Amylin, a 37 amino acid peptide secreted from pancreatic beta cells upon stimulation by meal/glucose, belongs to the family of the calcitonin or calcitonin gene-related peptide (CGRP) and shares up to 50% homology with CGRP, which is a well-documented pain-related peptide. The amylin receptor is composed of a calcitonin receptor (CTR) and receptor activity modifying proteins (RAMPs). Numerous studies have shown that amylin plays an important role in glucose homeostasis and food intake. Few studies have been conducted with respect to the effect of amylin in the central or peripheral neuraxis. In this thesis, immunohistochemical study revealed a dense network of amylin-immunoreactive (irAMY) cell processes in the superficial dorsal horn of the mice. Numerous dorsal root ganglion and trigeminal ganglion cells expressed moderate to strong irAMY. Reverse transcriptase-polymerase chain reaction (RT-PCR) revealed amylin receptor mRNA in the mouse spinal cord, brain stem, cortex, hypothalamus and hippocampus. The nociceptive or antinociceptive effects of amylin were evaluated in the tail flick and acetic acid-induced writhing test. Amylin (1-10 µg, i.t.) reduced the number of writhing in a dose-dependent manner. Pretreatment of the mice with the amylin receptor antagonist salmon calcitonin (8-32) [sCT(8-32)]or AC187 by i.t. antagonized the effect of amylin on acetic acid-induced writhing test. Locomotor activity was not significantly modified by amylin injected either i.p. (0.01-1 mg/kg) or i.t. (1-10 µg). Measurement of c-fos mRNA by RT-PCR or proteins by Western blot showed that the levels were up-regulated in the spinal cord of mice in acetic acid-induced visceral pain model and the increase was attenuated by pretreatment with amylin. Pretreatment of sCT[8-32] or AC187 significantly reversed the effect of amylin on c-fos expression in the spinal cord. As the neuronal response to amylin is closely dependent on the molecular property of amylin receptor, the localization, internalization and regulation of the calcitonin and amylin receptor were examined in the second part of the thesis. Immunofluorescence microscopy demonstrated the surface expression of CTRa, and intracellular distribution of RAMP1. Moreover, co-expression of CTRa translocated the RAMP1 to the cell surface and generated the amylin receptor phenotype. Both immunocytochemistry and on cell western analysis showed the internalization of CTRa and amylin receptor (CTRa/RAMP1) stimulated by different agonists, which was partially ß-arrestin dependent. Moreover, RAMP1 did not change the surface expression pattern of CTRa, but co-localized with the receptor with and without agonist treatment. sCT and amylin activated the ERK1/2 in HEK293 cells stably expressing amylin receptors, indicating the involvement of MAPK in amylin receptor signaling cascade. Collectively, these results led us to conclude that 1) irAMY is expressed in dorsal root ganglion neurons with their cell processes projecting to the superficial layers of the dorsal horn, and that the peptide by interacting with amylin receptors in the spinal cord may be antinociceptive; 2) RAMP1 does not change the pattern of CTR cell-surface localization and internalization, but receptor phenotype, presumably through a direct or indirect effect on the ligand-binding site; 3) amylin internalizes the amylin receptor (CTRa/RAMP1 complex); which is partially ß-arrestin dependent. Our studies extend the current knowledge of amylin on the spinal cord and new insight on the cellular and molecular mechanism underlying the antinociceptive effect of amylin. Also we demonstrate for the first time agonist induced-internalization of CTR/RAMP complex and its possible regulation pathway. / Pharmacology

Ramps are usually perceived as utilitarian objects emerging from standardized guidelines for architecture and landscape architecture. But closer examination reveals they can be quite beautiful and poetic. What we commonly call ramps, Galileo referred to as inclined planes, counting them as one of six classical simple machines in Le Meccaniche (On Mechanics) . Because inclined planes are actually static machines that do not require any energy to run. They do not discriminate among users. This thesis explores the work of the ramp in moving fragile loads, such as human beings. / Master of Landscape Architecture

