de ce que Johnson et. al. (2004) appellent l’interprétation critique. L’analyse met en évidence les deux principaux sujets du discours de l’enregistrement sonore à la maison : les professionnels de l’enregistrement et les «pros» de l’enregistrement à domicile, deux groupes constitués d’hommes financièrement aisés. Les règles qui régissent l’enregistrement à domicile semblent reprendre, en les adaptant, celles régissant les studios professionnels. Ce mémoire suggère que la «démocratisation» telle qu'énoncée dans ce discours articule l'«accessibilité contemporaine» à certains savoirs et certaines technologies à des exclusions singulières – comme des femmes et des personnes de moyens limités – qui rendent ce discours possible. Être dans le vrai, dans ce discours, c’est échanger, argumenter, discuter et prescrire des façons de faire et de dire qui font des studios professionnels l’espace des normes et des légitimités. Mots clés: enregistrement, musique, maison, domicile, studio, démocratisation, technologie, l'analyse du discours, relations de pouvoir/savoir, Michel Foucault.

Hydrometeorological Studies of Kerala state in relation to the Western Ghats

Study of Kerala State in relation to the western Ghats, using The present thesis envisages a hydrometeorological various statistical techniques and the water balance concepts first developed by Thornthwaite. The first chapter of the thesis gives general introduction where the purpose and scope of the study have been given. Chapter II discusses the importance of hydrometeorological studies in general and of water balance in particular, in planning for the overall development of any region. Chapter III consists of the presentation of various geographical features of Kerala. An introduction to the physiography of the western Ghats and detailed hydroclimatic studies of the Western Ghats region which includes analysis of rainfall and the study of water balance elements form Chapter IV. In Chapter V, a detailed hydrometeorological study of Kerala State is made. Discussion of the results of the study and suggestions for optimum utilization of the available water resources for the overall development of the western Ghats region in general and Kerala in particular are made in Chapter VI.

Studies On The Biology And Fishery Of The Fishes Of The Family Priacanthidae (Pisces : Perciformes) Of Indian Waters

Preliminary investigations revealed that 3. hamrur is the predominant species along the east and west coasts of India while other species are sparsely distributed and occur sporadically. In the present investigation, aspects such as population parameters, breeding and feeding biology, fishery etc. of _l:. hamrur of the north east coast of India (Fig.1) are dealt with. Studies on the distribution, abundance and stock size of priacanthids all along the Indian waters were undertaken. Taxonomic studies of the priacanthid species encountered during the study from the Indian waters is also attempted

Estudios sonoros desde la Región Andina UIO-BOG = Sonic Studies from the Andean Region

