Showing papers by "McGill University published in 2000"

The genome sequence of Drosophila melanogaster

Abstract: The fly Drosophila melanogaster is one of the most intensively studied organisms in biology and serves as a model system for the investigation of many developmental and cellular processes common to higher eukaryotes, including humans. We have determined the nucleotide sequence of nearly all of the approximately 120-megabase euchromatic portion of the Drosophila genome using a whole-genome shotgun sequencing strategy supported by extensive clone-based sequence and a high-quality bacterial artificial chromosome physical map. Efforts are under way to close the remaining gaps; however, the sequence is of sufficient accuracy and contiguity to be declared substantially complete and to support an initial analysis of genome structure and preliminary gene annotation and interpretation. The genome encodes approximately 13,600 genes, somewhat fewer than the smaller Caenorhabditis elegans genome, but with comparable functional diversity.

The diversity–stability debate

Abstract: There exists little doubt that the Earth's biodiversity is declining. The Nature Conservancy, for example, has documented that one-third of the plant and animal species in the United States are now at risk of extinction. The problem is a monumental one, and forces us to consider in depth how we expect ecosystems, which ultimately are our life-support systems, to respond to reductions in diversity. This issue--commonly referred to as the diversity-stability debate--is the subject of this review, which synthesizes historical ideas with recent advances. Both theory and empirical evidence agree that we should expect declines in diversity to accelerate the simplification of ecological communities.

Voice-selective areas in human auditory cortex

Abstract: The human voice contains in its acoustic structure a wealth of information on the speaker's identity and emotional state which we perceive with remarkable ease and accuracy. Although the perception of speaker-related features of voice plays a major role in human communication, little is known about its neural basis. Here we show, using functional magnetic resonance imaging in human volunteers, that voice-selective regions can be found bilaterally along the upper bank of the superior temporal sulcus (STS). These regions showed greater neuronal activity when subjects listened passively to vocal sounds, whether speech or non-speech, than to non-vocal environmental sounds. Central STS regions also displayed a high degree of selectivity by responding significantly more to vocal sounds than to matched control stimuli, including scrambled voices and amplitude-modulated noise. Moreover, their response to stimuli degraded by frequency filtering paralleled the subjects' behavioural performance in voice-perception tasks that used these stimuli. The voice-selective areas in the STS may represent the counterpart of the face-selective areas in human visual cortex; their existence sheds new light on the functional architecture of the human auditory cortex.

Heat-shock protein 70 inhibits apoptosis by preventing recruitment of procaspase-9 to the Apaf-1 apoptosome.

Abstract: The cellular-stress response can mediate cellular protection through expression of heat-shock protein (Hsp) 70, which can interfere with the process of apoptotic cell death. Stress-induced apoptosis proceeds through a defined biochemical process that involves cytochrome c, Apaf-1 and caspase proteases. Here we show, using a cell-free system, that Hsp70 prevents cytochrome c/dATP-mediated caspase activation, but allows the formation of Apaf-1 oligomers. Hsp70 binds to Apaf-1 but not to procaspase-9, and prevents recruitment of caspases to the apoptosome complex. Hsp70 therefore suppresses apoptosis by directly associating with Apaf-1 and blocking the assembly of a functional apoptosome.

A mesoscale phytoplankton bloom in the polar Southern Ocean stimulated by iron fertilization

Abstract: Changes in iron supply to oceanic plankton are thought to have a significant effect on concentrations of atmospheric carbon dioxide by altering rates of carbon sequestration, a theory known as the 'iron hypothesis' For this reason, it is important to understand the response of pelagic biota to increased iron supply Here we report the results of a mesoscale iron fertilization experiment in the polar Southern Ocean, where the potential to sequester iron-elevated algal carbon is probably greatest Increased iron supply led to elevated phytoplankton biomass and rates of photosynthesis in surface waters, causing a large drawdown of carbon dioxide and macronutrients, and elevated dimethyl sulphide levels after 13 days This drawdown was mostly due to the proliferation of diatom stocks But downward export of biogenic carbon was not increased Moreover, satellite observations of this massive bloom 30 days later, suggest that a sufficient proportion of the added iron was retained in surface waters Our findings demonstrate that iron supply controls phytoplankton growth and community composition during summer in these polar Southern Ocean waters, but the fate of algal carbon remains unknown and depends on the interplay between the processes controlling export, remineralisation and timescales of water mass subduction

Physicians and the pharmaceutical industry: is a gift ever just a gift?

