Inactivating mutations in an SH2 domain-encoding gene in X-linked lymphoproliferative syndrome

X-linked lymphoproliferative syndrome (XLP) is an inherited immunodeficiency characterized by increased susceptibility to Epstein-Barr virus (EBV). In affected males, primary EBV infection leads to the uncontrolled proliferation of virus-containing B cells and reactive cytotoxic T cells, often culminating in the development of high-grade lymphoma. The XLP gene has been mapped to chromosome band Xq25 through linkage analysis and the discovery of patients harboring large constitutional genomic deletions. We describe here the presence of small deletions and intragenic mutations that specifically disrupt a gene named DSHP in 6 of 10 unrelated patients with XLP. This gene encodes a predicted protein of 128 amino acids composing a single SH2 domain with extensive homology to the SH2 domain of SHIP, an inositol polyphosphate 5-phosphatase that functions as a negative regulator of lymphocyte activation. DSHP is expressed in transformed T cell lines and is induced following in vitro activation of peripheral blood T lymphocytes. Expression of DSHP is restricted in vivo to lymphoid tissues, and RNA in situ hybridization demonstrates DSHP expression in activated T and B cell regions of reactive lymph nodes and in both T and B cell neoplasms. These observations confirm the identity of DSHP as the gene responsible for XLP, and suggest a role in the regulation of lymphocyte activation and proliferation. Induction of DSHP may sustain the immune response by interfering with SHIP-mediated inhibition of lymphocyte activation, while its inactivation in XLP patients results in a selective immunodeficiency to EBV.

