Indiana University-Purdue University Indianapolis (IUPUI) / Pancreatic ductal adenocarcinoma (PDA) is a deadly disease due to early metastasis and resistance to chemotherapy. PDA is commonly associated with a dense desmoplastic stroma, which forms a protective niche for cancer cells. Tissue transglutaminase (TG2), a Ca2+-dependent enzyme, is abundantly expressed in pancreatic cancer cells and crosslinks proteins through acyl-transfer transamidation between glutamine and lysine residues. The objective of the study was to determine the functions of TG2 in the pancreatic stroma. Orthotopic pancreatic xenografts and co-culture systems tested the mechanisms by which the enzyme modulates tumor-stroma interactions. We showed that TG2 secreted by cancer cells is enzymatically active and renders the stroma denser by crosslinking collagen, which in turn activates fibroblasts and stimulates their proliferation. Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) are transcription factors involved in mechanotransduction. The TG2-mediated fibrosis-rich, stiff microenvironment conveys mechanical cues to cancer cells leading to activation of YAP and TAZ, promoting cell proliferation and tumor growth. Stable knockdown of TG2 in pancreatic cancer cells led to decreased size of pancreatic xenografts and increased sensitivity of xenografts to gemcitabine. Taken together, our results demonstrate that TG2 secreted in the tumor microenvironment orchestrates the crosstalk between cancer cells and the stroma, fundamentally impacting tumor growth and response to chemotherapy. Our study supports TG2 inhibition in the pancreatic stroma as a novel strategy to block pancreatic cancer progression.

As an indirect consequence of increased heat cooling requirements, personal computers (PC) have become noisier due to the increased use of fans. Hard disk drives also contribute to the annoying noise radiated by personal computers, creating a need for the control of computer noise. Due to size constraints, the implementation of passive noise control techniques in PC is difficult. Alternatively, active noise control (ANC) may provide a compact solution to the noise problems discussed above, which is the subject of this work. First, the computer noise sources were characterized. The structure-borne path was altered passively through the decoupling of the vibrating sources from the chassis. Global noise control strategy was then investigated with a hybrid passive/active noise control technique based on folded lined ducts, integrating microphones and speakers, that were added to the PC air inlet and outlet. While the ducts were effective above 1000Hz, the use of a MIMO adaptive feedforward digital controller lead to significant noise reduction at the ducts outlets below 1000Hz. However, global performance was limited due to important airborne flanking paths. Finally, the same type of controller was used to create a zone of quiet around the PC user head location. It was implemented using multimedia speakers and microphones, while the computer was placed in a semi-reverberant environment. A large zone of quiet surrounding the head was created at low frequencies (250Hz), and its size would reduce with increasing frequency (up to 1000Hz). / Master of Science

Mayer-Rokitansky-Kuster-Hauser Syndrome is a congenital disorder of the female reproductive tract due to impaired Müllerian duct development. There are three known categorical presentations: isolated, atypical, and MURCS association. Several developmentally significant factors including inappropriate AMH/AMHR interaction, and mutations in the WNT gene family and HOXA7-13 cluster have been studied. There has also been investigation into an autosomal dominant pattern of inheritance in families with multiple cases of the syndrome. Due to the presence of multiple subsets of patients with similar genetic abnormalities, it seems unlikely that a single etiology will be discovered.