An experimental investigation was conducted to compare the supersonic mixing performance between a novel aerodynamic ramp injector and a physical ramp injector. The aerodynamic ramp injector consisted of nine, flush-wall jets arranged to produce multiplicative fuel-vortex interactions for mixing enhancement in a supersonic main flow. The physical ramp injector was a previously optimized and tested swept-ramp design. Test conditions included a Mach 2.0 freest ream of air with a Reynolds number of 3.63 x 10⁷ per meter and helium injection with jet-to-freestream momentum flux ratios of 1.0 and 2.0. Planar-laser Rayleigh scattering and conventional probing techniques including species composition sampling were employed to interrogate the flow field at several downstream locations. Results show that with increasing jet momentum, the aero-ramp exhibited a significant increase in penetration while the physical ramp showed no discernible change. The near-field mixing of the aero-ramp was superior to that of the physical ramp. At the higher jet momentum, the far-field mixing of the aero-ramp was comparable to the physical ramp. In all cases, the total pressure losses suffered with the aero-ramp were less than those incurred with the physical ramp. For both injectors, the total pressure losses decreased with increasing jet momentum. Finally, an analytical relationship predicting the Rayleigh scattering intensity as a function of helium concentration, pressure, and temperature was derived and experimentally validated. It is concluded that these results merit further studies and parametric optimization of the aero-ramp or similar configurations. It is also concluded that further studies may be conducted to establish the absolute quantitative nature of the Rayleigh scattering technique. / Ph. D.

Este trabalho tem por finalidade desenvolver um método baseado em Otimização Topológica para projetar uma estrutura mecânica, chamada de sonotrodo, acoplada a um transdutor piezelétrico de potência (dispositivo mecânico capaz de transformar energia elétrica em deformação mecânica ou vice-versa). Um sonotrodo é uma estrutura utilizada para transmitir vibrações mecânicas de um transdutor piezelétrico, ajustando a amplitude e a distribuição dos deslocamentos gerados por essa vibração para obedecer aos requisitos do projeto do transdutor. Dentre as aplicações de transdutores piezelétricos utilizando sonotrodos, pode-se citar sonares para navegação, limpeza e solda ultrassônica, tomografia acústica, furadeiras ultrassônicas, corte ultrassônico de tecidos, etc. Os requisitos de projeto do sonotrodo variam para cada aplicação, desde a necessidade de se obter o deslocamento máximo em um único ponto do sonotrodo até a uniformização do deslocamento de um plano inteiro da estrutura. Para a obtenção do resultado ótimo, neste trabalho são aplicadas técnicas de Otimização Topológica (OT). OT é um procedimento para projetar o leiaute ótimo de estruturas distribuindo material dentro de uma região fixa. O método de OT é implementado utilizando a Programação Linear Seqüencial (PLS) como algoritmo de otimização, e é baseado na interpolação \"Simple Isotropic Material with Penalization\" (SIMP) como formulação de modelo de material. É apresentado também um estudo sobre a utilização do modelo de material \"Rational Approximation of Material Properties\" (RAMP) na tentativa de se reduzir instabilidades numéricas como modos localizados. O Método de Elementos Finitos (MEF) é aplicado para modelar o sonotrodo utilizando a formulação de elemento axissimétrico de quatro nós e de elemento em Estado Plano de Tensões Mecânicas (EPTM). É apresentada a implementação para OT estrutural contínua baseada em variáveis de projeto por nós, o que minimiza instabilidades numéricas, tais como \"instabilidade de tabuleiro\". As freqüências de ressonâncias e os modos de vibrar são computados através do método de Lanczos. É utilizado um algoritmo baseado na formulação \"Modal Assurance Criterion\" (MAC) para que um certo modo de vibrar seja encontrado, de modo que a freqüência de ressonância relacionada a esse modo seja otimizada. São apresentados exemplos para verificar a eficiência e a generalidade do método proposto, e também, um estudo sobre a influência dos parâmetros de otimização utilizadas no método. Por fim, são apresentados resultados que atendem a todos os requisitos de projeto, bem como seu pós-processamento, e análise no software comercial ANSYS®. / This work aims at the development of a method based on Topology Optimization to design a mechanical structure, called sonotrode, which is a device usually connected to a high power piezoelectric transducer (mechanical device capable of converting electric energy into mechanical displacement or vice-versa). A sonotrode transmits mechanical vibrations of a piezoelectric transducer, adjusting the amplitude and the distribution of these vibrations to fit the design needs of the transducer. Among applications of piezoelectric transducers using sonotrodes, we can cite navigation sonars, ultrasonic cleaning and