Metais em águas e sedimentos da plataforma dos Açores

A presente tese tem por objetivo principal contribuir para o conhecimento da geoquímica sedimentar da zona oceânica da crista da Terceira e montanhas submarinas a sul (região entre 29-39ºN e 27-32ºW), integrando também a caraterização dos metais e nutrientes na coluna de água e propondo concentrações para servirem de referência nesta região do Atlântico Central. Para o efeito foram realizadas amostragens na coluna de água em sete locais e de sedimento em cinco locais, durante a campanha oceanográfica designada por EMEPC/AÇORES/G3/2007 a bordo do navio SV Kommandor Jack, no âmbito do projeto da Estrutura de Missão para a Extensão da Plataforma Continental (EMEPC). Os perfis de CTD da coluna de água na região estudada revelam a presença de massas de água distintas: a Western North Atlantic Central Water (WNACW), a Eastern North Atlantic Central Water tropical (ENACWt), a Eastern North Atlantic Central Water polar (ENACWp), a Mediterranean Overflow Water (MOW), a Deep Mediterranean Water (DMW) e a North Eastern Atlantic Deep Water (NEADW). Observou-se nos perfis de temperatura e salinidade, referentes aos primeiros 200 m da coluna de água, um gradiente meridional negativo entre as estações localizadas na crista da Terceira e as estações localizadas mais a sul. Observou-se nas águas superficiais valores de oxigénio dissolvido de 93% e de pH de 8,1, assim como que as concentrações dos nutrientes NOx, PO4 e SiO2 variam de acordo com a atividade biológica, tendo-se registado concentrações medianas mais baixas, respetivamente de 6,5, 0,23 e 1,3 mol L-1, que aumentam com a profundidade devido à ausência de produção primária (respetivamente 31, 1,4 e 22 mol L-1). As concentrações de NH4 e de SO4 não variam significativamente nas massas de água, sendo os valores medianos mínimos e máximos de 0,69 a 0,79 mol L-1 para o NH4 e de 30 a 32 mol L-1 para o SO4. São propostas concentrações de referência para as massas de água, para os elementos cobre, cádmio, chumbo e arsénio. Os perfis de sedimento analisados permitem distinguir os sedimentos na crista da Terceira (core A) dos restantes (cores B a E). A grande variabilidade textural encontrada no core A, que contrasta com os outros cores analisados, deve-se a importantes contribuições terrígenas, originadas pela erosão sub-aérea e pela atividade vulcânica das ilhas próximas. iv resumo (continuação) A análise mineralógica, efetuada à fração areia e à fração fina (< 63 μm), confirma que os sedimentos do core A derivam de rochas vulcânicas formadas maioritariamente por piroxenas, olivinas, anfíbolas, biotite, alterites e ainda calcite, plagióclase e magnetite, tendo-se identificado ao microscópio a glauconite e o vidro vulcânico. De acordo com a composição química destes minerais o core A apresenta valores mais elevados de Al, Fe, K, P, Mg, Si, Na, Zn, V, Cr e Mn relativamente aos cores B a E. Os cores B a E apresentam grandes quantidades de calcite (>80%) formada maioritariamente por foraminíferos e nanoplâncton calcário (cocolitóforos). A fração areia confirma a composição maioritariamente carbonatada com grande abundância de material biogénico formado por oozes de foraminíferos (planctónicos e bentónicos) com raras espículas de espongiários e restos de conchas. Os cores B a E apresentam valores muito mais elevados que o core A para os elementos Ca e Sr. Os resultados para o Al, Fe, K, P, Si, Na, As, Cu, Ni, Zn, V, Cr, Li, Pb, Cd e Co presentes nos locais B, C, D e E sugerem que estes cores são comparáveis aos sedimentos de fundo carbonatados. Propõe-se concentrações de referência para a região do Atlântico compreendida entre 29-39ºN e 27-32ºW considerando a primeira camada colhida em cada core. Para o core A as concentrações são normalizadas a 5% de Al e CaCO3, enquanto que para os cores B a E são normalizadas a 2% de Al e CaCO3. Assim as concentrações de referência para o core A são: As – 18 mg kg-1, Cr – 91 mg kg-1, Cu – 127 mg kg-1, Ni – 84 mg kg-1, Pb – 41 mg kg-1, Hg – 41 ng g-1 e Zn – 482 mg kg-1. Para os cores B a E as concentrações de referência são: As – 3 mg kg-1, Cr – 10 mg kg-1, Cu – 36 mg kg-1 Ni – 12 mg kg -1, Hg – 3 ng g-1 e Zn – 20 mg kg-1. Para os restantes metais as concentrações de referência para o core A são: Al – 9%, Si – 25%, Fe – 6%, Ca – 13%, K – 2%, Mg – 2%, Na – 3%, P – 0,4%, Sr – 900 mg kg-1, Li – 10 mg kg-1, Mn – 1200 mg kg-1, Ba – 700 mg kg-1 e V – 140 mg kg-1. Para os cores B a E as concentrações de referência são: Al – 0,9%, Si – 2%, Fe – 0,2%, Ca – 95%, K – 0,3%, Mg – 0,4%, Na – 0,3%, P – 0,04%, Sr – 2600 mg kg-1, Li – 5 mg kg-1, Mn – 240 mg kg-1, Ba – 345 mg kg-1, Co – 2 mg kg-1 e V – 6 mg kg-1. Os resultados da presente tese constituem um contributo para a caraterização geoquímica da região e podem servir de referência à monitorização futura do mar dos Açores e montes submarinos a sul.

Source localization with vector sensor array during the makai experiment

Vector sensors measure both the acoustic pressure and the three components of particle velocity. Because of this, a vector sensor array (VSA) has the advantage of being able to provide substantially higher directivity with a much smaller aperture than an array of traditional scalar (pressure only) hydrophones. Although several, most of them theoretic, works were published from early nineties, only in the last years due to improvements and availability of vector sensor technology, the interest on field experiments with VSA increased in the scientific community. During the Makai Experiment, that took place off the coast of Kauai I., Hawaii, in September 2005, real data were collected with a 4 element vertical VSA. These data will be discussed in the present paper. The acoustic signals were emitted from a near source (low frequency ship noise) and two high frequency controlled acoustic sources located within a range of 2km from the VSA. The advantages of the VSA over traditional scalar hydrophone arrays in source localization will be addressed using conventional beamforming.

