Dissertations / Theses on the topic 'Organs'

The Bionic Ear is properly called a cochlear implant. It is an artificial hearing tool which stimulates nerves, using electricity, in the inner ear. The Bionic Ear helps a deaf person to hear another person speak. When you are citing the document, use the following link http://essuir.sumdu.edu.ua/handle/123456789/33760

Reconstructed tomographic image resolution of small animal PET imaging systems is improving with advances in radiation detector development. However the trend towards higher resolution systems has come with an increase in price and system complexity. Recent developments in the area of solid-state photomultiplication devices like silicon photomultiplier arrays (SPMA) are creating opportunities for new high performance tools for PET scanner design. Imaging of excised small animal organs and tissues has been used as part of post-mortem studies in order to gain detailed, high-resolution anatomical information on sacrificed animals. However, this kind of ex-vivo specimen imaging has largely been limited to ultra-high resolution μCT. The inherent limitations to PET resolution have, to date, excluded PET imaging from these ex-vivo imaging studies. In this work, we leverage the diminishing physical size of current generation SPMA designs to create a very small, simple, and high-resolution prototype detector system targeting ex-vivo tomographic imaging of small animal organs and tissues. We investigate sensitivity, spatial resolution, and the reconstructed image quality of a prototype small animal PET scanner designed specifically for imaging of excised murine tissue and organs. We aim to demonstrate that a cost-effective silicon photomultiplier (SiPM) array based design with thin crystals (2 mm) to minimize depth of interaction errors might be able to achieve sub-millimeter resolution. We hypothesize that the substantial decrease in sensitivity associated with the thin crystals can be compensated for with increased solid angle detection, longer acquisitions, higher activity and wider acceptance energy windows (due to minimal scatter from excised organs). The constructed system has a functional field of view (FoV) of 40 mm diameter, which is adequate for most small animal specimen studies. We perform both analytical (3D-FBP) and iterative (ML-EM) methods in order to reconstruct tomographic images. Results demonstrate good agreement between the simulation and the prototype. Our detector system with pixelated crystals is able to separate small objects as close as 1.25 mm apart, whereas spatial resolution converges to the theoretical limit of 1.6 mm (half the size of the smallest detecting element), which is to comparable to the spatial resolution of the existing commercial small animal PET systems. Better system spatial resolution is achievable with new generation SiPM detector boards with 1 mm x 1 mm cell dimensions. We demonstrate through Monte Carlo simulations that it is possible to achieve sub-millimeter spatial image resolution (0.7 mm for our scanner) in complex objects using monolithic crystals and exploiting the light-sharing mechanism among the neighboring detector cells. Results also suggest that scanner (or object) rotation minimizes artifacts arising from poor angular sampling, which is even more significant in smaller PET designs as the gaps between the sensitive regions of the detector have a more exaggerated effect on the overall reconstructed image quality when the design is more compact. Sensitivity of the system, on the other hand, can be doubled by adding two additional detector heads resulting in a, fully closed, 4π geometry.

Le pourcentage élevé de blessures dues à des traumatismes abdominaux survenant lors d’accidents de la route mais également la nécessité de détecter des maladies (l'hépatite virale, la cirrhose, le cancer etc.), ont conduits plusieurs chercheurs à étudier les propriétés mécaniques des organes abdominaux à la fois in vivo et in vitro. Dans tous les MEF de corps humain actuellement disponibles, les organes abdominaux sont caractérisés par des lois élastiques linéaires ou viscoélastiques linéaires, alors que ces matériaux montrent un comportement non linéaire hyper élastique. L’objectif de ce travail de thèse est de développer des modèles par éléments finis (MEF) robustes des différents organes de l’abdomen tels que le foie, le rein et la rate. Pour ce faire des tests expérimentaux sur chacun des constituants de ces organes ont été réalisés dans le but de caractériser le comportement mécanique de ceux-ci et de déterminer les propriétés mécaniques inhérentes à ces constituants. Pour caractériser mécaniquement ces différents constituants, des tests statiques ont donc été réalisés pour chacun des constituants du foie et du rein porcin à savoir, des tests de traction de la capsule de Glisson et de la capsule rénale ainsi que des veines hépatiques, des tests de compression et de cisaillement pour le parenchyme hépatique et le cortex rénale. Finalement la rate a été testée en compression statique. Les résultats expérimentaux obtenus ont été utilisés afin de caractériser les tissus par des lois de comportement de type hyper élastique, viscoélastique et hyper viscoélastique sous la forme de modèles d'Ogden, Mooney Rivlin et Maxwell et implémentés dans les MEF porcin et humain développés dans le cadre de cette thèse. Ces MEF ont ensuite été validés en regards de tests expérimentaux dynamiques in vivo réalisés sur modèle porcin et vis-à-vis de la littérature pour les MEF d’organes humains. Ainsi, les MEF développés dans cette étude sont les premiers modèles détaillés et validés et peuvent désormais être utilisés dans le cadre de reconstructions d’accidents mais également pour des applications biomédicales dans le but de développer des environnements virtuels de chirurgie, de planifier les actes chirurgicaux et d’aider les chirurgiens à l’apprentissage de gestes
The objective of this study is to develop robust finite element models of abdominal organs (viz. liver, kidney and spleen), by performing experiments on each organ’s constituents to extract the material properties. Understanding the mechanical properties of the organs of the human body is the most critical aspect of numerical modeling for medical applications and impact biomechanics. Many researchers work on identifying mechanical properties of these organs both in vivo and in vitro considering the high injury percentage of abdominal trauma in vehicle accidents and for easy detection of diseases such as viral hepatitis, cirrhosis, cancer etc. In all the current available finite element human body models the abdominal organs are characterized as linear elastic or linear visco-elastic material, where as the materials actually show a non linear hyper elastic behavior. In this study the organs are modeled for first time as hyper visco-elastic materials and with individual constituents of each (viz. the capsule and veins). To characterize the tissue, static experiments are performed on individual parts of the abdominal organs, like incase of liver, Glisson’s capsule and hepatic veins are tested under static tension where as liver parenchyma is tested under static compression and under shear at low frequency. In case of kidneys, renal capsule is tested under static tension and renal cortex is tested under static compression, where as spleen tissue is tested under static compression. The results of the these experiments are used to characterize the tissues as hyper elastic, visco elastic and hyper visco elastic materials in the form of Ogden, Mooney Rivlin and Maxwell materials. These material models are further used to develop the finite element model of organs for human and pigs. The developed models are validated by performing in vivo dynamic tests on pigs, whereas using dynamic tests data from the literature on human liver and reproducing the same with the numerical approach in the LS Dyna explicit solver. The developed models are observed to be robust and can be used for accident reconstruction as well for biomedical applications viz., to develop virtual surgical environments & to plan surgeries or train surgeons

Made available in DSpace on 2016-08-03T12:30:39Z (GMT). No. of bitstreams: 1 Paulo Carvalho.pdf: 443562 bytes, checksum: 968b1d8d0b3dd7e3e67d2ccf449290e0 (MD5) Previous issue date: 2007-12-14
This objective of the project is to provide an explanation for the use of Internal Communication in Brazil through house-organs. In order that, I used two main research resources: the published bibliography on this theme and the Premio Aberje winners of the last 7 (seven) years. Tthe goal is to verify, on one side, what the authors and experts write and point out the best way to create an Internal Communication flow through house-organs; on the other side, the focus is to analyze this theory and establish what is to do in practice. The selection of the Premio Aberje winners House-organ category to Internal Communication has the goal on to show one logical criteria for selecting media representatives of Organizacional Communication área in Brazil. The focus of the project is to analyze the content of these vehicles and their coverage such as organizational speech flow, messages, the kind of the language etc. Aspects of the page layout and design are not the goal.(AU)
Este projeto tem como objetivo realizar uma análise da forma com que vem sendo realizada, na prática, a Comunicação Interna no Brasil por meio de house-organs. Para tanto, utiliza-se de duas fontes principais de consulta: a bibliografia publicada sobre o tema e os vencedores do Prêmio Aberje dos últimos 7 (sete) anos. Com isso, pretende-se verificar, de um lado, o que autores e especialistas sugerem e indicam como ideal para execução da Comunicação Interna através de house-organs; de outro, analisa-se, com base nessa teoria, o que vem sendo feito na prática. A escolha dos vencedores do prêmio Aberje categoria House-organ para Comunicação Interna, tem como objetivo apenas apresentar um critério lógico para a seleção das mídias analisadas, uma vez que se trata de um prêmio concedido pelo principal órgão de representação da Comunicação Empresarial do Brasil. O foco deste estudo é exclusivamente o conteúdo dos veículos e neste se encaixam itens como o fluxo do discurso organizacional (ascendente, descendente etc.), mensagens, o tipo de linguagem utilizada etc. Não se focarão, dessa maneira, aspectos de diagramação e estética.(AU)

Das herkömmliche völkerrechtliche Institut des diplomatischen Schutzes ist im Verhältnis zwischen Staaten (als originären Völkerrechtssubjekten) entstanden. Aber auch intergouvernmentale Organisationen sind in der Lage, Maßnahmen mit unmittelbarer Rechtswirkung gegenüber Einzelpersonen zu treffen, so daß auch hier die Frage aufzuwerfen ist, wann und mit welchen Mitteln der jeweilige Heimatstaat die (Grund-)Rechte seiner Staatsangehörigen gegenüber einer solchen Organisation geltend machen kann.