El presente trabajo se basa en el análisis de las prácticas sonoras y, a partir de ahí, de una apuesta por un nuevo campo de estudios, el de los Estudios Sonoros; cuyo fin último es establecer una perspectiva epistemológica y política de las prácticas experimentales con sonido, en diálogo con proyectos provenientes de los Estudios Culturales, como son el proyecto modernidad/ colonialidad, las teorías poscoloniales y los estudios subalternos. Desde estas posiciones teóricas y políticas, estoy conciente de que el sonido, y sus posibilidades experimentales, articulan un régimen influyente en el mundo contemporáneo. Razón por la cual, sobre todo, esta es una reflexión desde las prácticas sonoras que surgen en dos ciudades andinas: Quito y Bogotá, como una expresión emergente para establecer encuentros Sur-Sur, que puedan generar diálogos epistemológicos sobre el sonido. En otras palabras, en este libro estoy proponiéndo a mis lectoras y lectores, una especie de “juego epistémico”: comprender el sonido como un lugar de conocimiento.Y el sonido es conocimiento precisamente porque el sonido nos permite vernos (y permite verme) como un sujeto históricamente ubicado. En el capítulo primero abordaré la pregunta de cómo se fue articulando el régimen discursivo del sonido como arte, dentro de diálogos y conflictos que se generaron en el contexto de la Guerra Fría que, para el caso de Latinoamérica, constituyó la transferencia de conocimientos articulados desde promesas como el desarrollismo y la modernización. También analizaré el cómo se configuraron, tanto en Quito como en Bogotá, las nuevas subjetividades “artísticas” frente al discurso de las vanguardias europeas del siglo XX y el experimentalismo estadounidense. Como verán mis lectoras y lectores, estos modelos, aparentemente originales e innovadores, fueron influidos por formas de saber y poder moduladas alrededor de la idea de la renovación de las artes a través del sonido, formulación que instaló el sonido como dispositivo/materia desde el cual, en detrimento de lo local, se articuló la fantasía de un universal deseado: las máquinas de sonido y de reproducibilidad técnica. En el segundo capítulo me centraré en algunas prácticas de experimentación sonora para indagar cuestiones como el estilo, procedimiento posmodernista ampliamente diseminado dentro de las instituciones artísticas y de éstas hacia la vida cotidiana. A partir de lo cual intentamos esclarecer el porqué de la confiscación y sometimiento de lo sonoro bajo el cuidadoso encierro del régimen discursivo del arte, que de manera eficiente lo absorbe como un “nuevo” medio para disciplinarlo y nombrarlo como proyecto sonoro, pieza sonora, instalación sonora, performance sonoro, acción sonora, objeto sonoro, paisaje sonoro, composición, loop. En otras palabras, cómo todo lo que genera el posmodernismo es apropiado por las universidades para crear la noción de “pastiche”, en donde todo cabe, bajo la indulgencia del “estilo”, procedimiento desde el cual se va instalando el régimen de verdad de un nuevo universal deseado: El Arte Sonoro. En este mismo capítulo, indagamos sobre las lógicas de producción de estas prácticas, para avanzar hacia las lógicas culturales donde lo sonoro se define y redefine por el posicionamiento y el lugar desde el que actúan los sujetos. Bajo estas consideraciones, queda planteada la propuesta, acuñada por esta investigación, la de un nuevo campo de estudio: Los Estudios Sonoros, propuesta que debe ser entendida como lo que algunos intelectuales latinoamericanos llaman epistemes emergentes11, precisamente porque esta investigación hace un esfuerzo por esclarecer las interdependencias existentes entre prácticas artísticas con sonido, el campo discursivo del arte y otras construcciones discursivas de la modernidad-colonialidad que establecen y regulan la formación del régimen sonoro. En el capítulo tercero analizaré cómo un “medio de creación” se vuelve hegemónico y cómo ciertos artistas que usan el sonido, bajo la pretensión de representar la marginalidad, marginalizan aún más a las personas que han sido históricamente subalternizadas. Seguido de este análisis, en el capítulo cuarto, indagamos sobre las tácticas que marcan nuevas formas de adhesión, de representación y de resistencia cultural, las mismas que son estrategias suplementarias frente, y en contra, de los discursos dominantes de las prácticas artísticas con sonido y las geopolíticas de conocimiento.

Investigation of the prototype silylene reaction, SiH2+H2O(and D2O): time-resolved gas-phase kinetic studies, isotope effects, RRKM calculations, and quantum chemical calculations of the reaction energy surface

Time-resolved kinetic studies of the reaction of silylene, SiH2, with H2O and with D2O have been carried out in the gas phase at 296 and at 339 K, using laser flash photolysis to generate and monitor SiH2. The reaction was studied over the pressure range 10-200 Torr with SF6 as bath gas. The second-order rate constants obtained were pressure dependent, indicating that the reaction is a third-body assisted association process. Rate constants at 339 K were about half those at 296 K. Isotope effects, k(H)/k(D), were small averaging 1.076 0.080, suggesting no involvement of H- (or D-) atom transfer in the rate determining step. RRKM modeling was undertaken based on a transition state appropriate to formation of the expected zwitterionic donoracceptor complex, H2Si...OH2. Because the reaction is close to the low pressure (third order) region, it is difficult to be definitive about the activated complex structure. Various structures were tried, both with and without the incorporation of rotational modes, leading to values for the high-pressure limiting (i.e., true secondorder) rate constant in the range 9.5 x 10(-11) to 5 x 10(-10) cm(3) molecule' s(-1). The RRKM modeling and mechanistic interpretation is supported by ab initio quantum calculations carried out at the G2 and G3 levels. The results are compared and contrasted with the previous studies.