The generation and propagation of internal waves in Nootka Sound

senior thesis written for Oceanography 445

Sonhos e desilusões com a República

O texto expressa uma reflexão sobre a obra Triste Fim de Policarmo Quaresma, escrita em 1915, por Lima Barreto, escritor realista, brasileiro. Busca identificar nas narrativas e ações do seu narrador, um homem comum, as revoltas, mas também as esperanças dos homens comuns no recém criado regime republicano. Enfoca ainda que, apesar dos episódios narrados, dos personagens serem construções ficcionais do autor, nos remetem a personagens, diálogos e espaços do Rio de Janeiro que evocam a historia de um regime ditatorial de Floriano Peixoto, no alvorecer da Republica. Nesse regime, mostra o autor, que a insegurança, a insatisfação e o medo tomaram conta da população do Rio de Janeiro no começo do século XX. E Policarpo Quaresma, o personagem narrador da obra, sofrera as injustiças e arbitrariedades da ditadura do Marechal Floriano Peixoto. Diante disso, revela sua dor e plena desolação com a Republica, forma de governo pelo qual lutara e que ajudara a criar. Por fim, o texto procura mostrar que embora a literatura seja tecida com adornos da ficção, ela traduz a sociedade e o tempo no qual ela foi produzida, além de mostrar que o positivismo sustentava a pratica política da Republica brasileira.

Sistema de visão para aterragem automática de UAV

Dissertação para obtenção do grau de Mestre em Engenharia Electrotécnica Ramo de Automação e Electrónica Industrial

Metodologia para otimização da manutenção

Trabalho Final de Mestrado para obtenção do grau de Mestre em Engenharia da Manutenção

Estudo da Viabilidade Técnico-Económica de umm Sistema de Cogeração para um Complexo de Piscinas Interiores

A presente dissertação centrou-se no estudo técnico-económico de dois cenários futuros para a continuação de fornecimento de energia térmica a um complexo de piscinas existente na região do vale do Tâmega. Neste momento a central de cogeração existente excedeu a sua licença de utilização e necessita de ser substituída. Os dois cenários em estudo são a compra de uma nova caldeira, a gás natural, para suprir as necessidades térmicas da caldeira existente a fuelóleo, ou o uso de um sistema de cogeração compacto que poderá estar disponível numa empresa do grupo. No primeiro cenário o investimento envolvido é cerca de 456 640 € sem proveitos de outra ordem para além dos requisitos térmicos, mas no segundo cenário os resultados são bem diferentes, mesmo que tenha de ser realizado o investimento de 1 000 000 € na instalação. Para este cenário foi efetuado um levantamento da legislação nacional no que toca à cogeração, recolheram-se dados do edifício como: horas de funcionamento, número de utentes, consumos de energia elétrica, térmica, água, temperatura da água das piscinas, temperatura do ar da nave, assim como as principais características da instalação de cogeração compacta. Com esta informação realizou-se o balanço de massa e energia e criou-se um modelo da nova instalação em software de modelação processual (Aspen Plus® da AspenTech). Os rendimentos térmico e elétrico obtidos da nova central de cogeração compacta foram, respetivamente, de 38,1% e 39,8%, com uma percentagem de perdas de 12,5% o que determinou um rendimento global de 78%. A avaliação da poupança de energia primária para esta instalação de cogeração compacta foi de 19,6 % o que permitiu concluir que é de elevada eficiência. O modelo criado permitiu compreender as necessidades energéticas, determinar alguns custos associados ao processo e simular o funcionamento da unidade com diferentes temperaturas de ar ambiente (cenários de verão e inverno com temperaturas médias de 20ºC e 5ºC). Os resultados revelaram uma diminuição de 1,14 €/h no custo da electricidade e um aumento do consumo de gás natural de 62,47 €/h durante o período mais frio no inverno devido ao aumento das perdas provocadas pela diminuição da temperatura exterior. Com esta nova unidade de cogeração compacta a poupança total anual pode ser, em média, de 267 780 € admitindo um valor para a manutenção de 97 698 €/ano. Se assim for, o projeto apresenta um retorno do investimento ao fim de 5 anos, com um VAL de 1 030 430 € e uma taxa interna de rentabilidade (TIR) de 14% (positiva, se se considerar a taxa de atualização do investimento de 3% para 15 anos de vida). Apesar do custo inicial ser elevado, os parâmetros económicos mostram que o projeto tem viabilidade económica e dará lucro durante cerca de 9 anos.