melting, acoustic tomography, ultrasonic drilling, ultrasonic fabric cutting, etc. The design needs of the sonotrode differs for each application, ranging from obtaining maximum displacement in one single point of its structure, to obtaining uniform displacements on a whole face of the sonotrode. To improve the attainment of the optimum result, in this work \"Topology Optimization\" (TO) is applied to design the sonotrode. TO is a procedure to design the optimal layout of structures by distributing material within a fixed domain. The objective of the developed TO formulation is to find the best topology of the sonotrode that produces maximum and uniform displacements at one of its face. The TO method is implemented using the \"Sequential Linear Programming\" (SLP) as the optimization algorithm, and it is based on the \"Simple Isotropic Material with Penalization\" (SIMP) interpolation for material model formulation. It\'s also presented a study about the material model \"Rational Approximation of Material Properties\" (RAMP), in an attempt to reduce numerical instabilities like localized modes. \"Finite Element Method\" (FEM) is applied to model the sonotrode considering piezoelectric four-node axisymmetric elements. A node-based design variable implementation for continuum structural topology optimization is presented to minimize numerical instabilities such as \"checkerboard pattern\". The ressonance frequencies and modes are computed through Lanczos Method. A \"Modal Assurance Criterion\" (MAC) based formulation is used to track a certain mode, so that, the ressonance frequency related to this mode can be optimized. Examples are presented to verify the efficiency and the generality of the proposed method, and also, a study about the influence of the optimization parameters used in the method. Finally, results that meets all the design requirements are presented, as well as their post-processed topology, and the analysis in the commercial software ANSYS®.

Ramp metering is an effective management strategy, which helps to keep traffic density below the critical value, preventing breakdowns and thus maintaining the full capacity of the freeway. Warrants for ramp metering installation have been developed by a number of states around the nation. These warrants are generally simple and are based on the traffic, geometry, and safety conditions in the immediate vicinity of each ramp (local conditions). However, advanced applications of ramp metering utilize system-based metering algorithms that involve metering a number of on-ramps to address system bottleneck locations. These algorithms have been proven to perform better compared to local ramp metering algorithms. This has created a disconnection between existing agency metering warrants to install the meters and the subsequent management and operations of the ramp metering. Moreover, the existing local warrants only consider recurrent conditions to justify ramp metering installation with no consideration of the benefits of metering during non-recurrent events such as incidents and adverse weather. This dissertation proposed a methodology to identify the ramps to meter based on system-wide recurrent and non-recurrent traffic conditions. The methodology incorporates the stochastic nature of the demand and capacity and the impacts of incidents and weather using Monte Carlo simulation and a ramp selection procedure based on a linear programming formulation. The results of the Monte Carlo simulation are demand and capacity values that are used as inputs to the linear programming formulation to identify the ramps to be metered for each of the Monte Carlo experiments. This method allows the identification of the minimum number of ramps that need to be metered to keep the flows below capacities on the freeway mainline segment, while keeping the on-ramp queues from spilling back to the upstream arterial street segments. The methodology can be used in conjunction with the existing local warrants to identify the ramps that need to be metered. In addition, it can be used in benefit-cost analyses of ramp metering deployments and associated decisions, such as which ramps to meter and when to activate in real-time. The methodology is extended to address incidents and rainfall events, which result in non-recurrent congestion. For this purpose, the impacts of non-recurrent events on capacity and demand distributions are incorporated in the methodology.

Thesis (Ph.D.)--George Mason University, 2008. / Vita: p. 199. Thesis director: Roger Stough. Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Public Policy. Title from PDF t.p. (viewed Mar. 16. 2009). Includes bibliographical references (p. 182-198). Also issued in print.

