Glass Reinforced Polymer pipes, commonly used in water transport applications, are prone to long term weepage. Weepage is defined as the transfer of fluid through the pipe and is considered a functional failure. An experimental investigation of weepage in multi-layered GRP pipes was carried out in two parts aiming to understand the phenomenon to help enhance the weepage resistance of manufactured pipes. First, liner surface profilometry investigation was carried out to identify microscopic features that might serve in initiating weepage. Second, MRI and x-ray tomography and SEM imaging of pipe samples aged with water and dye penetrant was carried out to capture weepage development through the pipe thickness. Diffusion through liner fiber/resin interface, propagation in the direction of poorly wetted hoop fibers and transverse cracks were found to be the likely causes of accelerating weepage in the samples. Fiber rich zones in the liner were considered weak spots that water can use for fast penetration of the liner. Finally, polyester netting used to hold core layer was found to help in water accumulation and transport through the pipe increasing the chances of failure.

lass fibre reinforced plastic (GRP) structural profiles, in standard shapes and sizes are now being commercially manufactured by the process of pultrusion. GRP profiles are light weight, posses higher specific strengths and are more durable than the conventional metal or concrete counterparts. GRP pultruded profiles have open or closed cross-sections comprising thin composite walls of low elastic moduli. Stability failure has been identified as the main cause of failure for these profiles when subjected to compressive stresses, as it may occurs at stresses much lower than the ultimate strengths. Therefore, the load carrying capacities of composite compression members mainly depends upon stability criteria. The conventional stability analyses for the prediction of buckling loads are not considered adequate as the GRP material is orthotropic and its behaviour is different from steel (non-yielding). The existing guidance for the design of composite members under compression ignores the presence of geometrical imperfections inherited in the pultruded profiles, whilst, experimental evidence suggests considerable loss of stiffness due to the imperfections particularly in the intermediate column heights. The design guidance provided by the manufacturers gives empirical equations based on data obtained from experiments on specified profiles. A universal design curve based on the experimental results of concentrically loaded GRP columns has been developed and presented. However, conducting a vast experimental study is not always feasible. The need to develop a procedure, predicting failure load numerically for the development of a design curve for GRP columns has been recognised. Two GRP box-sections (closed square cross-sections) have been investigated for failure/buckling loads using experimental and numerical methods. In the experimental phase, specimen columns of various heights have been concentrically loaded in compression to measure the failure loads. Experimental results have been compared with the theoretical predictions made using classical methods and the equations given by the design manuals. Based on the experimental and analytical failure loads, an experimental design curve has been derived. In the numerical study, 3-dimensional full scale finite element models representing experimental configuration of the composite columns, have been analysed using both linear and nonlinear solutions. Imperfections of known amplitudes have been included parametrically to establish the sensitivity of the failure loads towards imperfections. Imperfect model have been calibrated for the estimation of imperfection amplitude present in the profiles using experimental data. Using the numerical and analytical data, a design curve has been derived establishing interaction coefficients for each profile. The numerical design curve is compared with the experimental design curve for the validation of the numerical procedure adopted in this study. Effects of perforations (circular holes) on the buckling stiffness of GRP box-section columns have also been investigated. Holes are drilled in the walls of profiles and tested experimentally to measure the loss in the buckling loads. Finite element models of columns with holes have been developed and analysed for buckling loads. Comparisons of experimental and numerical results are plotted. For use in the numerical representation of the composite columns, mechanical properties of the orthotropic GRP material of the both sections have been established analytically and experimentally. In-plane shear properties have been measured by physically testing standard sized coupons, extracted along the length of profiles. However, short coupons were available in the transverse directions due to dimensional constraints. Short coupons, similar in geometry to the standard coupon, but smaller in size, have been validated for performance using finite element analyses and comparing the outcomes with the models of standard coupons. Both standard and short coupons have been used for the experimental measurement of the in-plane shear properties. Compression properties have also been measured experimentally. Ultimate failure/buckling loads of the composite columns depend upon their heights, material properties, and the cross-sectional dimensions. These factors have been combined into one characteristic parameter 'λ', the slenderness ratio. As the later two factors are constant for a particular box-section profile, the ultimate loads depend upon column heights. Four types of failure modes; global, local, modal interaction and material failure have been observed. The loss in the buckling stiffness is minimal for smaller circular holes, provided the interval between holes is not less than 20 times the diameter of the holes. For bigger holes and an inter hole spacing of 10time the diameter, a loss of 30% have been measured. Finite element representation of pultruded columns adequately predicted the numerical failure loads and failure modes for most of the column heights.

