Urocortin – From Parkinson’s disease to the skeleton

Urocortin (Ucn 1), a 40 amino acid long peptide related to corticotropin releasing factor (CRF) was discovered 19 years ago, based on its sequence homology to the parent molecule. Its existence was inferred in the CNS because of anatomical and pharmacological discrepancies between CRF and its two receptor subtypes. Although originally found in the brain, where it has opposing actions to CRF and therefore confers stress-coping mechanisms, Ucn 1 has subsequently been found throughout the periphery including heart, lung, skin, and immune cells. It is now well established that this small peptide is involved in a multitude of physiological and pathophysiological processes, due to its receptor subtype distribution and promiscuity in second messenger signalling pathways. As a result of extensive studies in this field, there are now well over one thousand peer reviewed publications involving Ucn 1. In this review, we intend to highlight some of the less well known actions of Ucn 1 and in particular its role in neuronal cell protection and maintenance of the skeletal system, both by conventional methods of reviewing the literature and using bioinformatics, to highlight further associations between Ucn 1 and disease conditions. Understanding how Ucn 1 works in these tissues, will help to unravel its role in normal and pathophysiological processes. This would ultimately allow the generation of putative medical interventions for the alleviation of important diseases such as Parkinson's disease, arthritis, and osteoporosis.

Telling stories of culture through literature

Grounded on Raymond Williams‘s definition of knowable community as a cultural tool to analyse literary texts, the essay reads the texts D.H.Lawrence wrote while travelling in the Mediterranean (Twilight in Italy, Sea and Sardinia and Etruscan Places) as knowable communities, bringing to the discussion the wide importance of literature not only as an object for aesthetic or textual readings, but also as a signifying practice which tells stories of culture. Departing from some considerations regarding the historical development of the relationship between literature and culture, the essay analyses the ways D. H. Lawrence constructed maps of meaning, where the readers, in a dynamic relation with the texts, apprehend experiences, structures and feelings; putting into perspective Williams‘s theory of culture as a whole way of life, it also analyses the ways the author communicates and organizes these experiences, creating a space of communication and operating at different levels of reality: on the one hand, the reality of the whole way of Italian life, and, on the other hand, the reality of the reader who aspires to make sense and to create an interpretative context where all the information is put, and, also, the reality of the writer in the poetic act of writing. To read these travel writings as knowable communities is to understand them as a form that invents a community with no other existence but that of the literary text. The cultural construction we find in these texts is the result of the selection, and interpretation done by D.H.Lawrence, as well as the product of the author‘s enunciative positions, and of his epistemological and ontological filigrees of existence, structured by the conditions of possibility. In the rearticulation of the text, of the writer and of the reader, in a dynamic and shared process of discursive alliances, we understand that Lawrence tells stories of the Mediterranean through his literary art.

Traduzir Teatro no Estado Novo: Gata em Telhado de Zinco Quente (1959), tradução de Sérgio Guimarães, do original Cat on a Hot Tin Roof (1955), de Tennessee Williams

À luz da viragem cultural dos Estudos de Tradução ocorrida nos anos 80 e tendo em conta a interdisciplinaridade abordada nos campos literário, cultural e histórico pela Manipulation School (Lefevere, Bassnett, Lambert, Hermans e Toury), na esteira de Itamar Even-Zohar com a Teoria dos Polissistemas (1979), a presente dissertação pretende analisar a tradução portuguesa da peça Cat on a Hot Tin Roof (1955), da autoria de Tennessee Williams, intitulada Gata em Telhado de Zinco Quente (1959), de Sérgio Guimarães. Este pode ser um caso representativo de como a tradução para teatro actua na cultura receptora numa perspectiva diatópica, antevendo a dimensão intercultural da tradução para o palco. É ao tradutor que cabe a tarefa de transferir a peça de um sistema linguístico e cultural para outro, conhecendo, se possível, o grau de representabilidade da mesma e o contexto cultural de chegada. Deste modo, é evidenciada a competência artístico-criativa do tradutor teatral que trabalha com o intuito de manter, fidus interpres, as intenções do autor da obra original. No período em que Cat on a Hot Tin Roof foi escrita, ensombrado pelo controlo sociopolítico do Macartismo nos E.U.A. e o contexto em que a tradução foi concretizada, sob a vigência da Ditadura de Salazar, a (auto)censura desempenha um papel fundamental ao moldar a produção literária nos dois sistemas culturais. Numa época em que, mais do que nos dias de hoje, traduzir consistia numa actividade subserviente e secundária, Vasco Morgado, detentor do monopólio de teatros em Lisboa encomendou a Sérgio Guimarães a tradução de uma peça de Tennessee Williams. Com base na teoria desenvolvida por Lawrence Venuti em The Translator’s Invisibility (1995), não é despiciente problematizar, neste estudo de caso, a invisibilidade do tradutor/mediador entre o texto e a representação, abordando simultaneamente as estratégias então necessárias para a peça ser aprovada e posta em cena.