Comparación de los impactos ambientales y aspectos socioeconómicos de las cadenas de producción de anchoveta

Se presentan los primeros resultados del programa de investigación comparativo sobre las tres flotas pesqueras dedicadas a la extracción de anchoveta en el mar peruano (industrial de acero, industrial de madera y artesanal), así como sus cadenas de suministro hasta el abastecimiento del consumidor. El presente trabajo tiene por objetivo estudiar la sostenibilidad de las actividades involucradas en el suministro de proteínas, considerándose los impactos ambientales y los aspectos socio-económicos. Se realizó un esquema simple de un ecosistema pelágico de afloramiento y de los principales flujos de materia y energía, producto de la explotación humana. El esquema representa la situación peruana y muestra el alto nivel de antropización del sistema, debido al uso de energías fósiles, así como a la explotación y transformación tecnológica de recursos naturales terrestres (minerales, madera, etc.). Por otro lado, se muestra que la explotación del ecosistema marino peruano tiene repercusiones sobre el resto del planeta, debido a la exportación de harina y aceite de pescado destinados principalmente a actividades acuícolas. La flota anchovetera peruana se caracteriza por un amplio rango de tamaño de embarcaciones (de 2 a 600 t de capacidad de bodega); las de tamaño intermedio (30-100 t) son las más numerosas, pero las más grandes (>300 t) son las que acumulan el mayor poder de pesca. Los análisis sobre precios y distribución de la renta entre tripulantes y armadores muestran que, a pesar de que la mayor pesca de anchoveta es realizada por la flota industrial de acero, dedicada a la producción de harina y aceite de pescado y que tiene mayor eficiencia de captura por tripulante, la contribución de la pesca industrial de madera es significativa, pues genera mayor empleo por tonelada capturada y, posiblemente, no ocasiona mayor uso de energía. La pesca artesanal de anchoveta es la menos eficiente energéticamente y por tripulante, pero genera mucho más empleo por tonelada capturada; esta pesca representa menos del 3% de la producción total, del cual sólo una fracción va al consumo humano directo (CHD). Desde el año 2000, los precios de harina y aceite de pescado en los mercados internacionales se han incrementado, debido al aumento de la demanda asiática y al precio del combustible. Se debe estudiar en qué medida este aumento desfavorece el consumo interno de estos productos, así como el uso de anchoveta para CHD. Este análisis deberá ser validado y complementado con información de impacto ambiental; y podrían contribuir a la toma de decisión participativa, para un balance óptimo entre los tres segmentos de la flota y las cadenas de producción asociadas.

The influence of investigator disturbance on aggressive behaviour and breeding success of ring-billed gulls (Larus delawarensis) /

Increased losses of eggs and chicks resulting from human intrusion (investigator or other) into seabird colonies has been well documented. In 1990/91, I studied the effects of investigator disturbance on aggressive behaviour and breeding success of individual pairs of ring-billed gulls nesting at two colonies near Port Colborne, Ontario. The insular colony was on an artificial breakwall, associated with the Welland Ship Canal, approximately 1 km off the north shore of Lake Erie. The mainland colony was adjacent to the canal approximately 1 km east of the breakwall. The frequencies of adult threat and assault behaviours, chick movement and adult attacks on chicks were recorded by continuous scan sampling 30 min prior to, 30 min during and 60 (2 X 30) min after investigator disturbance. The frequency of threat and assault behaviours increased during the period of investigator activity in the colony while the duration of wingpulls and beakpulls decreased. Significantly more chicks ran ("runners") from their natal territories during disturbances and "runners" were more frequently attacked than "territorial" chicks. No chicks were fatally attacked during disturbance and "runners" returned to their natal territories quickly after disturbance. Breeding success was determined for pairs nesting in study plots subjected to two levels of disturbance (normal and moderate). The disturbance level of each plot differed in visitation frequency and activities performed on each visit. Investigator disturbance had no effect on the hatching success or fledging success (taken as 21 days of age) of ring-billed gull study pairs at either colony.