The research study determines OPNET simulation to evaluate the MANET routing protocols i.e. AODV, DSR, GRP and OLSR performance for HTTP and FTP base application traffic. Results from the simulation result helps to measure the performance matrix i.e. packet delivery fraction, normalized routing load, throughput and end to end delay. Scalar values are extracted from simulation to plot desired performance graphs to analyze. The research results and conclusion produces enough information for the selection of best routing protocol for MANET in terms of HTTP and FTP application types.

Submitted by PPG Biologia Celular e Molecular (bcm@pucrs.br) on 2017-07-24T18:23:29Z No. of bitstreams: 1 RAFAEL_SANGUINETTI_CZEPIELEWSKI_TES.pdf: 5487109 bytes, checksum: 88dbb99b9597e08253e2832cc01ccfce (MD5) / Approved for entry into archive by Caroline Xavier (caroline.xavier@pucrs.br) on 2017-07-25T17:50:46Z (GMT) No. of bitstreams: 1 RAFAEL_SANGUINETTI_CZEPIELEWSKI_TES.pdf: 5487109 bytes, checksum: 88dbb99b9597e08253e2832cc01ccfce (MD5) / Made available in DSpace on 2017-07-25T18:00:09Z (GMT). No. of bitstreams: 1 RAFAEL_SANGUINETTI_CZEPIELEWSKI_TES.pdf: 5487109 bytes, checksum: 88dbb99b9597e08253e2832cc01ccfce (MD5) Previous issue date: 2016-03-18 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / Tumor microenvironment and inflammatory diseases promote alterations in our immune system along with their development. Several molecules are implicated in this modulation and are therefore considered therapeutic targets. Gastrin-releasing peptide (GRP) is produced in tumors where it promotes cellular proliferation. It is also correlated with chronic diseases, as in rheumatoid arthritis and asthma, and in the acute condition of sepsis. Recently, our group found a direct GRP action over neutrophils, promoting migration. This work aimed to study the interface between GRP-producing tumors and the recruitment of immune cells, as well as extend the cellular studies about neutrophil activation and migration processes promoted by the peptide. In tumors, we observed that a lung adenocarcinoma cell line does not proliferate in response to GRP. Yet, it is induced to migrate when exposed to the peptide, indicating a potential role for GRP in metastasis of this type of cancer. In our tumor immunology studies, we established a novel in vivo model by overexpressing GRP in a melanoma cell line (B16F10). We observed the augment of infiltrating inflammatory monocytes in the tumor microenvironment of these tumors. In parallel, we verified that reactive oxygen species production and migration in response to GRP is dependent of the NADPH oxidase complex. GRP stimulation promotes an intense activation, which culminates in neutrophil extracellular traps (NETs) release. In addition, the GRP receptor (GRPR) antagonist RC-3095 presented anti-inflammatory potential, inhibiting neutrophil migration towards IL-8 and reducing the extent of acetaminophen-induced liver damage. This effect was due to motility alterations in infiltrating neutrophils within the tissue and reduction of cell adhesion molecules. The results presented herein demonstrate the wide panorama of GRP?s interactions in tumor and immune biology. / O microambiente tumoral e as doen?as inflamat?rias promovem altera??es nas c?lulas do nosso sistema imune ? medida que progridem. Diversas mol?culas est?o envolvidas nessa modula??o, e por isso s?o alvos terap?uticos. O pept?deo liberador de gastrina (GRP) ? produzido por tumores, onde promove prolifera??o celular. Este tamb?m est? correlacionado com doen?as cr?nicas como a artrite reumatoide e asma, e em doen?as agudas, como a sepse. Recentemente, nosso grupo descobriu a??o direta do GRP em neutr?filos, promovendo indu??o de migra??o. O presente trabalho se prop?s a estudar a interface entre tumores produtores de GRP e o recrutamento celular, assim como aprofundar os estudos celulares sobre os processos de ativa??o e migra??o de neutr?filos promovidos pelo pept?deo. Em tumores, observamos que uma linhagem de adenocarcinoma pulmonar n?o prolifera quando exposto ao GRP, por?m ? induzida a migrar quando exposta ao pept?deo, estabelecendo um potencial papel deste na promo??o de met?stases para esse tipo tumoral. Na interface da imunologia tumoral, atrav?s do desenvolvimento de um modelo in vivo de superexpress?o de GRP em melanoma murino (B16F10), observamos que esse aumento do GRP induz a infiltra??o de mon?citos inflamat?rios no microambiente tumoral. Em paralelo, verificamos que a produ??o de esp?cies reativas de oxig?nio e a migra??o em dire??o ao GRP s?o dependentes do complexo NADPH oxidase. Esse est?mulo promove ativa??o intensa, culminando na produ??o de redes extracelulares de neutr?filos (NETs). J? o antagonista do seu receptor, GRPR, apresentou potencial antiinflamat?rio, sendo capaz de inibir a migra??o neutrof?lica via modula??o de IL-8 e reduzindo a extens?o da les?o hep?tica induzida por paracetamol (acetaminofeno), alterando a motilidade dos neutr?filos no tecido e a express?o de mol?culas de ades?o. Assim, os resultados aqui apresentados demonstram um panorama amplo da fun??o do GRP na biologia tumoral e no sistema imune.

