Performance requirements of short-distance digital communication links have increased considerably with the escalating demand for high speed and high density data links. The high aggregate bandwidth and channel density achievable by free-space optical interconnects (FSOIs) make them ideal replacement for electrical interconnection schemes. Optical interconnects potentially have low power consumption, and can facilitate the development of radically novel designs for VLSI architectures including heterogeneous multiprocessor systems, and highly parallel computing systems. Recent developments in the integration of Vertical-Cavity Surface-Emitting Laser (VCSEL) arrays and photodetector arrays with CMOS electronic circuitry have increased the practical potential of optical interconnects. However, VCSELs tend to operate in several transverse modes simultaneously, which will degrade the performance of FSOIs. Experimental investigation was performed to evaluate the operation characteristics and the intensity noise in VCSELs. The measurement results were later combined with optical simulations to analyse the effect of optical crosstalk in free-space optical interconnects. The VCSEL characterization included light-current-voltage relationships, relative intensity noise, modal spectral composition and modal beam profiles. The optical system simulation software (Code V) was used to simulate optical crosstalks in the FSOI system. Experimentally measured spectrally-resolved near-field images of VCSEL higher order modes were used as extended sources in the proposed simulation model. The simulation was performed using a combination of exact ray-tracing and the beam propagation method. A new type of crosstalk referred to as the stray-light crosstalk (SLC) was introduced. This type of crosstalk is caused by the overfill of the transmitter microlens by the VCSEL beam. It was discovered that part of the signal was imaged by the adjacent microlens to another channel, possibly far from the intended one. The simulation showed that the SLC is strongly dependent on the fill factor of the microlens, array pitch, and the channel density of the system. When comparing the diffraction-caused crosstalk (DCC) to SLC, an increase in the interconnection distance has little influence on the SLC. A simple behavioural model was developed which accurately approximates the crosstalk noise for a range of optical sources and interconnect configurations. The effect of transmitter and receiver array configurations on the performance of FSOIs was investigated. Our results demonstrate the importance of SLC in both square and hexagonal configuration. By changing the array lattice geometry from square to a hexagonal, we obtained an overall optical signal-to-noise ratio (SNR) improvement of 3 dB. The optical SNR is optimal for the hexagonal channel arrangement regardless of the transverse mode structure of the VCSEL beam was shown. Furthermore, the VCSEL drive current required for the best performance of the FSOI system was determined. The optimal focal length of the transmitter microlens array which maximises the SNR by minimising the combined effects of DCC and SLC was determined. Our results show that shorter focal length needs to be used for higher order modes to obtain optimal SNR in an FSOI system.

The har1-1 mutant of Lotus japonicus line Gifu is characterised by increased nodulation and significantly inhibited root growth in the presence of its microsymbiont Mesorhizoboium loti (for example strain NZP2235). A sexual cross between the mutant and another L. japonicus genotype Funakura (with wild-type root and nodule morphology) demonstrated Mendelian recessive segregation of both phenotypes (for root and nodule) in 242 F2 individuals. No separation of phenotypes was observed, suggesting a single mutation with pleiotropic effects. Reciprocal grafting showed that the har1-1 controlled phenotype is governed by the shoot. Using a skeletal genetic map of arbitrary molecular markers produced from a Gifu x Funakura cross, the har1-1 locus was positioned between two markers at about 7 and 13 cM distance. Single nucleotide polymorphisms (SNPs) and transgene sequences were detected by allele-specific PCR in DNA isolated from small (1 mg mass) individual seeds and half-cotyledon of the model legume Lotus japonicus, allowing fast determination of a seedling’s genomic status. This permitted a shortening of the breeding cycle for multi-trait seed lines. Fast neutron mutagenesis of Lotus japonicus wild-type genotype Gifu resulted in the first time isolation of a stable mutant (FNN5-2) unable to form nitrogen-fixing nodules in symbiosis with Mesorhizobium loti, though being infected by mycorrhizal fungi. The mutation behaves as a loss-of-function recessive, and has no other apparent phenotypic effects. Molecular characterization indicates a partial loss of the LjNFR1 LysM type receptor kinase gene. Additionally part of the LjNIN gene (encoding a putative transcription factor needed for nodulation) is also missing. Transcript levels for both genes are severely reduced. As