Organs of state shall terminate the procurement contracts if it is found that there were irregularities and concluded in contravention of the applicable legislation.1 The general rule is that a contract which has been concluded in violation of legislation is void.2 Section 2 of the Constitution of the Republic of South Africa, 1996 states that law or conduct inconsistent with the Constitution is invalid. When organs of state procure goods or services they are exercising public power of which they are subject to the provisions of the Constitution which is the supreme law. Organs of state which fail to heed the provisions of the procurement laws and or a policy will be acting unlawfully and their decisions will be attack3 as they will be in conflict with the rule of law and the principle of legality.4
Mini Dissertation (LLM)--University of Pretoria, 2018.
Mercantile Law
LLM
Unrestricted

Kyoto University (京都大学)
0048
新制・課程博士
博士(農学)
甲第10233号
農博第1305号
新制||農||862(附属図書館)
学位論文||H15||N3754(農学部図書室)
UT51-2003-H654
京都大学大学院農学研究科応用生命科学専攻
(主査)教授 永尾 雅哉, 教授 伏木 亨, 教授 吉川 正明
学位規則第4条第1項該当

Kyoto University (京都大学)
0048
新制・課程博士
博士(農学)
甲第19043号
農博第2121号
新制||農||1032(附属図書館)
学位論文||H27||N4925(農学部図書室)
31994
京都大学大学院農学研究科地域環境科学専攻
(主査)教授 縄田 栄治, 教授 田中 千尋, 教授 北島 宣
学位規則第4条第1項該当

The intertidal mussels. Perna perna and Choromytilus meridionalis co-occur on the southern coast of South Africa. Mussels ingest mixtures of bacteria. phytoplankton. zooplankton and detritus. with proportions varying according to availability. These bivalves filter similar-sized particles. which might result in interspecific competition. Carbohydrate-digesting enzymes of the mussels and their enteric bacteria. and bacteriolytic enzymes of the mussels were therefore examined to elucidate feeding ecology in these animals at an enzymatic level. Style enzymes of both species digested the storage carbohydrates amylose glycogen and laminarin, and the structural carbohydrate carboxymethyl cellulose (CMC). Differential rates of digestion of these carbohydrates suggests that Perna perna relies more on plankton (and possibly bacteria) than on detritus for food while Choromytilus meridionalis relies equally on all components of the seston. There may therefore be some degree of resource partitioning of the seston. The styles of P.perna had a lower specific enzyme activity. but higher protein content than those of C.meridionalis. P.perna could therefore release more glucose from a given concentration of substrate than C.meridionalis. The gut contents and tissue were examined microscopically to determine where the bacterial colonisation sites were. Bacteria were associated primarily with the gut contents but not the gut walls. of both species. The styles housed spirochaete bacteria (Crislispira sp), Perna perna housed large numbers of one species. while Choromytilus meridionalis had lower numbers of two species. Levels of infection differed between species and localities. Enteric (but not style) bacteria of Perna perna and Choromytilus meridionalis always digested the same carbohydrates as the mussels as well as the structural carbohydrates mannan and fucoidan. Activity was erratic on the structural compounds, carageenin and xylan, and absent on alginic acid or inulin. Activity on the storage carbohydrates by enteric bacteria from C.meridionalis was higher than by those from P.perna. This is probably related to the larger bacterial populations housed by C.meridionalis than by P.perna. Bacteriolytic activity by the digestive enzymes of Pema perna was higher than for Choromytilus. In P.perna it was due to a combination of different enzymes one of which is a true lysozyme. C.meridionalis did not produce a true lysozyme. Enzymes produced by the mussels and their enteric bacteria allow the mussels to utilise all components of the seston. Low endogenous enzyme activity by Choromytilus meridionalis, coupled with the high activity by its enteric bacteria, suggests that they rely more on bacterial activity to meet their dietary requirements than does Perna perna. The ability of enteric bacteria to digest carbohydrates which the mussels cannot indicates that the bacteria are endosymbiotic, although the sporadic nature of activity of some of the enzymes, and the fact that bacteria are associated with the gut contents, indicates that the relationship is only incidental.

Thesis (Ph. D.) -- University of Maryland, College Park, 2005
Thesis research directed by: Chemical Engineering. Title from t.p. of PDF. Includes bibliographical references. Published by UMI Dissertation Services, Ann Arbor, Mich. Also available in paper.

The question of whether within chimera research certain human/nonhuman animal chimeras should not be created has received significant attention in the philosophical community. In this thesis I examine, from a philosophical perspective, four questions related to this topic. These are: (i) Can ‘human’ dignity be invoked as an argument against the creation of human/nonhuman animal chimeras? (ii) Is it morally permissible to kill human/great-ape chimeras in order to solve the human organ shortage crisis? (iii) Is there something inherently wrong with creating human/nonhuman animal chimeras capable of human gamete production and human pregnancy? (iv) Can classic animal ethics issues concerning animal welfare throw light on the issue of killing human/pig chimeras for their human organs. These four questions, in turn, fall within what have been regarded as the three main problematic cases within chimera ethics: (1) the creation of human/nonhuman animal chimeras that could have brains predominantly constituted by human brain cells; (2) the creation of human/nonhuman animal chimeras that could look human-like; (3) the creation of human/nonhuman animal chimeras capable of human gamete production and human pregnancy. In the introduction I do four things. First, I define what chimeras are and point out some problems with some of the definitions that have been proposed. Secondly, I briefly investigate if there is a sound principled objection against the intentional creation of all intraspecific and interspecific chimeras. Thirdly, I present in a detailed fashion the four questions that this thesis poses in response. Finally, I explain how the four papers that are the main body of the thesis form a coherent body of work. In the fifth section of this thesis I present the abstracts of four papers. In the sixth section I make a comprehensive exploration of the dignity-based arguments that have been advanced against the creation of human/nonhuman animal chimeras that could possess human-like mental capacities, or that could possess certain cognitive capacities that we would not be able to properly classify. In the seventh section I examine the morality of killing human/great ape chimeras for their human organs. This paper is a detailed response to Shaw et al.’s (2014) ‘Using Non-Human Primates to Benefit Humans: Research and Organ Transplantation’. The eight section covers two topics. First I discuss the moral problems related to the creation of mainly nonhuman human/nonhuman animal chimeras capable of human gamete production. Secondly, I discuss the moral problems that would be generated by the fact that a sentient nonperson human/nonhuman animal chimera, that is predominantly nonhuman, was pregnant with a human conceptus. In the ninth section I further examine the chimera welfare issues that have emerged from assessing the morality of using human/pig chimeras as human organ sources. In the conclusion of the thesis I present a summary of the main points I have explored, and proceed to present how my dissertation adds to the academic literature on chimera ethics. Finally, I present some areas for further research.

This thesis presents the application of diffusion weighted imaging (DWI) and relaxometry MRI studies in three organs in the abdomen, the kidney, colon and liver. These methods are first applied at 1.5 Tesla in healthy volunteers and patients with Cardiorenal Syndrome (CRS), a clinical condition in which cardiac and renal dysfunctions (RD) coexist. Diffusion parameters are determined using the mono-exponential ADC, bi-exponential IVIM, stretched-exponential and Kurtosis models, as well as diffusion tensor imaging (DTI) in order to assess pathophysiology and structural changes in the kidney. Complementary longitudinal relaxation time (T1) mapping and PC-MRI flow measures are collected for comparison with diffusion parameters. The assessment of the colonic content using T1 measures as a biomarker of water absorption and health is presented in the second study. The main objective of the study was to determine the robustness of bi-exponential model in the fitting of T1 in the colonic contents of ascending colon. T1 measurements of colonic content are made at different positions in the ascending colon, before and after a liquid challenge. The reliability of T1 measurements of colonic content were compared across observers. The heterogeneity in the measurements was evaluated by considering different ROI sizes and locations. The final study is the assessment of liver function associated with Chronic Liver Disease (CLD) using DWI and T1 measurement at 1.5 T and a comparison with histological measures. the Measurements of T1 and diffusion parameters (ADC and IVIM) to stratify fibrosis stage in liver disease are combined with T2* measurement of iron accumulation. The repeatability and reproducibility of this protocol is then tested in the healthy liver using MRI at 3T for the assessment of structural and haemodynamic changes for future studies, with an evaluation of the choice of b-values to inform fitting of the bi-exponential (IVIM) model provided.