Thesis (MScMedSc)--Stellenbosch University, 2015. / ENGLISH ABSTRACT: Diabetes Mellitus is a metabolic disease characterized by the loss of beta cells from the islets, thereby disrupting islet composition and architecture which are important components that influence islet function. The experimental technique of pancreatic duct ligation (PDL), which is thought to induce the regeneration of beta cells within the adult pancreas, was investigated as a novel treatment strategy for diabetes. This study aimed at investigating the possibility that the PDL model may have the capacity to restore normal islet composition and architecture in diabetic animals, which could make it an effective approach to reverse diabetes. Male Wistar rats (n=55) were divided into three study groups: the normal control (NC) group, the diabetic control (DC) group consisting of five subgroups (day 0, 3, 5, 10 and 30) and the experimental (EX) group consisting of four subgroups (day 3, 5, 10 and 30). The experimental group was exposed to PDL. All pancreata were divided into a P1 portion (proximal to the point of ligature) and P2 portion (distal to the point of ligature) for histological assessment. Animals’ non-fasting blood glucose levels (BGLs) and body weights were monitored. The general morphology of the tissue was studied, while an immunohistochemical (IHC) study was performed to determine insulin, pancreatic polypeptide, glucagon and somatostatin protein expression in the P1 and P2 portions of the pancreas. From the IHC slides hormone fractions, staining intensity and distribution were determined as indication of islet composition and architecture. Despite apparent morphological recovery in the islet 30 days post-PDL, islet composition and architecture remained disrupted. Compared to diabetic animals, the proximal portion of the pancreas in experimental animals had a decreased beta cell fraction and increased delta cell fraction thirty days following PDL. These observed changes in islet composition in the part of the pancreas proximal to the ligature are novel findings. There was no change in the diabetic islet composition in the portion of the pancreas distal to the ligature thirty days following PDL. Furthermore, pancreatic duct ligation did not restore body weight or normoglycemia. We conclude that STZ disrupts islet composition and architecture and this could not be restored using PDL; we therefore suggest that a comparative study using a Type 2 diabetic model, where there is limited damage to pre-existing beta cells, may yield different results. / AFRIKAANSE OPSOMMING: Diabetes Mellitus is ʼn metaboliese siekte wat deur die verlies van beta selle uit die eilande van Langerhans gekarakteriseer word. Hierdie verlies van beta selle ontwrig eiland komposisie en argitektuur, twee belangrike komponente van eiland funksie. Die eksperimentele tegnieke van pankreatiese buisafbinding (in Engels PDL), wat moontlik beta sel regenerasie in die volwasse pankreas kan induseer, is ondersoek as behandelings-strategie vir diabetes. Hierdie studie het ten doel gehad om die moontlikheid te ondersoek dat die PDL model die kapasiteit het om normale eiland komposisie en argitektuur te herstel in diabetiese diere, wat dit ʼn effektiewe benadering vir die omkeer van diabetes kan maak. Manlike Wistar rotte (n=55) was in 3 studie groepe verdeel: die normale kontrole (NC) groep, die diabetiese kontrole (DC) groep wat uit vyf subgroepe bestaan (dag 0, 3, 5, 10 en 30) en die eksperimentele (EX) groep wat uit vier subgroepe bestaan (dag 3, 5, 10 en 30). Die eksperimentele groep is aan PDL blootgestel. Alle pankreata is verdeel in ʼn P1 porsie (proksimaal tot die afbinding) en ʼn P2 porsie (distaal tot die afbinding) vir histologiese assessering. Die diere se nie-vastende bloed glukose vlakke en liggaamsgewig is gemonitor. Die algemene morfologie van die pankreas weefsel is bestudeer, terwyl ’n immunohistochemiese (IHC) studie gedoen is om insulien, pankreatiese polipeptied, glukagon en somatostatien proteïen uitdrukking in die P1 en P2 porsies van die pankreas te bepaal. Vanaf die IHC snitte is hormoon fraksie, kleur intensiteit en verspreiding bepaal as aanduidings van eiland komposisie en argitektuur. Ten spyte van ooglopende morfologiese herstel in die eilande op dag 30 na PDL, het eiland komposisie en argitektuur versteur gebly. In vergelyking met die diabetiese diere, het die proksimale deel van die pankreas van eksperimentele diere verlaagde beta sel fraksie en verhoogde delta sel fraksie getoon dertig dae na PDL. Die waarneming van veranderde komposisie in die deel van die pankreas proksimaal tot die afbinding is nuut. Daar was geen verandering in diabetiese eiland komposisie in die deel van die pankreas distaal tot die afbinding dertig dae na PDL nie. Verder het PDL nie liggaamsgewig of bloedsuiker genormaliseer nie. Ons gevolgtrekking is dat STZ eiland komposisie en argitektuur ontwrig en dat dit nie met PDL herstel kon word nie; daarom stel ons ʼn vergelykende studie in ʼn tipe 2 diabetes model voor, waar die skade aan reeds bestaande beta selle beperk is, wat ander resultate mag lewer.