本文提出ERP在政府部門運用的研究目的，主要是希望在當今電子商務蓬勃發展的環境中，藉由ERP（Enterprise Resource Planning）－企業資源整體規劃之理念，提出GRP（Government Resource Planning）－政府機關整體資源規劃模式及概念，並以「外勞動態管理」為例子，提出外籍勞工管理業務如何橫跨部會機關組織範疇的水平整合與層級的垂直整合，進行全面性作業流程與資訊分享的統合，促進外籍勞工資料供應鏈之整合運作，以做為政府再造之參考。 本文除針對此觀念實務探討，亦針對目前政府機關再推動電子資料交換時的網路架構與模式提出意見，最後並提出一適合作為GRP電子資料交換之網路架構，希望經由此整合架構，對政府機關順利推動GRP時做出適當之貢獻。

Molecular Imaging provides new aspects in cancer diagnosis and treatment. With the ap-plication of imaging and biological techniques, molecular imaging can monitor molecular and cellular changes of different diseases. To interpret the mechanism of disease, more and more at-tention is focused on the development of new probes for molecular imaging. Magnetic resonance imaging (MRI) is a powerful, non-invasive clinical diagnostic tool with high spatial resolution without the limitation of the depth of tissues. Applications of MRI contrast agents can amply the MRI signal during imaging. Many studies have been devoted to developing targeted MR contrast agents. Proteins and peptides have been widely used for target-ing cancer cells in cancer diagnosis and treatments. GRP, gastrin-releasing peptide, is one of a well-characterized group of mammalian bombesin-like peptides. GRP acts through its cell surface receptors, GRP receptor (GRPR). It has been reported that there is a high density of GRP receptors in the majority of prostate carci-noma. In contrast, the GRPRs are not highly expressed in normal cells of most tissues. Thus, this tumor specific expression pattern provides an advantage for cancer targeting. A novel class of MRI contrast agent was designed by adding the Gd3+ binding sites into a stable host protein, the domain 1 of rat CD2. Due to the unique features of the designed metal binding properties, the protein contrast agent (ProCA1) exhibits more than 10-fold enhanced MRI relaxivity compared to that of the more commonly used Gd-DTPA. The high relaxivity of the designed protein contrast agent largely overcomes the major barrier of low sensitivity of MRI techniques. A peptide of ten amino acids from the C-terminal of GRP was grafted onto ProCA1. GRP-grafted protein contrast agents (ProCA1.GRPs) showed the targeting capability to the GRPRs which are over-expressed on prostate cancer cells. Cell MRI Imaging demonstrated that ProCA1.GRP(52) grafted between Lys51 and Ser52 had better targeting capability than C-terminal one. Administration of ProCA1.GRP into xenograft tumor model enhances the contrast in the GRPR+ prostate tumor under MRI and optical imaging. Study demonstrated a potential application for disease marker targeted MR imaging by using our developed protein contrast agent.