Water quality and fish populations of the Welland River, Ontario /

The water quality and fish populations of the Welland River were observed to decline with distance downstream. This coincided with increased agricultural , domestic and industrial waste loadings. The river upstream of the City of Welland received considerable loadings from agricultural sources. Centrarchids, sciaenids, ictalurids, cyprinids and esocids characterized this upper section of the river. Most of these species were tolerant of low dissolved oxygen concentrations and the high turbidity which prevailed there . The river near Port Robinson receives many industrial and domestic wastes as evidenced by the water quality data. The fish in this section were less abundant and the observed population was comprised almost solely of cyprinids. Further downstream, near Montrose, the Welland River received shock loads of chemical wastes that exceeded a specific conductance of ISiOOO ;umhos/cm. Few fish were captured at this site and those that were captured were considered to be transients. A review of the literature revealed that none of the common indices of water quality in use today could adequately predict the observed distributions. In addition to the above, the long-term trend (l3 yrs) of water quality of the lower Welland River revealed a gradual improvement. The major factor thought to be responsible for this improvement was the operation of the Welland Sewage Treatment Plant. The construction of the New Welland Ship Canal coincided with large fluctuations of the total solids and other parameters downstream. These conditions prevailed for a maximum of three years (1972- 1975)' Furthermore, spawning times and temperatures, geographic distributions, length-weight regressions and many other descriptive aspects of the ecology of some 26 species/ taxa of fish were obtained. Several of these species are rare or new to southern Ontario.

Acquisition and transfer of experiential learning from rock climbing to the corporate workplace

There were three purposes to this study. The first purpose was to determine how learning can be influenced by various factors i~ the rock climbing experience. The second purpose was to examine what people can learn from the rock climbing experience. The third purpose was to investigate whether that learning can transfer from the rock climbing experience to the subjects' real life in the workplace. Ninety employees from a financial corporation in the Niagara Region volunteered for this study. All subjects were surveyed throughout a one-day treatment. Ten were purposefully selected one month later for interviews. Ten themes emerged from the subjects in terms of what was learned. Inspiration, motivation, and determination, preparation, goals and limitations, perceptions and expectations, confidence and risk taking, trust and support, teamwork, feedback and encouragement, learning from failure, and finally, skills and flow. All participants were able to transfer what was learned back to the workplace. The results of this study suggested that subjects' learning was influenced by their ability to: take risks in a safe environment, fail without penalty, support each other, plan without time constraints, and enjoy the company of fellow workers that they wouldn't normally associate with. Future directions for research should include different types of treatments such as white water rafting, sky diving, tall ship sailing, or caving.

Scott Misener Steamships Co. Ltd. Records, 1965, 1967, 1972-1977, 1987, n.d.

Ontario Editorial Bureau (O.E.B.)

Hugh Alexander Papers, 1811-1816 [photocopy]

Hugh Alexander, b. 1780 arrived in Niagara shortly after his birth. He attended school and later apprenticed as a clerk. In 1797 he was granted 200 acres of land in Bertie township and became a merchant and trader in Fort Erie. He was the owner of a sailing vessel, the Chippawa, which he used to transport goods in the area. The ship was lost and/or confiscated as a result of War of 1812 skirmishes on Lake Erie. By 1812 Hugh Alexander was in business together with his brother Ephraim. The Alexander’s storehouse, store and house were burned by the British military when they abandoned Fort Erie ahead of the invading American military in late May 1813. At the time of the burning, Hugh Alexander was engaged as a Lieutenant with the 3rd Lincoln Militia. Prior to this Hugh Alexander had established a second mercantile in Stamford, opposite the green. Misfortune was to strike at this location as well when the British military abandoned the whole of the Niagara area to the invading American forces and the Stamford location was looted. After the end of the hostilities Alexander went on to rebuild his storehouse in Fort Erie and to re-establish his store in Stamford. Hugh Alexander died on November 2, 1817 and is buried in the Stamford Presbyterian Cemetery. Source: George A. Seibel, The Niagara Portage Road: 200 Years 1790-1990. Niagara Falls: City of Niagara Falls, 1990, p. 259-262.