LjNIN and LjNFR1 are in the same chromosomal region we tested whether this terminal portion is lacking. PCR analysis confirms that genes within the relevant interval (such as LjPAL1 (encoding phenylalanine ammonia lyase) and LjEIL2 (encoding an ethylene insensitive-like response regulator)) are present, suggesting that the mutational event induced by the fast neutrons was either a double hit coincidently involving two nodulation-related genes, a major genome rearrangement, or a major segmental inversion. To develop an integrated nodule developmental model based on gene interactions in autoregulation, nodulation and plant hormone response deficient lines, HE double mutants have been built using the har1-1 mutant (hypernodulation and aberrant root) and the ethylene insensitive transgenic line Etr1-1. The homozygous loss-of-function mutant har1-1 has increased nodulation and decreased root growth. Ethylene insensitivity mediated by the transgene 35S::AtETR1-1 restores the normal root growth. The HE double mutants were confirmed by triple response test and allele- or gene-specific PCR. The current results in this study indicate that a) HE double mutants shown the same nodulation pattern as har1-1 and normal root formation as Etr1-1, suggesting that nodule and root control diverge at some stage with root control being ethylene-mediated and the Har1 gene, the orthologue of GmNARK is involved in nodulation. b) Grafting demonstrated that the shoot is the source of ethylene suppression of the har1-1 induced inhibition of root growth. c) The mutated Etr1-1 gene was able to replace AVG in BAP root inhibition; d) IPT-dependent cytokinin overproduction led to aberrant root architecture in har1-1; e) Crosstalk between ethylene and cytokinin in HE double mutant by qRT-PCR.

Performance requirements of short-distance digital communication links have increased considerably with the escalating demand for high speed and high density data links. The high aggregate bandwidth and channel density achievable by free-space optical interconnects (FSOIs) make them ideal replacement for electrical interconnection schemes. Optical interconnects potentially have low power consumption, and can facilitate the development of radically novel designs for VLSI architectures including heterogeneous multiprocessor systems, and highly parallel computing systems. Recent developments in the integration of Vertical-Cavity Surface-Emitting Laser (VCSEL) arrays and photodetector arrays with CMOS electronic circuitry have increased the practical potential of optical interconnects. However, VCSELs tend to operate in several transverse modes simultaneously, which will degrade the performance of FSOIs. Experimental investigation was performed to evaluate the operation characteristics and the intensity noise in VCSELs. The measurement results were later combined with optical simulations to analyse the effect of optical crosstalk in free-space optical interconnects. The VCSEL characterization included light-current-voltage relationships, relative intensity noise, modal spectral composition and modal beam profiles. The optical system simulation software (Code V) was used to simulate optical crosstalks in the FSOI system. Experimentally measured spectrally-resolved near-field images of VCSEL higher order modes were used as extended sources in the proposed simulation model. The simulation was performed using a combination of exact ray-tracing and the beam propagation method. A new type of crosstalk referred to as the stray-light crosstalk (SLC) was introduced. This type of crosstalk is caused by the overfill of the transmitter microlens by the VCSEL beam. It was discovered that part of the signal was imaged by the adjacent microlens to another channel, possibly far from the intended one. The simulation showed that the SLC is strongly dependent on the fill factor of the microlens, array pitch, and the channel density of the system. When comparing the diffraction-caused crosstalk (DCC) to SLC, an increase in the interconnection distance has little influence on the SLC. A simple behavioural model was developed which accurately approximates the crosstalk noise for a range of optical sources and interconnect configurations. The effect of transmitter and receiver array configurations on the performance of FSOIs was investigated. Our results demonstrate the importance of SLC in both square and hexagonal configuration. By changing the array lattice geometry from square to a hexagonal, we obtained an overall optical signal-to-noise ratio (SNR) improvement of 3 dB. The optical SNR is optimal for the hexagonal channel arrangement regardless of the transverse mode structure of the VCSEL beam was shown. Furthermore, the VCSEL drive current required for the best performance of the FSOI system was determined. The optimal focal length of the transmitter microlens array which maximises the SNR by minimising the combined effects of DCC and SLC was determined. Our results show that shorter focal length needs to be used for higher order modes to obtain optimal SNR in an FSOI system.