Syftet: Syftet med denna studie är att kartlägga belastningsergonomiska risker i ett framtida internt logistikflöde, samt att ge förslag på hur dessa risker kan undvikas genom tillämpning av LEAN metodik och en ny logistiklösning. Följande frågeställningar har ställts för att identifiera orsaker till problem och förbättringsmöjligheter: 1)    Vilka arbetsmoment i det studerade logistikflödet leder till ergonomiska risker? 2)    Hur kan fallstudieföretaget införa LEAN metodik för att uppnå bättre ergonomi vid materialhantering? 3)    Hur kan en ny generell och mer ergonomisk logistiklösning för materialhantering se ut på fallstudieföretaget? Metod: Studien har genomförts baserat på en fallstudie på ett industriföretag. Data har samlats in genom intervjuer och observationer på fallstudieföretaget, studiebesök på två andra industriföretag samt genom en litteraturstudie. För att identifiera och bedöma olika ergonomiska risker har verktyget RAMP tillämpats. Studiens resultat: Studien resulterade i en ergonomisk kartläggning för ett utvalt internt logistikflöde med förslag på hur bättre ergonomi kan uppnås i fallstudieföretagets material-hantering. Den ergonomiska kartläggningen påvisade att flera arbetsmoment innebär en ökad risk för att personalen utvecklar belastningsbesvär. Många tunga lyft, skjuta- och dra arbete samt olämpliga arbetsställningar visades ha störst negativ inverkan på ergonomin. För att minska dessa risker utan större förändringar av nuvarande fabrikslayout och befintligt arbetsflöde kan bland annat arbetsrotation, olika hjälpmedel och modifieringar av teknisk utrustning införas. Förslag presenteras också på hur en ny och mer ergonomisk materialhanteringslösning kan se ut på fallstudieföretaget genom införande av en omplockningsstation och en supermarket. Även ett förslaget ramverk presenteras för hur fallstudieföretaget kan arbeta genom LEAN-metodik i syfte att uppnå en bättre ergonomi i materialhanteringen. Slutsats: Den ergonomiska kartläggningen indikerade att förbättringsåtgärder krävs för att personal inte ska riskera att utveckla belastningsbesvär och förslag har tagits fram för hur den ergonomiska situationen kan förbättras. Rekommendationer: Fallstudieföretaget rekommenderas att vidta åtgärder för de ergonomiska risker som har identifierats. Innan de föreslagna förbättringarna fullföljs krävs vidare studier för att utvärdera förbättringsförslagen ur andra än ergonomiska aspekter samt genomförande av RAMP-analys. Fallstudieföretaget rekommenderas även att undersöka möjligheten att införa det föreslagna LEAN-ramverket i syfte att skapa förutsättningar för en god ergonomisk situation. Nyckelord: Belastningsergonomi, RAMP, Omplockningsstation, Arbetsmiljö, Intern logistik, Materialhantering / Purpose: The purpose of this study is firstly to identify risks of ergonomic strain in a future internal logistics flow and secondly propose how to avoid these risks by applying LEAN methodology and a new logistics solution. In order to identify causes for problems and to find improvement opportunities the following issues have been addressed: 1)    What tasks in the studied logistics flow lead to risks of ergonomic strain? 2)    How can the studied company implement the LEAN methodology to improve ergonomics in the material handling? 3)    How can a new general and more ergonomic logistic solution for material handling look like for the studied company? Method: The study has been conducted based on a case at an industrial company. Data has been collected through interviews and observations at the company, visits at two other industries and through a literature survey. To identify and assess various ergonomic risks, the RAMP tool has been applied. Study result: The study resulted in an ergonomic survey for a selected internal logistics flow with suggestions on how to improve ergonomics in the studied company´s material handling. The ergonomic survey showed that several work tasks cause an increased risk for the operators to develop strain injuries and therefore improvements are required. Heavy lifting, pulling and sliding work pieces and incorrect working positions were shown to have the most adverse impact on good ergonomics. To reduce these risks - without major changes to the current factory layout and existing workflow - work rotation, various tools/aids and modifications of technical equip-ment can be implemented. Proposals are presented on how a new and more ergonomic material handling solution can be achieved at the studied company through the introduction of a pickup station and a “supermarket”. A suggested framework is also presented for how the company can use LEAN methodology in order to achieve better ergonomics in the material handling process. Conclusion: The ergonomic survey indicated that improvements are required in order not to risk strain injuries for the operators. Suggestions have been made for how the ergonomic situation can be improved. Recommendations: The studied company is recommended to take measures with respect to the ergonomic risks identified. Before the proposed improvements can be introduced, studies are required to evaluate the improvement proposals from other than ergonomic aspects as well as performing a RAMP analysis. The studied company is also recommended to investigate the possibility of introducing the proposed LEAN framework. Keywords: Strain ergonomics, RAMP, Picking station, Work environment, Internal logistics, Material handling