臨床上止癢藥物的發展有限,故尋找具有廣泛止癢效果的藥物及探討癢覺傳遞的 神經受體機制是相當重要的。從過去研究中發現,bombesin 能在嚙齒類動物引發強 烈的搔抓行為。另外,bombesin 對 bombesin receptor family 中的 gastrin- releasing peptide receptor(GRPr)和 neuromedin B receptor(NMBr)也有高度親 和力。本研究主要目的為釐清 GRPr 和 NMBr 是否具有獨立調控癢覺搔抓行為的能 力。藉由側腦室於大白鼠中樞給藥並量化大白鼠的後肢搔抓行為,建立 GRP 與 NMB 這兩種胜肽在大白鼠上引發搔抓行為的基本藥理特性,並透過 GRPr 與 NMBr 這兩種受體的專一性拮抗劑探討受體間對於調控癢覺搔抓行為的獨立性。透過每天連 續施打 bombesin、GRP 與 NMB 這三種胜肽探討大白鼠搔抓行為的耐受性及三種胜 肽引發之搔抓行為在長時間觀測上的比較。最後,利用 GRPr 與 NMBr 這兩種受體 的專一性拮抗劑來探討 bombesin 引發搔抓行為的機制。利用側腦室給予 GRP (0.03 - 0.3 nmol)與 NMB(0.1-1 nmol)皆引發劑量相關性的搔抓行為反應。GRPr 的拮抗劑 RC-3095 (0.1-1 nmol)可以劑量相關性地阻斷 GRP 所引發的搔抓行 為,但不能阻斷 NMB 所引發的搔抓行為。相對而言,NMBr 的拮抗劑 PD168368 (0.3-3 nmol)可以劑量相關性地阻斷 NMB 引發的搔抓行為,但不能阻斷 GRP 所引 發的搔抓行為。藉由這些拮抗劑實驗,証實了 GRPr 與 NMBr 兩受體皆調控癢覺的訊 息傳遞並獨立不互相影響。Bombesin、GRP 與 NMB 都能引發搔抓行為,但程度與 持續時間上都有差異。但是每天施打這三種胜肽皆引發搔抓行為的耐受性。然而, RC-3095 與 PD168368 的有效劑量或兩個拮抗劑的組合並不能阻斷 bombesin 所引 發的搔抓行為,意指 bombesin 所引發的搔抓行為可能由其他受體調控。由本研究得 知,GRPr 與 NMBr 分別獨立調控中樞神經系統的癢覺訊息傳遞,並有程度與持續時 間上的差異。更重要的是,綜合先前文獻研究讓我們瞭解 bombesin-recognized neurons 中還有其他重要的受體機制調控於中樞神經系統的癢覺傳遞。 / Bombesin is a pruritogenic agent that causes intense itch-scratching activity in rodents. Bombesin has high affinity for the gastrin-releasing peptide receptor (GRPr) and the neuromedin B receptor (NMBr). The aim of this study was to investigate pharmacologically the ability of GRPr and NMBr to themselves elicit scratching behavior in rats. The intracerebroventricular (i.c.v.) route was selected for drug delivery because the study focused on supraspinal sites of action. The magnitude and duration of scratching produced by the naturally occurring peptides GRP and NMB were characterized. Antagonists selective for GRPr (RC-3095) and NMBr (PD168368) were used to define the role of GRPr and NMBr in the scratching response. After i.c.v. administration, GRP (0.03-0.3 nmol) and NMB (0.1-1 nmol) dose-dependently elicited marked scratching. There was a tolerance to scratching elicited by daily repeated administration of bombesin, GRP, or NMB. Presession administration of RC-3095 (0.1-1 nmol) and PD168368 (0.3-3 nmol) dose- dependently antagonized scratching elicited by GRP and NMB, respectively. More important, 1 nmol of RC-3095 failed to block NMB- elicited scratching and 3 nmol of PD168368 failed to block GRP-elicited scratching. In addition, pretreatment with effective doses of RC-3095 or PD168368 alone or in combination did not block bombesin-elicited scratching. Through the use of the selective antagonists RC-3095 and PD168368, this study demonstrates that central GRPr and NMBr may act independently to elicit scratching behavior. Although the receptor mechanisms underlying bombesin-elicited scratching elude us, this study provides a pharmacological basis for GRPr and NMBr antagonists as potential antipruritics.