Cadherin-based cell-cell contacts are prominent sites for phosphotyrosine signalling, being enriched in tyrosine-phosphorylated proteins, tyrosine kinases and phosphatases. The functional interplay between cadherin adhesion and tyrosine kinase signalling, however, is complex and incompletely understood. In my thesis I have tested the hypothesis that c-Src contributes positively to cadherin biology by functioning as part of an adhesion activated cell-signalling pathway. I found that c-Src is active at both established and reforming cell-cell contacts, and c-Src can be activated by homophilic ligation of the adhesion receptor. However, c-Src has a biphasic impact on cadherin function, exerting a positive supportive role at lower signal strengths, but inhibiting function at high signal strengths. Inhibiting c-Src under circumstances when it is activated by cadherin adhesion decreased several measures of cadherin function. This suggests that the cadherin-activated c-Src signalling pathway serves positively to support cadherin function, while quantitative changes in signal strength may result in qualitative differences in functional outcome. Finally, my data implicated PI3-kinase signalling and cortactin as potential targets for cadherin-activated c-Src signalling. By inhibiting protein tyrosine phosphatases with pervanadate, I found that tyrosine phosphatase activity and not just protein binding was required to stimulate Src activity in response to cadherin ligation. I identified the tyrosine phosphatase RPTPα as a possible regulator of cadherin-activated Src signalling. RPTPα localises to cell-cell adhesions and it is found in a complex with E-cadherin and c-Src. Furthermore, knockdown of RPTPα disrupted the integrity of cadherin-based contacts and the activity of Src at these cell-cell contacts. This suggests that in response to cadherin-homophilic ligation PTP activity is required to stimulate Src signalling. Finally, I identified a novel pathway by which aberrant growth factor signalling could be downregulating cadherin function and promoting the invasion of epithelial cells. Stimulating cells with high levels of EGF revealed that aberrant epidermal growth factor signalling could disrupt cadherin-activated cell signalling. The integrity of cadherin-based contacts and the activity of Src at the cell-cell contacts were both disrupted in the presence of high levels of EGF. Analysis of E-cadherin and RPTPα immunoprecipitates suggested that activation of cadherin-bound EGFR might disrupt Src activation by displacing E-cadherin-RPTPα binding. Finally, analysing the subcellular distribution of these proteins revealed that, in response to high levels of EGF, E-cadherin, β-catenin, EGFR and pEGFR are internalised together in phospho-cortactin-rich endosomal-like structures. Therefore I propose that E-cadherin adhesion activates a cell-signalling pathway involving c-Src that functions to dynamically regulate the actin cytoskeleton and to maintain the adhesive strength of cell-cell adhesions. Perturbation of cadherin-activated Src signalling downregulates cadherin function and promotes the disassembly of cell-cell adhesive contacts. The concept of a cadherin-activated Src signalling pathway provides a new way to think about cadherin biology. Instead of merely functioning as passive glue holding two cells together, E-cadherin functions as an adhesion-activated signalling receptor. Dysregulation of E-cadherin-activated Src signalling and downregulation of cell-cell adhesions could be a mechanism promoting the invasion and metastasis of epithelial tumours.

Thesis (M.S.)--Rochester Institute of Technology, 2009. / Typescript. Includes bibliographical references (p. 116-119).

Thesis (Ph.D.) - Carleton University, 2005. / Includes bibliographical references (p. 170-180). Also available in electronic format on the Internet.