From Consciousness to Knowledge – The Explanatory Power of Revelation

Epistemology in philosophy of mind is a difficult endeavor. Those who believe that our phenomenal life is different from other domains suggest that self-knowledge about phenomenal properties is certain and therefore privileged. Usually, this so called privileged access is explained by the idea that we have direct access to our phenomenal life. This means, in contrast to perceptual knowledge, self-knowledge is non-inferential. It is widely believed that, this kind of directness involves two different senses: an epistemic sense and a metaphysical sense. Proponents of this view often claim that this is due to the fact that we are acquainted with our current experiences. The acquaintance thesis, therefore, is the backbone in justifying privileged access. Unfortunately the whole approach has a profound flaw. For the thesis to work, acquaintance has to be a genuine explanation. Since it is usually assumed that any knowledge relation between judgments and the corresponding objects are merely causal and contingent (e.g. in perception), the proponent of the privileged access view needs to show that acquaintance can do the job. In this thesis, however, I claim that the latter cannot be done. Based on considerations introduced by Levine, I conclude that this approach involves either the introduction of ontologically independent properties or a rather obscure knowledge relation. A proper explanation, however, cannot employ either of the two options. The acquaintance thesis is, therefore, bound to fail. Since the privileged access intuition seems to be vital to epistemology within the philosophy of mind, I will explore alternative justifications. After discussing a number of options, I will focus on the so called revelation thesis. This approach states that by simply having an experience with phenomenal properties, one is in the position to know the essence of those phenomenal properties. I will argue that, after finding a solution for the controversial essence claim, this thesis is a successful replacement explanation which maintains all the virtues of the acquaintance account without necessarily introducing ontologically independent properties or an obscure knowledge relation. The overall solution consists in qualifying the essence claim in the relevant sense, leaving us with an appropriate ontology for phenomenal properties. On the one hand, this avoids employing mysterious independent properties, since this ontological view is physicalist in nature. On the other hand, this approach has the right kind of structure to explain privileged self-knowledge of our phenomenal life. My final conclusion consists in the claim that the privileged access intuition is in fact veridical. It cannot, however, be justified by the popular acquaintance approach, but rather, is explainable by the controversial revelation thesis.

Systematic identification of genomic markers of drug sensitivity in cancer cells.

Clinical responses to anticancer therapies are often restricted to a subset of patients. In some cases, mutated cancer genes are potent biomarkers for responses to targeted agents. Here, to uncover new biomarkers of sensitivity and resistance to cancer therapeutics, we screened a panel of several hundred cancer cell lines--which represent much of the tissue-type and genetic diversity of human cancers--with 130 drugs under clinical and preclinical investigation. In aggregate, we found that mutated cancer genes were associated with cellular response to most currently available cancer drugs. Classic oncogene addiction paradigms were modified by additional tissue-specific or expression biomarkers, and some frequently mutated genes were associated with sensitivity to a broad range of therapeutic agents. Unexpected relationships were revealed, including the marked sensitivity of Ewing's sarcoma cells harbouring the EWS (also known as EWSR1)-FLI1 gene translocation to poly(ADP-ribose) polymerase (PARP) inhibitors. By linking drug activity to the functional complexity of cancer genomes, systematic pharmacogenomic profiling in cancer cell lines provides a powerful biomarker discovery platform to guide rational cancer therapeutic strategies.

Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.

Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140 mm Hg systolic blood pressure or  ≥90 mm Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention.

Arthur A. Schmon Memorial Trophy

This trophy was awarded to the winners of the 'Great Debate' on whether or not university tuition should be free that took place on October 27, 1965 at Brock's Glenridge Campus Auditorium. The affirmative team comprising of Lawrence Winters, Sean Finley, and Gordon Williams were presented with the Arthur A. Schmon Memorial Trophy after successfully arguing that tuition should be free. The trophy was presented by Board of Governor's secretary-treasurer Edward Mitchelson.

Quaternary geology of the Campbellford, Trenton, Consecon, Tweed, Belleville, Wellington, Sydenham, Bath, and Yorkshire Island map-areas, Ontario /

Sediment relationships observed during geological mapping in southeastern Ontario indicate a relatively simple deglaciation history for the area during late Wisconsin time. The ice from the north (part of the Lake Simcoe lobe) and the Lake Ontario ice lobe, which were coalesced during most of late Wisconsin time, initially separated along the crest of the Oak Ridges Moraine. Available data indicate that the Oak Ridges Moraine is composed primarily of sediments pre-late Wisconsin in age capped by late Wisconsin till and interlobate deposits. Retreat of the northern ice was relatively steady and resulted in the deposition of the Dummer Moraines, a facies of the drumlinized till to the south. Retreat of the Lake Ontario ice lobe into the Lake Ontario basin was interrupted by a re-advance which covered the southeastern half of the map area. The northern ice had already retreated from the area by this time. The Lake Ontario lobe was fed through the St. Lawrence Valley, indicating that the Ottawa Valley was ice filled at this time. High level glacial lakes fronted the ice during deglaciation. These waters quickly fell to low levels as the ice retreated from the St. Lawrence Valley, opening lower outlets.

The relationship between creativity and moral judgment

A sample of 50 male and female subjects ranging in age from 12 to 73 were divided into three groups according to the scale of maturity of moral judgment developed by Lawrence Kohlberg. Subjects were also tested on a measure of creativity developed by Torrance after the formulations of Guilford in order to test the hypothesis that the re^- lationship between creativity and maturity of moral judgment is curvilinear. Researchers have failed to develop any working hypothesis concerning the relationship between creativity and moral judgment or postulate any consistent theoretical framework concerning the possible relationship between these two constructs. The empirical investigation involved a scientific testing of a random selection of elementary subjects9 high school adolescents, and creative adults. Tests included Kohlberg8s Moral dilemmas and Guilford's Product Improvement Task. A trend analysis was conducted to reveal whether or not a curvilinear relationship existed between the independent variable (Moral Maturity Stages) and the de~ pe dent variable (creativity performance under each level). Curvilinear trends were observed in two out of four creativity subscales but were not statistically significant. It was concluded that these contradictory findings were due to the relatively small number of subjects tested, the narrow range or moral judgment scores, and the limited conception of creativity defined by the creativity measure used (The Product Improvement Task). It was suggested that an instrument assessing an identity status would be most useful as well as a creativity measure better suited for a theory of creativity essentially developmental in perspective.

Hunter's panoramic guide from Niagara Falls to Quebec /

Reissue of original ed.: Boston : J.P. Jewett ; Cleveland : H.P.B. Jewett, 1857. Cf. TPL 3664.

Gas chromatographic electron capture negative ionization mass spectrometric (GC/ECNI/MS) determination of unique fluorinated compounds in the sediments of Lake Ontario and the effect of high-boiling alcohols (as injection solvents) on chromatographic behaviour of polycyclic aromatic hydrocarbons in gas chromatography