1. Large rivers in the central United States experience a variety of ecological interactions. Both short- and long-term temporal changes affect both fish and zooplankton communities in rivers. Variation in diel patterns of predation could affect differences of behavior in prey. Long term temporal changes across seasons can lead to different areas of rivers providing growth or costing energy. Spatial changes also affect habitat quality and behaviors of the aquatic organisms within large rivers. Spatial variation can be dynamic and occur between longitudinally connected habitats or vary through different sections of the reach and can also change seasonally. 2. Invasive species have major economic and ecological impacts. In aquatic ecosystems, plankton are the base of the food web and a planktivore invader can cause major ecological disruptions. The Wabash River is a large free flowing river with a variable hydrology, which causes dramatic changes in habitat availability through time. Therefore, habitat usage, quality, and availability may differ for native and invasive species through time. The objectives of this study were to assess how habitat quality changes in a large, flashy, free-flowing river over time, and to compare the quantity and overlap of quality macrohabitat for invasive and native fish. Growth rate potential (GRP) was used to quantify habitat quality for Silver Carp (Hypophthalmichthys molitrix; invasive) and Gizzard Shad (Dorosoma cepedianum; native). To calculate GRP, bioenergetic models were used with monthly observations of food abundance (zooplankton, phytoplankton, and detritus), water temperature, dissolved oxygen, and water velocity of various habitat types from the Wabash River’s confluence with the Ohio River upstream to Terre Haute, Indiana, approximately 215 river miles. Negative GRP for both Silver Carp and Gizzard Shad occurred during spring and most of summer. However, in the fall, the majority of the river had a positive GRP for both species. Reduced flows and increases in food abundance were the cause for the switch from negative to positive GRP. There was a high degree of spatial overlap in positive GRP areas between Silver Carp and Gizzard Shad, suggesting that there is a high degree of competition. Acoustically tagged Silver Carp selected for areas predicted to have a positive GRP from the model presented in the study. This model showed that regulation of flows in hydrologically altered systems could potentially lower the impact of Silver Carp in those systems. With Silver Carp selecting for predicted habitats, a bioenergetics model can be used to inform commercial fishers where to focus effort to maximize catch.3. Temporal changes in rivers tend to be quantified at broad seasonal scales. However, river conditions including water flow, water temperature, dissolved oxygen, and availability of zooplankton prey may change daily. In large rivers, these conditions may change in a diel fashion between backwater and main channel habitats. To assess diel changes in the Illinois River, zooplankton, paired with mobile hydroacoustic surveys for fish were sampled from three main channel and three off-channel sites in the LaGrange reach every four hours in a twenty-four-hour period at different depths between October 22 and 26, 2018. Water depth, water temperature, water velocity, and fish (planktivore and nonplanktivore) densities were quantified during each sampling time. Water temperature and water velocity differed between the two habitat types. Water temperature was higher and water velocity was lower in the off-channel. Water temperature was colder in the morning in both the main channel and off-channel. Water velocity did not change throughout the day. The majority of the zooplankton community was comprised of rotifers which were less mobile than larger taxa and did not migrate. When evaluating the more mobile, large body zooplankton, time and depth affected copepod density in off-channel environments, where the deeper depth had a higher copepod density than the shallower depth. In contrast, only time of day affected off-channel cladoceran density, where densities increased at night. Fish did not exhibit diel patterns and the off-channel habitat had a higher density. The most likely mechanism behind the diel movements of the large bodied zooplankton was predation by planktivorous fish. The present study suggests that connections to the off-channel habitats in large rivers will promote quality habitat for both zooplankton and fish.

No description available.

La surexpression des récepteurs GRP au niveau de différents types de cancers communs offre la possibilité d'utiliser des analogues radiomarqués de la bombésine pour leur diagnostic et leur traitement. Ce travail de thèse est consacré à la conception, la synthèse et l'évaluation biologique de nouveaux radiopharmaceutiques, contenant un antagoniste des récepteurs GRP, un bras espaceur et le chélatant cyclique DOTA. Nous avons tout d'abord déterminé la longueur du bras espaceur permettant une optimisation des propriétés biologiques. Puis en se basant sur les résultats de cette étude nous avons réalisé la synthèse et l'évaluation biologique de radio-ligands constitués d'antagonistes originaux des récepteurs GRP. Ces antagonistes ont été conçus en se basant sur le composé JMV 594, un antagoniste puissant de la bombésine synthétisé dans notre laboratoire. En plus de modifications réalisées sur ce peptide, des dimères ont également été synthétisés de façon à obtenir des antagonistes plus stables et plus affins pour les récepteurs GRP. / The abundant expression of the GRP receptor in many frequently occurring cancers that inflict humans provides the opportunity to use radiolabeled bombesin analogs for their diagnosis and treatment. This postgraduate work is dedicated to the design, synthesis and biological evaluation of new radiopharmaceuticals. These are made up of a GRP receptor antagonist, a spacer and the cyclic metal chelating agent DOTA. We first determined the spacer length which has optimal biological properties. Moving forward from this study, different radio-ligands containing new bombesin antagonists have been synthesized and biologically evaluated. Those antagonists are based on compound JMV 594, a powerful bombesin antagonist synthesized in our laboratory. Besides modifications of this peptide also dimers have been made to obtain more stable bombesin antagonist with more affinity to the GRP receptor.