Com a redução das dimensões dos dispositivos nas tecnologias sub-micrônicas foi possível um grande aumento no número de IP cores integrados em um mesmo chip e consequentemente novas arquiteturas de comunicação são usadas bucando atingir os requisitos de desempenho e potência. As redes intra-chip (Networks-on-Chip) foram propostas como uma plataforma alternativa de comunicação capaz de prover interconexões e comunicação entre os cores de um mesmo chip, tratando questões como desempenho, consumo de energia e reusabilidade para grandes sistemas integrados. Por outro lado, a mesma evolução tecnológica dos processos nanométricos reduziu drasticamente a confiabilidade de circuitos integrados, tornando dispositivos e interconexões mais sensíveis a novos tipos de falhas. Erros podem ser gerados por variações no processo de fabricação ou mesmo pela susceptibilidade do projeto, quando este opera em um ambiente hostil. Na comunicação de NoCs as duas principais fontes de erros são falhas de crosstalk e soft errors. No passado, se assumia que interconexões não poderiam ser afetadas por soft errors, por não possuirem circuitos seqüenciais. Porém, quando NoCs são usadas, buffers e circuitos seqüenciais estão presentes nos roteadores e, consequentemente, podem ocorrer soft errors entre a fonte e o destino da comunicação, provocando erros. Técnicas de tolerância a falhas, que tem sido aplicadas em circuitos em geral, podem ser usadas para proteger roteadores contra bit-flips. Neste cenário, este trabalho inicia com a avaliação dos efeitos de soft errors e falhas de crosstalk em uma arquitetura de NoC, através de simulação de injeção de falhas, analisando detalhadamente o impacto de tais falhas no roteador. Os resultados mostram que os efeitos dessas falhas na comunicação do SoC podem ser desastrosos, levando a perda de pacotes e travamento ou indisponibilidade do sistema. Então é proposta e avaliada a aplicação de um conjunto de técnicas de tolerância a falhas em roteadores, possibilitando diminuir os soft errors e falhas de crosstalk no nível de hardware. Estas técnicas propostas foram baseadas em códigos de correção de erros e redundância de hardware. Resultados experimentais mostram que estas técnicas podem obter zero erros com 50% a menos de overhead de área, quando comparadas com a duplicação simples. Entretanto, algumas dessas técnicas têm um grande consumo de potência, pois toda essas técnicas são baseadas na adição de hardware redundante. Considerando que as técnicas de proteção baseadas em software também impõe um considerável overhead na comunicação devido à retransmissão, é proposto o uso de técnicas mistas de hardware e software, que podem oferecer um nível de proteção satisfatório, baseado na análise do ambiente onde o sistema irá operar (soft error rate), fatores relativos ao projeto e fabricação (variações de atraso em interconexões, pontos susceptíveis a crosstalk), a probabilidade de uma falha gerar um erro em um roteador, a carga de comunicação e os limites de potência e energia suportados. / As the technology scales down into deep sub-micron domain, more IP cores are integrated in the same die and new communication architectures are used to meet performance and power constraints. Networks-on-Chip have been proposed as an alternative communication platform capable of providing interconnections and communication among onchip cores, handling performance, energy consumption and reusability issues for large integrated systems. However, the same advances to nanometric technologies have significantly reduced reliability in mass-produced integrated circuits, increasing the sensitivity of devices and interconnects to new types of failures. Variations at the fabrication process or even the susceptibility of a design under a hostile environment might generate errors. In NoC communications the two major sources of errors are crosstalk faults and soft errors. In the past, it was assumed that connections cannot be affected by soft errors because there was no sequential circuit involved. However, when NoCs are used, buffers and sequential circuits are present in the routers, consequently, soft errors can occur between the communication source and destination provoking errors. Fault tolerant techniques that once have been applied in integrated circuits in general can be used to protect routers against bit-flips. In this scenario, this work starts evaluating the effects of soft errors and crosstalk faults in a NoC architecture by performing fault injection simulations, where it has been accurate analyzed the impact of such faults over the switch service. The results show that the effect of those faults in the SoC communication can be disastrous, leading to loss of packets and system crash or unavailability. Then it proposes and evaluates a set of fault tolerant techniques applied at routers able to mitigate soft errors and crosstalk faults at the hardware level. Such proposed techniques were based on error correcting codes and hardware redundancy. Experimental results show that using the proposed techniques one can obtain zero errors with up to 50% of savings in the area overhead when compared to simple duplication. However some of these techniques are very power consuming because all the tolerance is based on adding redundant hardware. Considering that softwarebased mitigation techniques also impose a considerable communication overhead due to retransmission, we then propose the use of mixed hardware-software techniques, that can develop a suitable protection scheme driven by the analysis of the environment that the system will operate in (soft error rate), the design and fabrication factors (delay variations in interconnects, crosstalk enabling points), the probability of a fault generating an error in the router, the communication load and the allowed power or energy budget.