Les récepteurs couplés aux protéines G (RCPG) sont impliqués dans la majeure partie des communications intercellulaires. Un grand nombre de RCPG ont été découverts en comparant la séquence des récepteurs connus avec les données fournies par le séquençage du génome humain. Pour plus d'une centaine de ces récepteurs, le ligand activateur ou agoniste est inconnu. Ces récepteurs sont dès lors qualifiés d'orphelins. Les LGR forment une sous-famille de RCPG structurellement proches de la rhodopsine qui comprend les récepteurs aux hormones glycoprotéiques (TSH, LH, hCG, FSH) et à la relaxine. LGR4 est un membre de cette famille dont ni la fonction précise, ni l'agoniste ne sont connus. Dans un premier temps, une cartographie détaillée de l'expression de Lgr4 chez la souris a été obtenue. Nous avons tiré parti de l'existence d'une lignée de souris transgéniques dont le gène Lgr4 a été interrompu par l'introduction d'une cassette comportant deux marqueurs histologiques. L'activité beta-galactosidase d'un de ces marqueurs a été analysée chez les souris hétérozygotes. Ces dernières ne présentent pas de phénotype particulier, ce qui permet d'estimer que l'expression des marqueurs rend effectivement compte de l'expression normale du gène Lgr4. Lgr4 est exprimé dans un grand nombre de structures, notamment dans le cartilage, le rein, les appareils reproducteurs mâle et femelle et certaines cellules du système nerveux. Ensuite, le phénotype des souris homozygotes pour l'inactivation de Lgr4 (LGR4KO) a été exploré. Ces souris présentent à la naissance un poids inférieur à leurs congénères des autres phénotypes. Les mâles sont stériles à cause d'une malformation des tubules efférents et de l'épididyme. Un blocage au niveau des tubules efférents reliant le testicule à l'épididyme contraint les spermatozoïdes à s'accumuler à la sortie du testicule, dans la région du rete testis. De plus, les tubes de l'épididyme, pourtant normaux à la naissance, ne s'allongent pas pour former la structure convolutée habituelle. L'épithélium de ces tubes est aplati et est entouré d'une quantité anormalement élevée de mésenchyme. Dans un troisième temps, des outils nécessaires aux futures tentatives d'identification de l'agoniste naturel de LGR4 ont été réalisés. Il s'agit : (1) d'anticorps monoclonaux dirigés contre la partie extracellulaire du récepteur humain. (2) d'un appât moléculaire pour la ‘pêche au ligand’. Cet appât est constitué du domaine extracellulaire du récepteur humain couplé à un marqueur histologique. (3) d'une construction peptidique constituée du domaine extracellulaire du récepteur humain couplé à une queue poly-histidine. Cette construction est destinée à servir de greffon lors de chromatographies d'affinités devant permettre de purifier le ligand. (4) de lignées cellulaires exprimant le récepteur LGR4 humain ainsi que le système æquorine devant permettre de détecter l'activation de ce récepteur. Les données apportées par ce travail montrent un rôle important du récepteur LGR4 au cours du développement et permettent de circonscrire le champ des recherches futures. Ceci, ainsi que les outils moléculaires développés, constitue une base pour l'identification future de l'agoniste et la détermination précise de la fonction de LGR4.