Investigating how insects receive sound via the structure of their auditory organs could inspire new, more sensitive, acoustic sensor systems to be developed, where the insect hearing organs that have previously been documented are believed to be more sensitive than any man-made devices that can currently be made. Firstly though, the structure and functioning of the biological inspiration, insect tympanal hearing organs, have to be more fully understood. This Thesis research firstly investigated the biomechanical properties of the tympanal membrane of various species and orders of insect using laser Doppler vibrometry. The results were then compared between species, including the different structures and also the membrane mechanics. This chapter results highlights the different structures and also the range of frequencies that each species is tuned to. By comparing the tympanal organs shape and the mechanics on the membrane surface caused by the received sound waves hopefully this can be applied to future membrane design. Some species of insect have been found to have active hearing characteristics, in order to understand the functioning of these hearing organs these were investigated using different methods to previous studies to try and identify the origin of the active hearing. In previous studies these characteristics were recorded acoustically from the tympanal organs of a number of species. The current study aimed to record the vibration created by the emissions through the membrane this was investigated in both locust and moth tympanal organs. No active hearing characteristics were recordable on the surface of the membrane. Finally both laser vibrometry and electrophysiology recordings were used to investigate very high frequency sensitivity of a moth hearing organ. The findings have greatly extended the known range of hearing in insects. The moth hearing organ is capable of receiving and processing frequencies up to 300 kHz with a very simple tympanal organ. This discovery could inspire smaller and simpler designs of transducers at ultrasonic frequencies. Overall this thesis work demonstrates the amazing sensitivity of the insect tympanal organs and takes steps toward further understanding of the auditory processing in insect tympanal organs.

Three-dimensional (3D) bioprinting has become a fast-developing research field in the last few years. Many different technical solutions are available, with extrusion-based printing being the most promising and versatile method. In addition, a variety of biomaterials are already available for 3D printing of live cells. The real challenge, however, remains bioprinting of macroscopic, volumetric constructs of well-defined structures since hydrogels used for cell-embedding must consist of rather soft materials. This article describes recent developments to overcome these limitations that prevent clinical applications of bioprinted human tissues. New approaches include technical solutions such as in situ cross-linking or gelation processes that now can be performed during the bioprinting process, modified bioinks that combine suitable viscosity and cytocompatible gelation mechanisms, and utilization of additional materials to provide mechanical strength to the cell-laden constructs.