This thesis provides analytical and forensic tools for data cabling, with particular focus on Ethernet cabling to assist designers and those involved in deployments in analyzing cable performance and the reasons behind the actual performance obtained. The need for higher bandwidth to accommodate increasing demand for multimedia services and data centers network infrastructure led to the formation of IEEE P802.3bq to create standards for 40GBASE-T over twisted pair cables. The 40GBASE-T is expected to offer bandwidth of up to 2000MHz over a maximum channel length of 30m. The research investigated means of predicting key performance parameters in Ethernet cabling standardization using the 40GBASE-T as an example. The performance parameters prediction method provided is equally applicable to ongoing and future high data rate Ethernet cabling standardization such as the 2.5/5GBASE-T and 50/100GBASE-T. Another problem in the Ethernet networking world is the availability of counterfeit and non-standards compliant twisted pair cables in the market. The significant amount of communications cables in the market containing copper clad aluminum cable or other non-standards compliant conductors disguised as Category 6 cables can pose serious problems to companies’ networks, the contractors or the installers. This is in view of the growing demand for internet of things (IOT) services that makes it imperative to have a reliable Ethernet driven communication network to support the required infrastructure. This thesis therefore, provides techniques that can be used to evaluate cables key performance parameters using the Feature Selective Validation method and the Kolmogorov-Smirnov (KS) test. The technique can help engineers avoid subjective judgement and make objective decisions in the selection of cables. The research provided a technique that can be used to reverse engineer impedance profile from the return loss measurement of Ethernet cables using genetic algorithms. The method can be applied in situations where time domain tests are inaccessible or only simple (magnitude) tests in the frequency domain are available and there is the need for impedance profiles of cables to evaluate their performance or physical integrity before or after installation. The method can also be useful where only simple (magnitude) tests are the only historical data available for the cables and facilities for time domain reflectometry measurements are inaccessible. This research also presented a method of evaluating and predicting NEXT in unshielded twisted pair (UTP) using Category 6 cables as an example. The results obtained from the evaluation were used to provide crosstalk parameters for fast NEXT prediction in Category 6 (UTP) cables. The research used the measured NEXT of three Category 6 (UTP) cables from different manufacturers for evaluation and validation. The evaluation and modeling method can thus be useful to engineers investigating NEXT in the design of data communication systems.

Idiopathic pulmonary fibrosis (IPF) is a disease of unknown aetiology, characterised by the progressive and irreversible scarring of parenchymal lung tissue that leads to respiratory failure and death. The disease is understood to be driven by an impaired and aberrant wound healing response, with an inappropriate reactivation of developmental signalling. The greatest risk factor for the disease is age, which is a process intimately associated with an increase in the burden of senescent cells. Such cells acquire a unique secretory phenotype and are known to have a significant impact on their local micro-environment. It was hypothesised that an alteration in epithelial-mesenchymal secretory communication, due to senescent-like changes in the fibroblast phenotype, may detrimentally contribute to lung homeostasis. An in vitro model of the lung airway was established in which primary human lung fibroblasts (HLFs) were co-cultured with human bronchial epithelial cells (HBECs). HBECs were cultured on a semi-permeable, transwell insert and co-cultured with either normal (NHLF), fibrotic (FHLF) or senescent fibroblasts. Over 72 hrs of co-culture, wound healing was assessed, via an epithelial scratch assay, and epithelial regeneration was measured, via trans-epithelial electrical resistance. Co-culture with NHLFs improves epithelial regeneration, however, FHLFs and senescent cells in co-culture show a diminished ability to promote epithelial regeneration and wound repair. The secretory repertoire of these cells contains elevated levels of IL-6, CXCL8, CXCL1 and GCSF (when assessed at both an RNA and protein level), factors strongly associated with the senescent phenotype. Targeting this secretome via treatment with the JAK 1/2 inhibitor Ruxolitinib attenuates these impairments and may point towards a new therapeutic strategy for the treatment of IPF.