<p>Fans are often used in equipment such as home appliances andelectronic equipment where the margin of profit is small butcustomers demands on a low noise level are high. Therefore,methods for predicting the noise emitted by an applicationincluding one or several fans are desirable in order toimprove, accelerate and reduce the cost of low-noise design.The Noise Shaping Technology (NST) has been developed withinthe EC-project NABUCCO in order to fulfil the aboverequirements on a prediction method. According to NST, thenoise source (not necessary a fan) is described by one orseveral noise descriptors, CSSs, and the correspondingtransmission paths through the structure described by one orseveral transfer functions, ACFs. In this thesis, theapplicability of NST is evaluated on a cabinet for electronicequipment where small axial cooling fans constitute the primarysources of the airborne sound.</p><p>As an axial fan is a complex source of sound,simplifications are necessary when modelling its acousticproperties. Therefore, the sound radiation of an axial fan infree space was examined by expanding the generated soundpressure field into spherical harmonics. The conclusion on asource model for the cabinet example, where the fans are moreor less In-duct mounted, is a modified single axial dipole. Themodel is expected to be valid in the entire frequency range ofinterest except in the mid-frequency range where the modaldensity is low. In order to improve the source model in thisfrequency range, a future model based on a rotating dipole isproposed.</p><p>The sound power of a small axial fan is measured in an ISO10302 test-rig. In order to take account of flow conditions,acoustically transparent ducts have been developed. These shallbe attached to the test-rig when measuring the sound power ofthe fan. A simple but practical method of how to correct thesound power for the baffling effect of the test-rig has alsobeen developed. Finally, the sound power can be converted intodipole force, which is the airborne CSS corresponding to thesingle axial dipole model.</p><p>The corresponding airborne transfer function (ACF), i.e.,from dipole force at the source point to sound pressure at thereceiver point, is measured reciprocally by taking use ofLyamshevs reciprocity relation.</p><p>From multiplication of the CSS and the ACF, the soundpressure can be predicted. The prediction shows quite goodagreement with the measured values.</p><p><b>Keywords:</b>axial fan, airborne sound, sourcecharacterisation, transmission path analysis, In-duct,spherical harmonics, rotating dipole, installation effects, ISO10302, flow conditions, baffling effect, acousticallytransparent ducts, Lyamshevs reciprocity relation, reciprocity,CSS, ACF, GSM, NST.</p>

The optical design for a dual modality endoscope based on piezo scanning fiber technology is presented including a novel technique to combine forward-viewing navigation and side viewing OCT. Potential applications include navigating body lumens such as the fallopian tube, biliary ducts and cardiovascular system. A custom cover plate provides a rotationally symmetric double reflection of the OCT beam to deviate and focus the OCT beam out the side of the endoscope for cross-sectional imaging of the tubal lumen. Considerations in the choice of the scanning fiber are explored and a new technique to increase the divergence angle of the scanning fiber to improve system performance is presented. Resolution and the necessary scanning density requirements to achieve Nyquist sampling of the full image are considered. The novel optical design lays the groundwork for a new approach integrating side-viewing OCT into multimodality endoscopes for small lumen imaging.

Approved for public release, distribution is unlimited / A study of the performance of the Coupled Ocean Atmosphere Mesoscale Prediction System (COAMPS) was performed based on collected METOC properties affecting radar propagation during the Roughness and Evaporation Duct (RED) experiment conducted off the windward coast of Oahu, HI. The measured refractivity influencing parameters (SST, air temperature, humidity, and wind speed) were compared to COAMPS predicted values. Using the NPS bulk evaporation duct model, profiles of the modified refractivity were computed from the buoy data and compared to profiles computed from the COAMPS data. The profiles were obtained concurrently with S-Band propagation measurements along a 26-km path. The radar propagation predictions created by APM from the modified refractivity profiles, derived from the measured METOC values and COAMPS modeled values, were compared to the in situ measured propagation losses. The mean RMS error of the prop loss predictions derived from the COAMPS forecasted METOC values was <4 dB compared to a mean RMS error of <3 dB from the in situ measurement derived prop loss predictions. Significantly larger errors occurred at the COAMPS analysis times. Overall, the results are very promising for this trade wind region, where the air is cooler than the relatively warm sea surface. / Lieutenant, United States Navy