RIASSUNTO Le piante sono fondamentali per il mantenimento del benessere dell’umanità, in quanto forniscono numerosi servizi indispensabili per il mantenimento di un ecosistema correttamente funzionante (Whelan et al., 2005). Entro il 2050, la popolazione mondiale avrà raggiunto più o meno 9 miliardi di persone, quindi le richieste di cibo, di materie prime e di energia rinnovabile aumenteranno drasticamente (Grierson et al., 2011). Per soddisfare questa crescente domanda di beni, è necessaria una forte collaborazione interdisciplinare tra gli scienziati che lavorano per migliorare le colture e gli scienziati che si occupano dell’ambiente, in modo da tradurre specifiche conoscenze di laboratorio in soluzioni pratiche sul campo. In questo contesto, la biologia vegetale svolge un ruolo importante perché consente l'identificazione e la manipolazione di caratteri utili e interessanti che possono essere utilizzati nei programmi di breeding per selezionare nuove linee di colture con caratteristiche desiderabili come una minor necessità di input lasciando invariata la resa, e una maggior adattabilità all’ambiente. Solo lavorando in questa direzione sarà possibile arginare i problemi dell'attuale pratica agronomica come la perdita di biodiversità, il degrado del suolo, l'inquinamento chimico e l'esaurimento delle risorse idriche (Khush, 2001). In particolare, i frutti rappresentano la parte più preziosa della produzione agricola. Infatti rappresentano la parte commestibile di molte colture, comprese quelle utilizzate come frutta da dessert (mele, fragole, uva), come verdure (cetrioli, fagioli, pomodori), come fonti di oli culinari (oliva, olio di palma) o per altri prodotti culinari (vaniglia). I frutti sono importanti anche per la produzione di semi (colza, cereali) e diverse sostanze non commestibili (cotone, oli industriali) e possono essere sfruttati per la produzione di molti altri prodotti, compresi quelli farmaceutici. Da un punto di vista botanico, il frutto è il risultato dello sviluppo dell'ovario dopo l'impollinazione e la fecondazione. Questa struttura rappresenta inoltre una delle principali innovazioni evolutive di Angiosperme (Ferrandiz, 2011). Infatti, i frutti sono essenziali per la riproduzione e l'adattamento delle piante e migliorano notevolmente l'efficienza della dispersione dei semi. La capacità dei semi di germogliare e crescere lontano dalla pianta madre ha consentito alle Angiosperme di colonizzare nuove aree, riducendo il rischio di inbreeding e competizione tra sibling. Il presente lavoro può essere diviso in due diverse linee di ricerca. La prima (primo e secondo capitolo) riguarda la regolazione dell'architettura delle piante e dell'attività dei meristemi negli organismi modello Antirrhinum majus e Arabidopsis thaliana. La seconda invece (terzo e quarto capitolo) rappresenta il progetto principale di questa tesi di dottorato e mira a identificare un solido strumento per la delucidazione dei meccanismi molecolari che controllano la formazione dei frutti in Arabidopsis thaliana. Concentrandosi sulla seconda linea di ricerca, per esplorare i meccanismi che controllano la formazione e la maturazione dei frutti, abbiamo eseguito un'analisi trascrittomica sul tessuto delle valve della siliqua di Arabidopsis thaliana, utilizzando la strategia RNAseq. In tal modo, abbiamo generato un set di dati di geni differenzialmente regolati che aiuteranno a chiarire i meccanismi molecolari che sono alla base della fase iniziale della crescita del frutto, e successivamente della fase di maturazione. La robustezza del nostro set di dati è stata testata atraverso studi di genomica funzionale. Utilizzando un approccio di genetica inversa, abbiamo selezionato 10 geni differenzialmente espressi ed esplorato le conseguenze della loro distruzione sulla crescita e la senescenza delle silique. Abbiamo scoperto che i geni contenuti nel nostro set di dati (codificanti per fattori di trascrizione, proteine del citoscheletro ed enzimi che modulano l'omeostasi degli ormoni) svolgono ruoli essenziali in diversi stadi dello sviluppo e della maturazione della siliqua. Inoltre, dal nostro set di dati, tra i geni down-regolati, abbiamo trovato il gene AUXIN RESPONSE FACTOR 8 (ARF8), il cui trascritto diminuisce costantemente dal primo all'ultimo stadio di sviluppo della siliqua. ARF8 codifica per un fattore di trascrizione che può agire specificamente nel pistillo, in risposta al segnale dell’auxina. L'ormone vegetale auxina regola i principali aspetti dello sviluppo della pianta principalmente attraverso la sua distribuzione differenziale all'interno dei tessuti vegetali. In particolare, ARF8 sembra essere il legame tra il segnale ormonale e il meccanismo molecolare di formazione del frutto (Goetz et al., 2006). In Arabidopsis, la formazione del frutto viene generalmente repressa fino a quando avviene la fecondazione. Tuttavia, nel mutante auxin response factor 8-4 (arf8-4), già precedentemente caratterizzato, sembra che la formazione del frutto sia disgiunta dalla fecondazione, risultando nella formazione di un frutto privo di semi (partenocarpico; Goetz et al., 2006). La struttura che si sviluppa dal pistillo non fecondato del mutante arf8-4, è stata considerata per anni una silique partenocarpica in quanto risulta più lunga del pistillo non fecondato wild-type e presenta un pattern di deiscenza, processo essenziale per l’apertura del frutto maturo e il rilascio dei semi. Nonostante ciò, nel 2010, Carbonell-Bejerano e collaboratori hanno riferito che esiste un processo di senescenza inerente allo sviluppo che include lo sviluppo della zona di deiscenza e che risulta essere indipendente alla fecondazione. Questo processo di senescenza quindi è comune tra pistilli fecondati e non fecondati. In linea con questo studio, i nostri risultati suggeriscono che il mutante arf8-4 non presenta un vero fenotipo partenocarpico ma piuttosto mostra un’alterazione nella regolazione del cross-talk ormonale, probabilmente dovuta a una proteina tronca. Questa alterazione può a sua volta influenzare il coordinamento tra crescita e senescenza del pistillo, modificando quindi la corretta progressione dei processi di sviluppo. Per questo motivo, almeno in Arabidopsis, l'unica caratteristica strutturale che differenzia il frutto parthenocarpic di arf8-4 dal pistillo non fecondato di tipo wild-type è la dimensione aumentata. Ulteriori analisi saranno necessarie per continuare a studiare il fenotipo di arf8-4, incluse analisi molecolari ad alto rendimento (spettrometria di massa) sul contenuto di ormoni nel tessuto delle valve e analisi western-blot per confermare definitivamente la presenza della proteina tronca nelle piante mutanti arf8-4. Referenze Carbonell-Bejerano, P., Urbez, C., Carbonell, J., Granell, A. and Perez-Amador, M.A. (2010) A Fertilization-Independent Developmental Program Triggers Partial Fruit Development and Senescence Processes in Pistils of Arabidopsis. Plant Physiol., 154, 163–172. Ferrandiz, C. (2011) Fruit Structure and Diversity. Encycl. Life Sci. Goetz, M., Vivian-Smith, A., Johnson, S.D. and Koltunow, A.M. (2006) AUXIN RESPONSE FACTOR8 Is a Negative Regulator of Fruit Initiation in Arabidopsis. Plant Cell, 18, 1873–1886. Grierson, C.S., Barnes, S.R., Chase, M.W., et al. (2011) One hundred important questions facing plant science research. New Phytol., 192, 6–12. Khush, G.S. (2001) Green revolution: the way forward. Nat. Rev. Genet., 2, 815–822. Whelan, C.J., Wenny, D.G. and Marquis, R.J. (2005) Ecosystems and Human Well-being: Synthesis. Isl. Press. Washington, DC, 1–137.
ABSTRACT Plants can be consider fundamental for maintaining human well-being, since they provide several benefits that humans freely gain from the natural environment and from properly functioning ecosystems (Whelan et al., 2005). By 2050, the world population will have reached more or less 9 billion people, therefore, the demands for energy-intensive food, shelter, clothes, fibre, and renewable energy will dramatically increase (Grierson et al., 2011). To satisfy such increasing goods demand it requires a strong interdisciplinary collaboration between plant scientists, working to improve crop, and environmental scientists, working on environmental stability to translate the specific knowledge into field-based solutions. In this contest, plant developmental biology has an important role because it allow the identification and manipulation of useful and interesting traits which then can be used for breading programs to select new crop cultivars that need less inputs and are adapted to live in their environment. So they can help to overcome the problems of current agronomic practice like loss of biodiversity, soil degradation, chemical pollution and depletion of water resources (Khush, 2001). Particularly, fruit represent the most valuable part of crop production. Actually, they are the edible part of many crops, including those used as dessert fruits (apples, strawberries, grapes), as vegetables (cucumbers, beans, tomatoes), as sources of culinary oils (olive, oil palm), or for other culinary products (vanilla). Fruits are also important for seed production (canola, cereals) and several non-edible substances (cotton, industrial oils), and can be adapted to the production of many other products, including pharmaceuticals. From a botanical point of view, fruit is the result of the development of ovary after pollination and fertilization and it represent a major evolutionary innovation of Angiosperms (Ferrandiz, 2011). Actually, fruits are essential for plant reproduction and adaptation, and greatly enhance the efficiency of seed dispersal. The ability of the seeds to germinate and grow far away from the parent plant allows Angiosperms to colonize new areas, reducing the risk of inbreeding and sibling competition. The present work can be divided in two different research lines. The first one (first and second chapters) concerns the regulation of plant architecture and meristem activity in the model organisms Antirrhinum majus and Arabidopsis thaliana. The second one (third and fourth chapters) represents the main project of this PhD thesis and it aims to identify a powerful tool for the elucidation of the molecular mechanisms controlling fruit formation in Arabidopsis thaliana. Focusing on the second research line, to explore the mechanisms controlling fruit formation and maturation, we performed a transcriptomic analysis on the valve tissue of the Arabidopsis thaliana silique, using the RNAseq strategy. In doing so, we have generated a dataset of differentially regulated genes that will help to elucidate the molecular mechanisms that underpin the initial phase of fruit growth, and subsequently trigger fruit maturation. The robustness of our dataset has been tested by functional genomic studies. Using a reverse genetics approach, we selected 10 differentially expressed genes and explored the consequences of their disruption for both silique growth and senescence. We found that genes contained in our dataset (encoding for transcription factors, cytoskeletal proteins, and enzymes that modulate hormone homeostasis) play essential roles in different stages of silique development and maturation. Moreover, from our dataset, among down-regulated genes, we found the AUXIN RESPONSE FACTOR 8 (ARF8) gene, whose transcript diminishes steadily from the first time-point to the last. ARF8 encodes for a transcription factor that can act specifically in the pistil, in response to auxin signal. The plant hormone auxin regulates the major aspects of plant development mainly through its differential distribution within plant tissues. Particularly, ARF8 seems to be the link between hormone and molecular mechanism in fruit initiation (Goetz et al., 2006). In Arabidopsis, fruit initiation is generally repressed until fertilization occurs. However, in the already characterized auxin response factor 8-4 (arf8-4) mutant, it seems that fruit initiation is uncoupled from fertilization, resulting in the formation of seedless fruit (parthenocarpic fruit), if fertilization is prevented before anthesis with the removal of anthers (Goetz et al., 2006). The structure that develops from arf8-4 unfertilized pistil, has been considered for years a parthenocarpic silique because it is longer than wild-type unfertilized pistil and it shows a dehiscence pattern. However, in 2010 Carbonell-Bejerano and collaborators reported that there is a developmental senescence program (that includes the development of the dehiscence zone) which is independent form fertilization and so it is in common between seeded and unfertilized Arabidopsis pistils. In line with this study, our findings suggest that arf8-4 mutant has not a real parthenocarpic phenotype but rather it shows a mis-regulation in the hormones crosstalk, likely due to a truncated protein. This alteration can affect the coordination between growth and senescence of the pistil, modifying the correct progression of the developmental processes. For this reason, at least in Arabidopsis, the only structural characteristic that differentiates arf8-4 parthenocarpic fruit from wild-type unfertilized pistil is the increased size. Further analyses will be necessary to continue investigating arf8-4 phenotype, including high-throughput molecular analyses (mass-spectrometry) about hormones content in the valve tissue and western-blot analysis to confirm definitely the presence of the truncated protein in arf8-4 plants. Overall, the main outcome of this work was that the transcriptome-based gene list on the valve tissue of the Arabidopsis thaliana silique represents a powerful tool for the elucidation of the molecular mechanisms controlling fruit formation. References Carbonell-Bejerano, P., Urbez, C., Carbonell, J., Granell, A. and Perez-Amador, M.A. (2010) A Fertilization-Independent Developmental Program Triggers Partial Fruit Development and Senescence Processes in Pistils of Arabidopsis. Plant Physiol., 154, 163–172. Ferrandiz, C. (2011) Fruit Structure and Diversity. Encycl. Life Sci. Goetz, M., Vivian-Smith, A., Johnson, S.D. and Koltunow, A.M. (2006) AUXIN RESPONSE FACTOR8 Is a Negative Regulator of Fruit Initiation in Arabidopsis. Plant Cell, 18, 1873–1886. Grierson, C.S., Barnes, S.R., Chase, M.W., et al. (2011) One hundred important questions facing plant science research. New Phytol., 192, 6–12. Khush, G.S. (2001) Green revolution: the way forward. Nat. Rev. Genet., 2, 815–822. Whelan, C.J., Wenny, D.G. and Marquis, R.J. (2005) Ecosystems and Human Well-being: Synthesis. Isl. Press. Washington, DC, 1–137.