Este trabalho tem por finalidade desenvolver um método baseado em Otimização Topológica para projetar uma estrutura mecânica, chamada de sonotrodo, acoplada a um transdutor piezelétrico de potência (dispositivo mecânico capaz de transformar energia elétrica em deformação mecânica ou vice-versa). Um sonotrodo é uma estrutura utilizada para transmitir vibrações mecânicas de um transdutor piezelétrico, ajustando a amplitude e a distribuição dos deslocamentos gerados por essa vibração para obedecer aos requisitos do projeto do transdutor. Dentre as aplicações de transdutores piezelétricos utilizando sonotrodos, pode-se citar sonares para navegação, limpeza e solda ultrassônica, tomografia acústica, furadeiras ultrassônicas, corte ultrassônico de tecidos, etc. Os requisitos de projeto do sonotrodo variam para cada aplicação, desde a necessidade de se obter o deslocamento máximo em um único ponto do sonotrodo até a uniformização do deslocamento de um plano inteiro da estrutura. Para a obtenção do resultado ótimo, neste trabalho são aplicadas técnicas de Otimização Topológica (OT). OT é um procedimento para projetar o leiaute ótimo de estruturas distribuindo material dentro de uma região fixa. O método de OT é implementado utilizando a Programação Linear Seqüencial (PLS) como algoritmo de otimização, e é baseado na interpolação \"Simple Isotropic Material with Penalization\" (SIMP) como formulação de modelo de material. É apresentado também um estudo sobre a utilização do modelo de material \"Rational Approximation of Material Properties\" (RAMP) na tentativa de se reduzir instabilidades numéricas como modos localizados. O Método de Elementos Finitos (MEF) é aplicado para modelar o sonotrodo utilizando a formulação de elemento axissimétrico de quatro nós e de elemento em Estado Plano de Tensões Mecânicas (EPTM). É apresentada a implementação para OT estrutural contínua baseada em variáveis de projeto por nós, o que minimiza instabilidades numéricas, tais como \"instabilidade de tabuleiro\". As freqüências de ressonâncias e os modos de vibrar são computados através do método de Lanczos. É utilizado um algoritmo baseado na formulação \"Modal Assurance Criterion\" (MAC) para que um certo modo de vibrar seja encontrado, de modo que a freqüência de ressonância relacionada a esse modo seja otimizada. São apresentados exemplos para verificar a eficiência e a generalidade do método proposto, e também, um estudo sobre a influência dos parâmetros de otimização utilizadas no método. Por fim, são apresentados resultados que atendem a todos os requisitos de projeto, bem como seu pós-processamento, e análise no software comercial ANSYS®. / This work aims at the development of a method based on Topology Optimization to design a mechanical structure, called sonotrode, which is a device usually connected to a high power piezoelectric transducer (mechanical device capable of converting electric energy into mechanical displacement or vice-versa). A sonotrode transmits mechanical vibrations of a piezoelectric transducer, adjusting the amplitude and the distribution of these vibrations to fit the design needs of the transducer. Among applications of piezoelectric transducers using sonotrodes, we can cite navigation sonars, ultrasonic cleaning and melting, acoustic tomography, ultrasonic drilling, ultrasonic fabric cutting, etc. The design needs of the sonotrode differs for each application, ranging from obtaining maximum displacement in one single point of its structure, to obtaining uniform displacements on a whole face of the sonotrode. To improve the attainment of the optimum result, in this work \"Topology Optimization\" (TO) is applied to design the sonotrode. TO is a procedure to design the optimal layout of structures by distributing material within a fixed domain. The objective of the developed TO formulation is to find the best topology of the sonotrode that produces maximum and uniform displacements at one of its face. The TO method is implemented using the \"Sequential Linear Programming\" (SLP) as the optimization algorithm, and it is based on the \"Simple Isotropic Material with Penalization\" (SIMP) interpolation for material model formulation. It\'s also presented a study about the material model \"Rational Approximation of Material Properties\" (RAMP), in an attempt to reduce numerical instabilities like localized modes. \"Finite Element Method\" (FEM) is applied to model the sonotrode considering piezoelectric four-node axisymmetric elements. A node-based design variable implementation for continuum structural topology optimization is presented to minimize numerical instabilities such as \"checkerboard pattern\". The ressonance frequencies and modes are computed through Lanczos Method. A \"Modal Assurance Criterion\" (MAC) based formulation is used to track a certain mode, so that, the ressonance frequency related to this mode can be optimized. Examples are presented to verify the efficiency and the generality of the proposed method, and also, a study about the influence of the optimization parameters used in the method. Finally, results that meets all the design requirements are presented, as well as their post-processed topology, and the analysis in the commercial software ANSYS®.