Part I - Fluorinated Compounds A method has been developed for the extraction, concentration, and determination of two unique fluorinated compounds from the sediments of Lake Ontario. These compounds originated from a common industrial landfill, and have been carried to Lake Ontario by the Niagara River. Sediment samples from the Mississauga basin of Lake Ontario have been evaluated for these compounds and a depositional trend was established. The sediments were extracted by accelerated solvent extraction (ASE) and then underwent clean-up, fractionation, solvent exchange, and were concentrated by reduction under nitrogen gas. The concentrated extracts were analyzed by gas chromatography - electron capture negative ionization - mass spectrometry. The depositional profile determined here is reflective of the operation of the landfill and shows that these compounds are still found at concentrations well above background levels. These increased levels have been attributed to physical disturbances of previously deposited contaminated sediments, and probable continued leaching from the dumpsite. Part II - Polycyclic Aromatic Hydrocarbons Gas chromatography/mass spectrometry is the most common method for the determination of polycyclic aromatic hydrocarbons (PAHs) from various matrices. Mass discrimination of high-boiling compounds in gas chromatographic methods is well known. The use of high-boiling injection solvents shows substantial increase in the response of late-eluting peaks. These solvents have an increased efficiently in the transfer of solutes from the injector to the analytical column. The effect of I-butanol, I-pentanol, cyclopentanol, I-hexanol, toluene and n-octane, as injection solvents, was studied. Higher-boiling solvents yield increased response for all PAHs. I -Hexanol is the best solvent, in terms of P AH response, but in this solvent P AHs were more susceptible to chromatographic problems such as peak splitting and tailing. Toluene was found to be the most forgiving solvent in terms of peak symmetry and response. It offered the smallest discrepancies in response, and symmetry over a wide range of initial column temperatures.

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

Upper Lakes Shipping Ltd. fonds 1955-1990, n.d. (non-inclusive)

In March 1931, Captain Bruce Angus was sent to Sarnia by Gordon C. Leitch, general manager of Toronto Elevators. He was sent to inspect the Sarnian to ensure it was still seaworthy. Leitch was a savvy business man, who had been active in the business community for a number of years. Leitch began his career with a partner in the lumber business. When that went under he moved into graineries and worked for the Winnipeg Wheat Pool for 12 years. After Winnipeg he moved to Toronto, which was closer to his home town of Ridgetown, Ontario. In Toronto Leitch became manager of the Toronto branch of the Canadian Wheat Pool. While managing the wheat pools in Toronto Leitch became aware of huge costs associated with shipping the grains from the praries into the Toronto area. He felt that there was no need for such costs and decided to do something to make them better and cheaper for the business. Originally the grain was loaded onto Lakers that would bring the grain from the praries to Lake Huron and Georgian Bay. It was stored there until needed by the Toronto graineries and then hauled across land by either truck or train. The land journey was the most expensive and the one which Leitch wanted to eliminate. This was a fine plan except for 2 obstacles that were quickly overcome. First of all the Welland canals were not large enough to accommodate the large carriers that were bringing in the grain. This was changing as the expansion and widening of the canals was already underway. The second issue was the lack of storage in Toronto for the grain. The grain elevators had been destroyed by fire in the late 1880s and never replaced. Leitch propsed his company built its own storage elevators along the water front to allow not only for easier access to the grain, and more timely production of products. The elevators would aslo create a reduction in shipping costs and an overall more competitoive price for the customers of the grainery. The company refused, so Leitch went elsewhere to friends and contacts within the grain industry. The elevators were built and Leitch quit his job with the Canadian Wheat Pool and became the general manager of the elevators. Although the elevators were built and ready for storage the next issue was filling them. None of the carriers wanted to do business with Leitch because the competition in Georgian Bay threatened to cancel their contracts if they did. Leitch saw no way around this, but to provide his own transportation. This is when he sent Captain Bruce Angus to scout out potential ships. The ship was purchased for $37,000 and after another $30,000 was spent to fix it up, it was ready for business. The need for transportation and the finding of a seaworthy ship, lead to the beginnings of the Northland Steamship Company. The Sarnian proved to not be enough for the business underway. Leitch decided another ship was necessary. He joined forces with James Norris the owner of the Norris Grain Company. He proposed they join forces to create a more economical means of transportating their products.

Great Lakes Waterways Development Association

This archive contains materials relating to the Great Lakes Waterways Development Association. The collection contains correspondence, financial information, clippings, biographical materials, media releases, presentations and publications. The bulk of the materials are correspondence.