The Welland Canals Foundation, Honourable William Hamilton Merritt and the St. Catharines Historical Society and Museum, 1971-1990, n.d.

‘The Father of Canadian Transportation’ is a term commonly associated with William Hamilton Merritt. Although he is most known for being one of the driving forces behind the building of the first Welland Canal, he was many things throughout his life; a soldier, merchant, promoter, entrepreneur and politician to name a few. Born on July 3, 1793 at Bedford, Westchester County, N.Y. to Thomas Merritt and Mary Hamilton, Merritt’s family relocated to Canada shortly after in 1796. The move came after Merritt’s father petitioned John Graves Simcoe for land in Upper Canada after serving under him in the Queen’s Rangers during the American Revolution. The family quickly settled into their life at Twelve Mile Creek in St. Catharines. Merritt’s father became sheriff of Lincoln County in 1803 while Merritt began his education in mathematics and surveying. After some brief travel and further education Merritt returned to Lincoln County, in 1809 to help farm his father’s land and open a general store. While a farmer and merchant, Merritt turned his attention to military endeavours. A short time after being commissioned as a Lieutenant in the Lincoln militia, the War of 1812 broke out. Fulfilling his duty, Merritt fought in the Battle of Queenston Heights in October of 1812, and numerous small battles until the Battle of Lundy’s Lane in July 1814. It was here that Merritt was captured and held in Cheshire, Massachusetts until the war ended. Arriving back in the St. Catharines area upon his release, Merritt returned to being a merchant, as well as becoming a surveyor and mill owner. Some historians hypothesize that the need to draw water to his mill was how the idea of the Welland Canals was born. Beginning with a plan to connect the Welland River with the Twelve mile creek quickly developed into a connection between the Lakes Erie and Ontario. Its main purpose was to improve the St. Lawrence transportation system and provide a convenient way to transport goods without having to go through the Niagara Falls portage. The plan was set in motion in 1818, but most living in Queenston and Niagara were not happy with it as it would drive business away from them. Along with the opposition came financial and political restraints. Despite these factors Merritt pushed on and the Welland Canal Company was chartered by the Upper Canadian Assembly on January 19, 1824. The first sod was turned on November 30, 1824 almost a year after the initial chartering. Many difficulties arose during the building of the canal including financial, physical, and geographic restrictions. Despite the difficulties two schooners passed through the canal on November 30, 1829. Throughout the next four years continual work was done on the canal as it expended and was modified to better accommodate large ships. After his canal was underway Merritt took a more active role in the political arena, where he served in various positions throughout Upper Canada. In 1851, Merritt withdrew from the Executive Council for numerous reasons, one of which being that pubic interest had diverted from the canals to railways. Merritt tried his hand at other public works outside transportation and trade. He looked into building a lunatic asylum, worked on behalf of War of 1812 veterans, aided in building Brock’s monument, established schools, aided refugee slaves from the U.S. and tried to establish a National Archives among many other feats. He was described by some as having “policy too liberal – conceptions too vast – views too comprehensive to be comprehensible by all”, but he still made a great difference in the society in which he lived. After his great contributions, Merritt died aboard a ship in the Cornwall canal on July 5, 1862. Dictionary of Canadian Biography Online http://www.biographi.ca/EN/ShowBio.asp?BioId=38719 retrieved October 2006 Today numerous groups carry on the legacy of Merritt and the canals both in the past and present. One such group is the Welland Canals Foundation. They describe themselves as: “. . . a volunteer organization which strives to promote the importance of the present and past Welland Canals, and to preserve their history and heritage. The Foundation began in 1980 and carries on events like William Hamilton Merritt Day. The group has strongly supported the Welland Canals Parkway initiative and numerous other activities”. The Welland Canals Foundation does not work alone. They have help from other local groups such as the St. Catharines Historical Society. The Society’s main objective is to increase knowledge and appreciation of the historical aspects of St. Catharines and vicinity, such as the Welland Canals. http://www.niagara.com/~dmdorey/hssc/dec2000.html - retrieved Oct. 2006 http://www.niagara.com/~dmdorey/hssc/feb2000.html - retrieved Oct. 2006