Husmuttern AB är ett byggföretag som ligger i Eskilstuna. Dem bygger återvinningsbara modulhus och i samband med paketeringen tillverkar de även ett ”emballagecylinder” som säkrar produkterna vid leverans. Målet med detta examensarbete är att ge förbättringsförslag avseende effektivitet, säkerhet och ergonomi för den nya emballagecylindersmonteringsstationen. För att kunna uppfylla målet gjordes en litteraturstudie. Litteraturstudie gjordes för att kunna hitta olika metoder som sedan kunde tillämpas i en verkstad och göra checklistor för observation. Syftet med observationen var att beakta nuläget av emballagecylinderstationen för att kunna ge förbättringsförslag. Det gjordes även en FEMA-analys för att identifiera vilka säkerhetsrisker som finns i nuvarande stationen. Faktorer som identifierades var bland annat avsaknaden av en standard, utrymmet vid tillverkningen var bristfällig och det var enformigt utformade arbetsuppgifter. Projektet har resulterat i ett antal förbättringsförslag, exempelvis har lokalernas utnyttjandegrad effektiviserats för att ge anställda mer och säkrare arbetsutrymme. En standard för hur denna tillverkning ska genomföras har skapts med tydliga och korrekta ergonomiska anvisningar. / Husmuttern AB is a construction company located in Eskilstuna. They build recyclable modular houses. They also manufacture a "packaging cylinder" that secures the products upon delivery. This thesis aims to give suggestions for improvements in efficiency, safety, and ergonomics for the new packaging cylinder assembly station. To meet the goal, a literature study was conducted. A literature study was done to find different methods that could then be applied in a workshop and make checklists for observation. The purpose of the observation was to consider the current state of the packaging cylinder station to give suggestions for improvement. A FEMA analysis is performed to identify the safety risks at the current station. Factors that were identified included the lack of a standard, and the space during production was deficient and there were uniformly designed tasks. The project has resulted in several improvement proposals, such as the utilization rate of the premises has been streamlined to give employees more and safer workspace. A standard for how this production is to be carried out has been created with clear and correct ergonomic instructions.

Freeway merging VISSIM calibration techniques were developed for the analysis of ramp metering in Georgia. An analysis of VISSIM’s advanced merging and cooperative lane change settings was undertaken to determine their effects on merging behavior. Another analysis was performed to determine the effects of the safety reduction factor and the maximum deceleration for cooperative braking parameter on the simulated merging behavior. Results indicated that having both the advanced merging and cooperative lane change setting active produced the best results and that the safety reduction factor had more influence on the merging behavior than the maximum deceleration for cooperative braking parameter. Results also indicated that the on-ramp experienced unrealistic congestion when on-ramp traffic was unable to immediately find an acceptable gap when entering the acceleration lane. These vehicles would form a queue at the end of the acceleration lane and then be unable to merge into the freeway lane due to the speed differential between the freeway and the queued ramp traffic. An Incremental Desired Speed algorithm was developed to maintain an acceptable speed differential between the merging traffic and the freeway traffic. The Incremental Desired Speed algorithm resulted in a smoother merging behavior. Lastly, a ramp meter was introduced and an increase in both the freeway throughput and overall speeds was found. Implications of these findings on the future research is discussed.