The lateral line canal system is a sensory organ found in all teleost fish that has a wide range of morphological variation. Variation in morphology may often be the result of evolutionary necessity where the need for function dictates form. Xiphister mucosus is an amphibious Stichaeid fish that inhabits the rocky intertidal zone of the northeastern Pacific Ocean. The rocky intertidal is considered an extreme environment where crashing waves and ebbing tides may require the specialization of adaptations for surviving the many abiotic stressors encountered there. The lateral line trunk canal of Xiphister is regarded as unique among teleosts with multiple, branching, zigzag shaped canals that are morphologically complex. The X. mucosus canal was found to not serve as a mechanosensory organ, rather the findings presented here suggest a new role as a water transport organ. This may be an exaptation to help X. mucosus avoid desiccation during low tides when the fish remain upon the rocky shore and exposed to dehydration. While emersed, Xiphister relies on cutaneous respiration as its primary means of aerial respiration.

ABSTRACT Because of low donation rates in their own country, many Israeli citizens have recently turned to purchasing organs from abroad, risking their lives in highly unsanitary hospital conditions. The trafficking of organs also poses an ethical dilemma for those who sell their organs. Often, these vendors are under-compensated for their body parts, while follow-up medical treatment is minimal. The Jewish faith has always placed the sanctity of human life at its core, and it appears that Judaism allows for the donation of organs, and in some instances, payment for organs. Many Israeli medical professionals have called for a regulated market for organs that is consistent with Jewish ethical values and that compensates the donor for his sacrifice, and ensures that proper medical attention is paid to the recipient. Keywords : Organ-Trafficking, Organ Donation, Jewish Medical Ethics, Regulated Markets, Israel
RÉSUMÉEn raison du faible taux de dons dans leur propre pays, de nombreux citoyens Israéliens ont récemment tourné à l'achat d'organes à partir de l'étranger, au péril de leur vie dans des conditions d'hygiène hospitalière. Le trafic d'organes pose également un dilemme éthique pour ceux qui vendent leurs organes. Souvent, ces fournisseurs sont sous-rémunérés pour leurs parties du corps, tandis que le suivi des traitements médicaux est minime. La religion juive a toujours placé le caractère sacré de la vie humaine, à sa base, et il semble que le judaïsme autorise le don d'organes et, dans certains cas, le paiement pour les organes. Beaucoup de professionnels de la santé israéliens ont appelé à un marché réglementé d'organes qui est compatible avec les valeurs juifs et qui compense le donateur pour son sacrifice, et assure que les soins médicaux est versé au bénéficiaire.Mots-Clés: Trafic D'Organes, Le Don D'Organes, Éthique Médicale Juive, Les Marchés Réglementés, Israël

Mice are the premier model organisms to study human biology and disease, but there is still debate about the extent to which molecular mechanisms are conserved between human and mouse. With the advance of next-generation sequencing technologies, comparative transcriptomics can be carried out at unprecedented resolution. In this thesis we confirm findings that human and mouse transcriptomes are globally conserved and we identify and characterize the properties of a core set of genes with constrained expression between the two species. Additionally, we show that clustering of gene expression across humans, mice and other vertebrates across multiple tissues depends on which genes and samples are included. Finally, we analyze gene expression of primary cells in human to understand how functional units of organs contribute to the expression of an organ as a whole. Indeed, profiling entire organs constitutes one of the main limitations of current comparative studies.
Los ratones son los principales organismos modelos para estudiar la biología y las enfermedades humanas, pero aún está en debate el nivel de conservación molecular entre humanos y ratones. Con el progreso de las tecnologías de secuenciación masiva, la transcriptómica comparativa ha llegado a una resolución sin precedentes. En esta tesis confirmamos que los transcriptomas de humano y ratón están globalmente conservados y identificamos y caracterizamos las propiedades de un conjunto de genes con expresión parecida entre las dos especies. Además, demostramos que diferentes tejidos de humanos, ratones y otros vertebrados se agrupan en base a su expresión génica segón los genes y las muestras incluidas en el análisis. Finalmente, analizamos la expresión génica de líneas celulares primarias humanas para investigar cómo las unidades funcionales de los órganos afectan la expresión de todo un órgano entero. De hecho, los estudios comparativos actuales tienen como limitación que se basan en datos de órganos enteros.

Glucocorticoids are steroid hormones that circulate in the blood to coordinate organismal physiology. They have pleiotropic effects, regulating metabolic, cardiovascular, neural, and immune function. While glucocorticoids are classically thought to be secreted exclusively by the adrenal glands, evidence suggests that different organs may be able to autonomously regulate their local glucocorticoid levels via local production. Local production may be important when circulating glucocorticoids are low or absent, such as in early life of altricial young, which are unable to care for themselves. Immune (lymphoid) organs are particularly interesting candidates for tissue-specific regulation of glucocorticoid levels, as glucocorticoids are necessary for early-life immune development in altricial young. In this dissertation, I present a series of studies using birds and mice to examine whether tissue- specific regulation of glucocorticoids occurs in lymphoid organs. In brief, I report that a) glucocorticoids are locally elevated in lymphoid organs of newly-hatched altricial but not precocial birds, b) glucocorticoids are locally elevated in lymphoid organs of neonatal altricial mice, and c) lymphoid organs of both neonatal and adult mice synthesize glucocorticoids from other steroid precursors. Local glucocorticoid production in lymphoid organs may function to ensure production of functional lymphocytes, and factors that alter lymphoid glucocorticoid levels may play a role in programming the overall immune reactivity.
Science, Faculty of
Zoology, Department of
Graduate

This thesis deals with the structure and innervation of 3 different types of attachments - the fibrous enthesis of the medial collateral ligament, the muscular attachment of the tibialis anterior onto the tibia, and the fibrocartilaginous enthesis organ of the Achilles tendon. Particular attention was paid to the latter and it was shown that in rats at all ages (neonate, 4 week, 4 month, and 2 month) only the retromalleolar fat pad of the enthesis organ was innervated. In the light of these findings, the fat was studied in further detail and an in vitro investigation determined whether nerve fibres are specifically attracted to the adipose tissue. In man, it was confirmed that the equivalent fat pad (Kager's fat pad) was also innervated and a number of anatomical and histopathological observations associated with this tissue in elderly dissecting room cadavers were described.  The relationship between weight, height and foot length with fat pad structure in human cadaveric tissue was investigated, and the effect of the appetite-inducing hormone, ghrelin on the size of the fat pad in the rat was also explored. As entheses are the primary target organs in the seronegative spondyloarthropathies (autoinflammatory rheumatic conditions), the presence of resident and inflammatory macrophages and neutrophils in the rat Achilles tendon enthesis organ was investigated at a variety of ages. Overall, it was concluded that adipose tissue associated with entheses may play a role in proprioception and be a source of pain in enthesopathies.

The aim of the project was to develop a new Artificial Intelligence-based method to aid modeling of musical instruments and sound design. Despite significant advances in music technology, sound design and synthesis of complex musical instruments is still time consuming, error prone and requires expert understanding of the instrument attributes and significant expertise to produce high quality synthesised sounds to meet the needs of musicians and musical instrument builders. Artificial Intelligence (Al) offers an effective means of capturing this expertise and for handling the imprecision and uncertainty inherent in audio knowledge and data. This thesis presents new techniques to capture and exploit audio expertise, following extended knowledge elicitation with two renowned music technologist/audio experts, developed and embodied into an intelligent audio system. The Al combined with perceptual auditory modeling ba.sed techniques (ITU-R BS 1387) make a generic modeling framework providing a robust methodology for sound synthesis parameters optimisation with objective prediction of sound synthesis quality. The evaluation, carried out using typical pipe organ sounds, has shown that the intelligent audio system can automatically design sounds judged by the experts to be of very good quality, while significantly reducing the expert's work-load by up to a factor of three and need for extensive subjective tests. This research work, the first initiative to capture explicitly knowledge from audio experts for sound design, represents an important contribution for future design of electronic musical instruments based on perceptual sound quality will help to develop a new sound quality index for benchmarking sound synthesis techniques and serve as a research framework for modeling of a wide range of musical instruments.