As células derivadas de fígado embrionário tanto de animais quanto de humanos tem sido cada vez mais estudas devido ao seu potencial antiinflamatório, imunomodulador e regenerativo, demonstrado as mesmas bipotencial de diferenciação em hepatócitos e colangiocitos. Na presente pesquisa utilizou-se células derivadas de fígados embrionários de ratos com 14,5 dias de gestação. As células apresentaram marcadores de células progenitoras hepáticas, bem como marcadores de células hepáticas e biliares diferenciadas confirmando, seu bipotencial. A terapia celular utilizando as células supracitadas, reduziu significativamente a progressão da fibrose hepática, diminuindo a inflamação e ainda estimulando a regeneração hepática de ratos submetidos à cirrose por ligadura do ducto biliar. As análises realizadas mediante avaliação quantitativa pela técnica de morfometria, demonstraram redução da deposição de fibras de colágeno, bem como menor proliferação de ductos biliares nos animais tratados. Os resultados foram ainda complementados por analise semiquantitativa, a qual avaliou a intensidade da necroinflamação dos tecidos hepáticos analisados, apontando menor escore de inflamação dos animais tratados. As células poderão ter efeito benéfico para o tratamento de doenças hepáticas crônicas, que estimulam a formação de fibrose. A cirrose é o estágio final comum à doenças hepáticas crônicas por causadas por fatores de diversas etiologias. Esta ocupa a decima quarta causa mundial de mortalidade em humanos, sendo que o único tratamento definitivo atualmente é transplante do órgão. Entretanto o número de transplantes está longe de suprir a demanda atual, visto que há um déficit de doadores do órgão. Terapias que possam oferecer uma alternativa de tratamento confiável, segura e acessível são bastante oportunas. Nossos resultados sugerem que as células utilizadas neste trabalho podem modular a fibrogênese, e consequentemente retardar o estabelecimento da cirrose em doenças hepáticas crônicas. / Studies on human and animal embryonic liver stem cells have been growing due to its anti-inflammatory, immunomodulatory and regenerative potential. These cells show also a bipotential do differentiate into hepatocytes and cholangiocytes. In the present study, it was used rodent embryonic liver with 14.5 of gestation. The cells presented hepatic progenitor, as well adult hepatic and biliary cells markers, confirming their bipotential. Previous studies with these cells in therapy decreased hepatic fibrosis progression in rat models submitted to cirrhosis by biliary duct ligation. Quantitative analysis was performed by morphometry showed decreased collagen fibers deposition and lower proliferation of biliary ducts in treated animals. Results were complemented with semiquantitative analysis with evaluation of necroinflammation of the analyzed hepatic tissues, in which a decreased inflammation score was observed. Cirrhosis is a common final stage for chronic hepatic diseases caused by different factors in several etiologies. It occupies the 14th world cause of mortality in human. However, the number of liver transplants is insufficient for current demand, caused by deficit in organs donors. Therapies that could offer an alternative for a reliable, safe and accessible treatment is opportune. Our results suggest that cells used in this study can modulate fibrogenesis and consequently delay the establishment of cirrhosis in chronic liver diseases.