Com a redução das dimensões dos dispositivos nas tecnologias sub-micrônicas foi possível um grande aumento no número de IP cores integrados em um mesmo chip e consequentemente novas arquiteturas de comunicação são usadas bucando atingir os requisitos de desempenho e potência. As redes intra-chip (Networks-on-Chip) foram propostas como uma plataforma alternativa de comunicação capaz de prover interconexões e comunicação entre os cores de um mesmo chip, tratando questões como desempenho, consumo de energia e reusabilidade para grandes sistemas integrados. Por outro lado, a mesma evolução tecnológica dos processos nanométricos reduziu drasticamente a confiabilidade de circuitos integrados, tornando dispositivos e interconexões mais sensíveis a novos tipos de falhas. Erros podem ser gerados por variações no processo de fabricação ou mesmo pela susceptibilidade do projeto, quando este opera em um ambiente hostil. Na comunicação de NoCs as duas principais fontes de erros são falhas de crosstalk e soft errors. No passado, se assumia que interconexões não poderiam ser afetadas por soft errors, por não possuirem circuitos seqüenciais. Porém, quando NoCs são usadas, buffers e circuitos seqüenciais estão presentes nos roteadores e, consequentemente, podem ocorrer soft errors entre a fonte e o destino da comunicação, provocando erros. Técnicas de tolerância a falhas, que tem sido aplicadas em circuitos em geral, podem ser usadas para proteger roteadores contra bit-flips. Neste cenário, este trabalho inicia com a avaliação dos efeitos de soft errors e falhas de crosstalk em uma arquitetura de NoC, através de simulação de injeção de falhas, analisando detalhadamente o impacto de tais falhas no roteador. Os resultados mostram que os efeitos dessas falhas na comunicação do SoC podem ser desastrosos, levando a perda de pacotes e travamento ou indisponibilidade do sistema. Então é proposta e avaliada a aplicação de um conjunto de técnicas de tolerância a falhas em roteadores, possibilitando diminuir os soft errors e falhas de crosstalk no nível de hardware. Estas técnicas propostas foram baseadas em códigos de correção de erros e redundância de hardware. Resultados experimentais mostram que estas técnicas podem obter zero erros com 50% a menos de overhead de área, quando comparadas com a duplicação simples. Entretanto, algumas dessas técnicas têm um grande consumo de potência, pois toda essas técnicas são baseadas na adição de hardware redundante. Considerando que as técnicas de proteção baseadas em software também impõe um considerável overhead na comunicação devido à retransmissão, é proposto o uso de técnicas mistas de hardware e software, que podem oferecer um nível de proteção satisfatório, baseado na análise do ambiente onde o sistema irá operar (soft error rate), fatores relativos ao projeto e fabricação (variações de atraso em interconexões, pontos susceptíveis a crosstalk), a probabilidade de uma falha gerar um erro em um roteador, a carga de comunicação e os limites de potência e energia suportados. / As the technology scales down into deep sub-micron domain, more IP cores are integrated in the same die and new communication architectures are used to meet performance and power constraints. Networks-on-Chip have been proposed as an alternative communication platform capable of providing interconnections and communication among onchip cores, handling performance, energy consumption and reusability issues for large integrated systems. However, the same advances to nanometric technologies have significantly reduced reliability in mass-produced integrated circuits, increasing the sensitivity of devices and interconnects to new types of failures. Variations at the fabrication process or even the susceptibility of a design under a hostile environment might generate errors. In NoC communications the two major sources of errors are crosstalk faults and soft errors. In the past, it was assumed that connections cannot be affected by soft errors because there was no sequential circuit involved. However, when NoCs are used, buffers and sequential circuits are present in the routers, consequently, soft errors can occur between the communication source and destination provoking errors. Fault tolerant techniques that once have been applied in integrated circuits in general can be used to protect routers against bit-flips. In this scenario, this work starts evaluating the effects of soft errors and crosstalk faults in a NoC architecture by performing fault injection simulations, where it has been accurate analyzed the impact of such faults over the switch service. The results show that the effect of those faults in the SoC communication can be disastrous, leading to loss of packets and system crash or unavailability. Then it proposes and evaluates a set of fault tolerant techniques applied at routers able to mitigate soft errors and crosstalk faults at the hardware level. Such proposed techniques were based on error correcting codes and hardware redundancy. Experimental results show that using the proposed techniques one can obtain zero errors with up to 50% of savings in the area overhead when compared to simple duplication. However some of these techniques are very power consuming because all the tolerance is based on adding redundant hardware. Considering that softwarebased mitigation techniques also impose a considerable communication overhead due to retransmission, we then propose the use of mixed hardware-software techniques, that can develop a suitable protection scheme driven by the analysis of the environment that the system will operate in (soft error rate), the design and fabrication factors (delay variations in interconnects, crosstalk enabling points), the probability of a fault generating an error in the router, the communication load and the allowed power or energy budget.