Thesis: S.M., Massachusetts Institute of Technology, Department of Mechanical Engineering, 2018.
This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.
Cataloged from student-submitted PDF version of thesis.
Includes bibliographical references (pages 255-260).
MicroPhysiological Systems (MPS), also called organs-on-chips, attempt to mimic the relevant human multi-organ physiology in-vitro. They have potential applications in drug development and personalized medicine by enabling more accurate testing of physiological drug response earlier in the development cycle. On-platform pumps provide greater flexibility and design freedom and are a key feature of such platforms. One approach to multi-organ MPS platforms has been developed in our lab and uses an open-well system to culture tissues of various organs. A common fluid-media circulates between the organs using on-platform pneumatic diaphragm micro-pumps. These pumps require significant effort in setup and depend on external pressure and vacuum sources. An independent, portable pump with low power consumption is desirable. There are also on-going efforts in the field to make sterile platform components low-cost and single use, to reduce user setup time and sterilization effort. This thesis describes a scaled-up version of an ElectroMagnetic (EM) pump. The pump uses a teeter-totter EM actuator having a low energy consumption of about 1 mJ/stroke. The EM actuator minimizes energy by a latching design that requires a short pulse of energy only to switch its state and its springs store energy which is recovered in the reverse stroke. This thesis also describes injection-molded, single-use platforms with onboard pneumatic diaphragm micro-pumps. It describes various valve and pump geometries and a model to predict large deflections of polymer diaphragms. We integrate the EM actuators with these platforms, demonstrating temperature rise of less than 0.1 'C, valve sealing up to 60 kPa, and a pumping frequency of 1 Hz, limited by diaphragm behavior. In addition, we improve platform features using spillways which allow for better passive leveling of fluid height between MPSes. This thesis also presents the selection of polymer tubing to resolve condensation issues in pneumatic channels of an MPS platform inside a cell culture incubator.
by Brij M. Bhushan.
S.M.

Orientador: Izabelle Auxiliadora Molina de Almeida Teixeira
Coorientador: Carla Joice Härter
Banca: Rafael Fernandes Leite
Banca: Kleber Tomas de Resende
Resumo: Este trabalho foi realizado utilizando informações de 7 estudos, em que foram ajustadas curvas de crescimento ao desenvolvimento dos órgãos do sistema visceral de fêmeas, machos castrados e machos inteiros da raça Saanen de 0,5 a 19,5 meses de idade. Inicialmente, foram avaliados oito modelos: Regressão linear simples; Quadrático; Monomolecular; Brody; Von Bertalanffy; Logística; Gompertz; e Richards. Os dados dos órgãos viscerais (fígado, pâncreas, baço, rúmen-retículo, omaso, abomaso, intestino delgado e intestino grosso) e tecido adiposo mesentérico (TAM), foram ajustados nos modelos usando o procedimento NLMIXED do SAS. O melhor modelo ajustado foi escolhido com base no Critério de Informações Akaike corrigido para pequenas amostras (AICc) e nos coeficientes de correlação de concordância (CCC). Após a escolha do modelo que melhor ajustou a curva de crescimento dos órgãos viscerais avaliados, modelamos a variância buscando um melhor ajuste. Os parâmetros dos modelos para cada sexo foram comparados utilizando o comando CONTRAST (p < 0,10). Em geral, o modelo que melhor descreveu o crescimento de órgãos do sistema visceral foi o logístico (menor AICc e maior CCC). Quando os órgãos foram expressos em gramas, o sexo não influenciou os parâmetros das equações para predição do crescimento dos órgãos avaliados (p > 0,10), exceto o MAT (p < 0,02); em que as fêmeas apresentaram menor taxa de deposição comparada aos machos inteiros e castrados (0,318 ± 0,034 vs 0,659 ± 0,062), e um ... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: This work was performed gathering information of 7 studies, in which growth curves were fitted to the visceral organs of female, intact male, and castrated male Saanen goats from 0.5 to 19.5 months old. Initially, eight models were assessed: Monomolecular; Simple linear regression; Quadratic; Monomolecular; Brody; Von Bertalanffy; Logistics; Gompertz; and Richards. Data of the visceral organs (liver, pancreas, spleen, rumen-reticulum, omasum, abomasum, small intestine, and large intestine) and mesenteric adipose tissue (MAT) were fitted in the models using NLMIXED procedure of SAS. The best fitted model was choosing based on the Akaike Corrected Information Criterion for small samples (AICc) and values and the concordance correlation coefficient (CCC). After choosing the model that best fitted the growth curve of the evaluated visceral organs, we modelled the variance seeking a better fit. Parameters of the models for each sex were compared using the CONTRAST statement (p < 0.10). Overall, the model that best described visceral organ growth was the logistic (i.e., lower AICc and higher CCC). When organs were expressed in grams, the sex did not influence the parameters of equations to predict the growth of the evaluated organs (p > 0.10), except for TAM (p < 0.02); females presented a lower deposition rate compared to intact males and castrated males (0.318 ± 0.034 vs 0.659 ± 0.062), and a inflection point higher than intact males and castrated males (7.65 vs 3.69 months). However, this difference between the sexes is not found when TAM is expressed in % to empty body weight (EBW). Irrespective of sex, at the beginning of growth, liver stood for 2.75 ± 0.113 % of EBW, grew (g) at a maximum rate of 0.531 ± 0.062, and its inflection point of the curve occurred at 1.7 months. The gastrointestinal t... (Complete abstract click electronic access below)
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Este trabalho foi realizado utilizando informações de 7 estudos, em que foram ajustadas curvas de crescimento ao desenvolvimento dos órgãos do sistema visceral de fêmeas, machos castrados e machos inteiros da raça Saanen de 0,5 a 19,5 meses de idade. Inicialmente, foram avaliados oito modelos: Regressão linear simples; Quadrático; Monomolecular; Brody; Von Bertalanffy; Logística; Gompertz; e Richards. Os dados dos órgãos viscerais (fígado, pâncreas, baço, rúmen-retículo, omaso, abomaso, intestino delgado e intestino grosso) e tecido adiposo mesentérico (TAM), foram ajustados nos modelos usando o procedimento NLMIXED do SAS. O melhor modelo ajustado foi escolhido com base no Critério de Informações Akaike corrigido para pequenas amostras (AICc) e nos coeficientes de correlação de concordância (CCC). Após a escolha do modelo que melhor ajustou a curva de crescimento dos órgãos viscerais avaliados, modelamos a variância buscando um melhor ajuste. Os parâmetros dos modelos para cada sexo foram comparados utilizando o comando CONTRAST (p < 0,10). Em geral, o modelo que melhor descreveu o crescimento de órgãos do sistema visceral foi o logístico (menor AICc e maior CCC). Quando os órgãos foram expressos em gramas, o sexo não influenciou os parâmetros das equações para predição do crescimento dos órgãos avaliados (p > 0,10), exceto o MAT (p < 0,02); em que as fêmeas apresentaram menor taxa de deposição comparada aos machos inteiros e castrados (0,318 ± 0,034 vs 0,659 ± 0,062), e um ponto de inflexão superior ao dos machos inteiros e castrados (7,7 vs 3,7 meses). No entanto, essa diferença entre os sexos não é encontrada quando o MAT é expresso em % ao peso do corpo vazio (PCV). Independentemente do sexo, no início do crescimento, o fígado representou 2,75 ± 0,113 % do PCV, cresceu (g) a uma taxa máxima de 0,531 ± 0,062, e o ponto de inflexão de sua curva ocorreu em 1,7 meses. O trato gastrointestinal (TGI) representou 9,14 ± 0,493 % PCV, e à medida que os animais cresceram o TGI diminuiu sua porcentagem em relação ao PCV a uma taxa constante de 0,135 ± 0,046 %. Considerando o período avaliado, em geral, o rúmen-retículo e o intestino grosso aumentaram sua porcentagem em relação ao PCV e TGI, enquanto o abomaso e o intestino delgado diminuíram sua porcentagem em relação ao PCV e TGI, à medida que o animal crescia. O rúmen-retículo e o intestino grosso, que estão diretamente relacionados à digestão de alimentos sólidos, apresentaram maiores taxas de crescimento nos dois primeiros meses de vida. Os resultados evidenciaram que o sexo não afeta o crescimento de órgãos do sistema visceral (g), exceto para MAT, porém, quando olhamos em % PCV alguns órgãos mostram diferenças entre os sexos, como o fígado, abomaso, intestino delgado, intestino grosso e intestinos. O conhecimento da curva de crescimento dos órgãos viscerais pode ser muito útil para melhorar a compreensão de seu impacto sobre as exigências nutricionais desses animais, e ser utilizado para otimizar ou desenvolver um plano nutricional adequado para cada fase de crescimento, como também auxiliar os produtores a desenvolver planos estratégicos em um rebanho de caprinos, como a melhor idade para desmame e abate desses animais.
This work was performed gathering information of 7 studies, in which growth curves were fitted to the visceral organs of female, intact male, and castrated male Saanen goats from 0.5 to 19.5 months old. Initially, eight models were assessed: Monomolecular; Simple linear regression; Quadratic; Monomolecular; Brody; Von Bertalanffy; Logistics; Gompertz; and Richards. Data of the visceral organs (liver, pancreas, spleen, rumen-reticulum, omasum, abomasum, small intestine, and large intestine) and mesenteric adipose tissue (MAT) were fitted in the models using NLMIXED procedure of SAS. The best fitted model was choosing based on the Akaike Corrected Information Criterion for small samples (AICc) and values and the concordance correlation coefficient (CCC). After choosing the model that best fitted the growth curve of the evaluated visceral organs, we modelled the variance seeking a better fit. Parameters of the models for each sex were compared using the CONTRAST statement (p < 0.10). Overall, the model that best described visceral organ growth was the logistic (i.e., lower AICc and higher CCC). When organs were expressed in grams, the sex did not influence the parameters of equations to predict the growth of the evaluated organs (p > 0.10), except for TAM (p < 0.02); females presented a lower deposition rate compared to intact males and castrated males (0.318 ± 0.034 vs 0.659 ± 0.062), and a inflection point higher than intact males and castrated males (7.65 vs 3.69 months). However, this difference between the sexes is not found when TAM is expressed in % to empty body weight (EBW). Irrespective of sex, at the beginning of growth, liver stood for 2.75 ± 0.113 % of EBW, grew (g) at a maximum rate of 0.531 ± 0.062, and its inflection point of the curve occurred at 1.7 months. The gastrointestinal tract (GIT) stood for 9.14 ± 0.493 % EBW, and as the goats grew the GIT decreased its percentage in relation to the EBW at a constant rate of 0.135 ± 0.046 %. Considering the evaluated period, in general rumen-reticulum and large intestine increased their percentage in relation to EBW and GIT, whereas abomasum and small intestine decreased their percentage in relation to EBW and GIT, as animal grew. The rumen-reticulum and large intestine, which are directly related to the digestion of solid foods, presented higher growth rates in the first two months of life. The results highlighted that sex does not affect the growth of visceral organs (g), except for TAM. However, when we look at % EBW, some organs show differences between the sexes, such as the liver, abomasum, small intestine, large intestine and Intestines. Knowledge of the growth curve of the visceral organs can be very useful in improving the understanding of their impact on the nutritional requirements of these animals and can be used to optimize or develop a nutritional plan suitable for each growth phase, but also to help producers develop strategic plans for a herd of goats, such as the best age for weaning and slaughtering these animals.