A ema (Rhea americana americana) é uma ave que pertence ao grupo das Ratitas, ordem Rheiforme e a família Rheidae. Neste trabalho foram analisadas as características morfológicas, macroscópicas e microscópicas, dos órgãos do aparelho reprodutor masculino (testículos, epidídimos, ductos deferentes e falo) e a cloaca em 23 emas, quatro filhotes com duas semanas, sete jovens (de três a oito meses) e doze adultas (três anos), provenientes do abatedouro da Cooperativa Emas do Brasil, RS e do CEMAS, Mossoró, RN. Fragmentos de cada órgão foram fixados por imersão em formoldeído 10%, tampão fosfato pH 7,4, 0,1M ou em solução de Karnovsky (paraformoldeído 4% e glutaraldeído 2,5%, tampão fosfato pH 7,4, 0,1M) e processados na rotina para microscopia de luz e eletrônica de varredura, respectivamente. Os testículos da ema possuem formato alongado e localizam-se na cavidade celomática, na região intra-abdominal dorsal, com comprimento e largura médias de 7,6 ± 1,2 cm e 2,6 ± 0,7 cm nos adultos; 4,5 ± 1,5 cm e 0,9 ± 0,4 cm nos jovens; e 0,8 ± 0,3 cm, e 0,2 ± 0,1 cm nos filhotes. O testículo está envolto pela túnica albugínea e seu parênquima possui túbulos seminíferos, compostos por epitélio espermatogênico e por células de sustentação, e pelo tecido intersticial, com as células endócrinas intersticiais, tecido conjuntivo frouxo e vasos. Nos adultos observaram-se todas as células da linhagem espermatogênica, enquanto nos jovens com 3 meses os testículos apresentaram túbulos seminíferos com luz reduzidas, espermatogônia e células de sustentação indiferenciadas. O epidídimo apresentou-se alongado e fusiforme junto a margem medial do testículo. Os ductos eferentes possuem um epitélio pseudoestratificado colunar ciliado baixo, enquanto no ducto epididimário o epitélio é alto. O ducto deferentes apresentou trajeto sinuoso nos adultos, retilíneo nos jovens, convoluto na sua porção média, diminuindo seu formato sigmóide em sua porção caudal, próximo à cloaca. O epitélio é pseudoestratificado reveste a luz irregular nos adultos, e circular nos jovens, mantendo proximidade com o ureter. A cloaca dividiu-se em três segmentos: o coprodeu, o urodeo e o proctodeo. No urodeu os ductos deferentes desembocaram em papilas na parede ventro-lateral, próximo a inserção do falo fibroso. O falo é um órgão fibroso linfático, localizado na parede ventral, no assoalho da cloaca, e apresentou duas porções: uma rígida bifurcada e contorcida, e outra simples espiralada e flexível, a qual normalmente esteve invertida. De forma geral os órgãos reprodutores das emas compartilharam da morfologia de outras aves, principalmente aquelas descritas para os avestruzes. / The ema (Rhea american american) is a bird that belongs to the group of the Ratitas, order Rheiforme and family Rheidae. At this study were analyzed the morphological characteristics, macroscopic and microscopic, of the male genital organ (testes, epididymis, deferent ducts, and fhallus) and the cloaca in 23 emas, four chicken (two weeks old), young witer three to ten months old and twelve adult animals (three years old), originating from Cooperativa Emas do Brasil, RS and also from CEMAS, Mossoró, RN. Slices from each organ were fixed by immersion in phorformaldehyde 10%, or in Karnovsky solution (phorformaldehyde 10%, buffer phosphate pH 7.4, 0.1M and glutaraldehyde 2.5% buffer phosphate pH 7.4, 0.1M) and processed for light and scanning microscopy, respectively. The testis of rhea had elongated shape and were located inside coelomatic cavity, in dorsal region of abdominal cavity, with medium length and width of 7.6 ± 1.2 cm and 2.6 ± 0.7 cm at adult animals; 4.5 ± 1.5 cm and 0.9 ± 0.4 cm at young animals; and 0.8 ± 0.3 cm, and 0.2 ±0.1 cm at chicken. The testis were recovered by the tunica albuginea and its parenchyma had seminiferous tubules composed by spermatogenic epithelium and by sustentation cells, and also interstitial tissue, with interstitial endocrine cells, connective tissue and vessels. At the adult animals were observed all the cells from spermatogenic lineage, whilst at the youngs with 3 months the seminiferous tubules had a smale lumen with spermatogonia and undifferentiated sustentacular cells. The epididymis was elongated and fusiform closely to medial testis board. The efferents ductus were composed by a low ciliated pseudoestratified epithelium, while the epididimydis duct had a light epithelium. The deferent duct had sinuous stretch at adult animals, rectilineae at young animal, convolute at its medium portion, decreasing its sigmoid shape at caudal portion, next to cloaca. The epithelium was pseudostratified ciliated, irregular lumen at adult animal, and circular at young animal, closely with urether. The cloaca was divided into three segments: coprodeum, urodeum and proctodeum. At urodeum the deferent ducts discharged into papillas at the ventral side wall, next to fibrous phallus`s insertion. The phallus was a lymphatic fibrous organ, located at ventral wall, at the cloaca floor, and was composed by two portions: one rigid forked and twisted, and another simple spiraled and flexible, which normally was inverted. In a general way the Rhea genital organs shared the morphology from others birds, mainly those described to the ostrich.