L'auxine est impliquée dans la mise en place de la phyllotaxie chez les angiospermes. Chez l'arabette, cette hormone est transportée de façon polarisée dans la racine et dans la tige. Elle est accumulée dans les groupes de cellules qui évolueront en primordia latéraux. Son transport est organisé par des transporteurs putatifs à efflux de l'auxine. L'un d'eux, PIN1, est exprimé au niveau du méristème apical caulinaire (MAC). Son patron d'expression nous a permis de créer un modèle pour le fonctionnement de la phyllotaxie chez l'arabette. Ce modèle inclut les données d'expression de gènes marqueurs des primordia (LFY, ANT), de l'identité meristématique (STM) et des bordures entre le MAC et les primordia (CUC1), en réponse aux flux d'auxine créés par la polarisation de PIN1. Dans le maïs nous avons cloné deux orthologues de PIN1: ZmPIN1a et ZmPIN1b. Leur expression a été etudiée par hybridation in situ et immunolocalisation. La protéine est localisée de façon polarisée dans les tissus végétatifs et dans les structures reproductives. Cette polarisation change selon le stade de développement et les organes considerés. Dans les inflorescences mâle et femelle les flux d'auxine pourraient déterminer la mise en place des ramifications de différents ordres ainsi que l'identité des méristèmes. L'ensemble de ces données montre donc que l'expression de PIN1 dans les inflorescences est différente chez le maïs et chez l'arabette
Auxin is involved in phyllotaxy establishment in angiosperms. In Arabidopsis, this hormone is polarly transported in the root and n the shoot. It is accumulated into groups of cells that will form lateral primordia. Its transport is set by putative auxin efflux carriers. One of these, PIN1, is expressed in the Shoot Apical Meristem (SAM). Its expression pattern allowed to create a model for phyllotaxy establishment in Arabidopsis. This model includes the expression data of primordia marker genes (LFY, ANT), meristematic identity (STM) and genes expressed at the borders between the SAM and the primordia (CUC1), in response to auxin fluxes created by the PIN1 polarization. We have identified two orthologous genes for PIN1 in maize : ZmPIN1a and ZmPIN1b. Their expression has been studied by in situ hydridization and immunolocalization. The protein is localized in a polar pattern in both vegetative and reproductive structures. This polar pattern changes according to the developmental stage and organs considered. In male and female inflorescences the auxin fluxes could determine the formation of the different orders of branching and also the meristematic identity of cells. Globally these data suggest that the expression of PIN1 in inflorescences is different in maize than in Arabidopsis

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Conselho Nacional de Desenvolvimento Científico e Tecnológico
Este estudo foi dividido em 3 experimentos objetivando-se: 1) investigar os efeitos da supernutrição materna sobre o desenvolvimento gonadal e expressão gênica hipofisário- gonadal em fetos bovinos no terço final da gestação. Vinte e sete vacas secas multíparas foram alimentados ad libitum (E) ou em nível de mantença (M) de mesma dieta. Doze vacas de H (n = 6) e M (n = 6) gestantes de fetos do sexo feminino foram submetidos à eutanásia aos 199 e 268 dias de gestação (DG; n = 3 para H ou M em cada DG). Quinze vacas de H (n = 6) e M (n = 9) gestantes de fetos masculinos foram sacrificados aos 139, 199 e 241 DG (n = 2 para H e n = 3 para M em cada DG). 2) Avaliar os efeitos de diferentes planos nutricionais no desenvolvimento do parênquima mamário (PAR), na expressão de marcadores lipogênicos (CD36, ACCA, FASN, ADIPOR1), nas concentrações de hormônios no sangue e expressão hepática dos genes GHR, IGF1, IGFBP2 e IGFBP3 em novilhas pre-púberes. Dezoito novilhas foram alimentadas 1 de 3 planos nutricionais (n = 6 / tratamento) para sustentar um ganho médio diário (GMD), como segue: alto ganho (AG-1 kg/d), baixo ganho (BG- 0,5 kg/d) ou mantença (MA). 3) Elucidar se os padrões de expressão dos genes ESR1, GDF9, FSHR, LHR, BMPR2, TGFB1, TGFB2, BMP15, BMP6, BMP7, CYP19A1, HSD3B1, IGFR, IGF1 e IGF2 poderiam estar envolvido na modulação do início da puberdade em novilhas da raça Brahman. No primeiro experimento, os números de folículos primordiais e totais foram menores nos ovários dos fetos oriundos de vacas alimentadas E do que das vacas M. Estes resultados foram opostos para folículos pré-antrais e antrais. As proporções volumétricas e os diâmetros dos cordões seminíferos foram menores nos testículos dos fetos oriundos das vacas alimentadas E em comparação as vacas M. A expressão pituitária do gene FSH foi maior nos fetos fêmeas de vacas alimentadas E do que das vacas M, independentemente do DG, ao passo que a expressão do gene LHB não diferiu. As expressão ovarianas fetais dos genes P450 aromatase, StAR, BMPR2, TGFB1, GDF9, FSHR, Bax e CASP3 foram maiores dos fetos oriundos das vacas alimentadas E do que 5 das vacas M, independentemente do DG. As expressões testiculares fetais dos genes StAR, HSD17B3, IGF1, IGF2 e IGF1R foram maiores dos fetos oriundos das vacas alimentadas M do que das vacas E. De modo geral, a ingestão materna ad libitum parece afetar o crescimento folicular ovariano fetal e números de folículos, o qual pode influenciar o tamanho da reserva ovariana em sua prole. Nos fetos machos, a ingestão materna ad libitum parece perturbar o desenvolvimento testicular e pode ter implicações na produção de esperma. No segundo experimento, os pesos dos PAR mamário e relação PAR/GM foram menores nas novilhas de AG do que novilhas de MA e BG, visto que a gordura extraparenquimal mamária foi maior nas novilhas de AG do que em outros grupos. Novilhas alimentadas para AG apresentaram maior fração de lipídica e menor fração proteica no PAR. No entanto, o número de adipócitos intraparenquimais foi semelhante entre os grupos. Novilhas alimentadas para AG tiveram maior concentração sérica de IGF1 do que outros, e a concentração sérica de insulina foi menor nas novilhas de AG em comparação as novilhas de MA e BG. Os genes GHR, IGF1 e IGFBP3 foram up-regulados enquanto o gene IGFBP2 foi down-regulado no fígado das novilhas de HG relação aos outros grupos. Os genes CD36, ACCA, FASN e ADIPOR1 foram-se up- regulados pelo nível de ingestão de nutrientes. No geral, estes resultados demonstram que a elevada ingestão de nutrientes favoreceu ao acúmulo de gordura corporal e na glândula mamária. Estes resultados poderiam servir como preditores do comprometimento do desenvolvimento mamário. Finalmente, os dados qRT-PCR obtidos no terceiro experimento revelaram maior expressão dos genes FSHR, BMP7, CYP19A1, IGF1 e IGF1R em novilhas pre-púberes em comparação as novilhas pós- púberes. Além disso, a expressão do gene IGF1 foi positivamente correlacionada com a expressão do gene BMP7 (P = 0.07; r = 0.84) e a expressão do HSD3B1 foi negativamente correlacionada com a expressão do gene CY19A1 (P = 0.3; r = -0.90). Estes resultados sugerem que a expressão diferencial dos genes ovarianos pode estar associado com as alterações na dinâmica folicular e diferentes tipos de populações celulares, os quais surgiram como consequência da puberdade e a fase lútea. A hipótese que emerge é que dois reguladores-chave da atividade do ovário pré-puberdade, BMP7 e IGF1 modulam a expressão de FSHR, LHR, IGFR1 e CYP19A1. BMP7 parece regular LHR e up-regular FSHR e CYP19A1, que medeiam a dinâmica folicular ovariana dessas 6 novilhas. Portanto, BMP7 e IGF1 parecem desempenhar papéis reguladores sinérgicos e foram previstos interagir entre si.
This study was divided in three experiments that aimed to: 1) investigate effects of maternal overnutrition on gonadal development and pituitary-gonadal gene expression in cattle fetuses at mid and late gestation. Twenty-seven multiparous dry cows were fed either high (ad libitum, H) or moderate (M) intake of the same diet. Twelve cows from H (n=6) and M (n=6) intake carrying females fetuses were euthanized at 199 and 268 days of gestation (DG; n=3 for H or M on each DG). Fifteen cows from H (n=6) and M intake (n=9) carrying male fetuses were euthanized at 139, 199 and 241 DG (n=2 for H and n=3 for M on each DG). 2) To evaluate effects of different planes of nutrition on mammary parenchyma (PAR) development, expression of lipogenic marks (CD36, ACCA, FASN, ADIPOR1), concentrations of blood hormones and liver GHR, IGF1, IGFPB-2 and -3 mRNA expression in prepubertal heifers. Eighteen heifers were fed 1 of 3 nutrient intake levels (n = 6/treatment) designed to sustain an average daily gain (ADG), as follows: high gain (HG-1 kg/d), low gain (LG- 0.5 kg/d) or maintenance (MA). 3) To elucidated if the expression pattern of ESR1, GDF9, FSHR, LHR, BMPR2, TGFB1, TGFB2, BMP15, BMP6, BMP7, CYP19A1, HSD3B1, IGF1, IGFR1 and IGF2 genes could be involved in modulate the timing of puberty in Brahman heifers. In the first experiment, primordial and total follicle numbers were lower in fetal ovaries from H than in M intake cows. These results were reverse for preantral and antral follicles. Volumetric proportion and diameter of seminiferous cord were lower in fetal testis of H than M intake cows. The expression level of FSHB was greater in pituitary gland of female fetus from H compared to M intake cows, irrespective of DG, whereas LHB gene expression did not differ. In males, FSHB and LHB gene expression levels were similar between maternal intake groups. Fetal ovarian expression of P450 aromatase, StAR, BMPR2, TGFBR1, GDF9, FSHR, Bax and CASP3 genes were higher in H than in M intake cows, irrespective of DG. Fetal testicular expression of StAR, HSD17B3, IGF1, IGF2 and IGF1R genes were higher in M than in H intake cows. Overall, maternal H intake seems to affect fetal ovarian follicular growth and number of follicles, which may 8 affect size of ovarian reserve in their offspring. In male fetus, maternal H intake seems to disturb testicular development and may have implications on sperm production. In the second experiment, mammary PAR weight and MA to MG ratio was lower in HG than MA and LG heifers, whereas mammary extraparenchymal fat was greater in HG heifers than other groups. Heifers fed the HG had a greatest fraction of lipids in their PAR, and smallest fraction of protein in their PAR. However, the number of intraparenchymal adipocytes was similar between the groups. Heifers fed the HG had greater serum IGF1 than others, and serum insulin was lower in MA than HG and LG heifers. The liver GHR, IGF1 and IGFBP3 mRNA was higher whereas IGFBP2 mRNA was lower in HG heifers compared to others. The expression of CD36, ACCA, FASN and ADIPOR1 were up regulated by nutrient intake level. Overall, these results demonstrated that enhancing nutrient intake favored to fat accumulation on body and mammary gland, also resulted adipocyte hypertrophy in the PAR of HG heifers, which could be a predictor of impaired mammary development. Finally, qRT-PCR data from the third experiment revealed the expression of FSHR, BMP7, CYP19A1, IGF1 and IGFR1 mRNA was greater in PRE heifers, when contrasted to POST heifers. In addition, the expression of IGF1 mRNA was positively correlated with BMP7 mRNA (P = 0.07, r = 0.84) and the expression of HSD3B1 mRNA was negatively correlated with expression of CY19A1 mRNA (P = 0.03, r = -0.90). Taken together, these results suggest that the differential expression of ovarian genes could be associated with changes in follicular dynamics and different cell populations that have emerged as consequence of puberty and the luteal phase. The emerging hypothesis is that two key regulators of ovarian activity pre-puberty, BMP7 and IGF1 modulate the expression of FSHR, LHR, IGFR1 and CYP19A1. BMP7 seems to down-regulate LHR and up-regulate FSHR and CYP19A1, which mediates the follicular dynamics in heifer ovaries. Thus, BMP7 and IGF1 seem to play synergic regulatory roles and were predicted to interact.

This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.
Thesis: Ph. D., Massachusetts Institute of Technology, Department of Biology, 2019
Cataloged from student-submitted PDF version of thesis.
Includes bibliographical references.
Metastasis is the cause of the vast majority of cancer-related deaths, yet much remains unknown about this complex process, from how tumor cells complete the many steps of the metastatic cascade to how they can adapt to survive in multiple, vastly different secondary sites. I have therefore conducted two studies into different aspects of metastasis. First, I investigated the scaffold protein IQGAP1, which promotes primary tumor growth and invasiveness in several cancers. However, the role of IQGAP1 in metastasis has been unclear. We used IQGAP1 knockdown and knockout to investigate its role in the metastatic cascade in melanoma and breast cancer. I found that reduction of IQGAP1 expression inhibited the formation of metastases, without limiting primary or metastatic tumor growth. Furthermore, IQGAP1 knockout significantly decreased extravasation of tumor cells from circulation.
These data demonstrate that IQGAP1 promotes metastasis in vivo through regulation of extravasation and suggest that it may represent a valid therapeutic target for inhibiting metastasis. Second, I examined how cells from the same primary tumor can adapt to several different secondary environments. A critical component of every metastatic niche is the extracellular matrix (ECM), which provides structural support, migration control, and growth and survival signals. However, a comprehensive comparison of the ECM components of metastatic niches at various secondary sites had not yet been conducted. I isolated metastases from the brain, lungs, liver and bone marrow, which were all derived from parental MDA-MB-231 human breast cancer cells. We then enriched these tumor samples for ECM proteins and used quantitative mass spectrometry to analyze their ECM composition. Strikingly, the niches created at each site were distinct.
Using these data, I compared protein abundance across all metastatic sites to determine which ECM proteins were most significantly elevated in each particular tissue relative to the others. Following this analysis, I knocked down tumor cell expression of SERPINB1, a protein characteristically elevated in brain metastases, and observed reduced metastasis to the brain. Together, these studies offer insight into the fundamental biology of metastasis and metastatic niches, as well as provide potential targets of metastatic breast cancer for imaging and therapy.
by Jess Dale Hebert.
Ph. D.
Ph.D. Massachusetts Institute of Technology, Department of Biology