Abstract: ContextControversy exists over the fact that physicians have regular contact with the pharmaceutical industry and its sales representatives, who spend a large sum of money each year promoting to them by way of gifts, free meals, travel subsidies, sponsored teachings, and symposia.ObjectiveTo identify the extent of and attitudes toward the relationship between physicians and the pharmaceutical industry and its representatives and its impact on the knowledge, attitudes, and behavior of physicians.Data SourcesA MEDLINE search was conducted for English-language articles published from 1994 to present, with review of reference lists from retrieved articles; in addition, an Internet database was searched and 5 key informants were interviewed.Study SelectionA total of 538 studies that provided data on any of the study questions were targeted for retrieval, 29 of which were included in the analysis.Data ExtractionData were extracted by 1 author. Articles using an analytic design were considered to be of higher methodological quality.Data SynthesisPhysician interactions with pharmaceutical representatives were generally endorsed, began in medical school, and continued at a rate of about 4 times per month. Meetings with pharmaceutical representatives were associated with requests by physicians for adding the drugs to the hospital formulary and changes in prescribing practice. Drug company–sponsored continuing medical education (CME) preferentially highlighted the sponsor's drug(s) compared with other CME programs. Attending sponsored CME events and accepting funding for travel or lodging for educational symposia were associated with increased prescription rates of the sponsor's medication. Attending presentations given by pharmaceutical representative speakers was also associated with nonrational prescribing.ConclusionThe present extent of physician-industry interactions appears to affect prescribing and professional behavior and should be further addressed at the level of policy and education.

A Noncooperative Model of Network Formation

Abstract: We present an approach to network formation based on the notion that social networks are formed by individual decisions that trade off the costs of forming and maintaining links against the potential rewards from doing so. We suppose that a link with another agent allows access, in part and in due course, to the benefits available to the latter via his own links. Thus individual links generate externalities whose value depends on the level of decay/delay associated with indirect links. A distinctive aspect of our approach is that the costs of link formation are incurred only by the person who initiates the link. This allows us to formulate the network formation process as a noncooperative game.

Single dose radiosurgical treatment of recurrent previously irradiated primary brain tumors and brain metastases: final report of RTOG protocol 90-05.

Abstract: Purpose: To determine the maximum tolerated dose of single fraction radiosurgery in patients with recurrent previously irradiated primary brain tumors and brain metastases. Methods and Materials: Adults with cerebral or cerebellar solitary non-brainstem tumors ≤ 40 mm in maximum diameter were eligible. Initial radiosurgical doses were 18 Gy for tumors ≤ 20 mm, 15 Gy for those 21–30 mm, and 12 Gy for those 31–40 mm in maximum diameter. Dose was prescribed to the 50–90% isodose line. Doses were escalated in 3 Gy increments providing the incidence of irreversible grade 3 (severe) or any grade 4 (life threatening) or grade 5 (fatal) Radiation Therapy Oncology Group (RTOG) central nervous system (CNS) toxicity (unacceptable CNS toxicity) was Results: Between 1990–1994, 156 analyzable patients were entered, 36% of whom had recurrent primary brain tumors (median prior dose 60 Gy) and 64% recurrent brain metastases (median prior dose 30 Gy). The maximum tolerated doses were 24 Gy, 18 Gy, and 15 Gy for tumors ≤ 20 mm, 21–30 mm, and 31–40 mm in maximum diameter, respectively. However, for tumors Conclusions: The maximum tolerated doses of single fraction radiosurgery were defined for this population of patients as 24 Gy, 18 Gy, and 15 Gy for tumors ≤ 20 mm, 21–30 mm, and 31–40 mm in maximum diameter. Unacceptable CNS toxicity was more likely in patients with larger tumors, whereas local tumor control was most dependent on the type of recurrent tumor and the treatment unit.

Differential Games in Economics and Management Science

Abstract: A comprehensive, self-contained survey of the theory and applications of differential games, one of the most commonly used tools for modelling and analysing economics and management problems which are characterised by both multiperiod and strategic decision making. Although no prior knowledge of game theory is required, a basic knowledge of linear algebra, ordinary differential equations, mathematical programming and probability theory is necessary. Part One presents the theory of differential games, starting with the basic concepts of game theory and going on to cover control theoretic models, Markovian equilibria with simultaneous play, differential games with hierarchical play, trigger strategy equilibria, differential games with special structures, and stochastic differential games. Part Two offers applications to capital accumulation games, industrial organization and oligopoly games, marketing, resources and environmental economics.

Use of oral corticosteroids and risk of fractures.

Abstract: Treatment with systemic corticosteroids is known to increase the risk of fractures but little is known of the fracture risks associated with inhaled corticosteroids. A retrospective cohort study was conducted using a large UK primary care database (the General Practice Research Database [GPRD]). Inhaled corticosteroid users aged 18 years or older were compared with matched control patients and to a group of noncorticosteroid bronchodilator users. Patients with concomitant use of systemic corticosteroids were excluded. The study comprised 170,818 inhaled corticosteroid users, 108,786 bronchodilator users, and 170,818 control patients. The average age was 45.1 years in the inhaled corticosteroid, 49.3 years in the bronchodilator, and 45.2 years in the control groups. In the inhaled corticosteroid cohort, 54.5% were female. The relative rates (RRs) of nonvertebral, hip, and vertebral fractures during inhaled corticosteroid treatment compared with control were 1.15 (95% CI, 1.10-1.20), 1.22 (95% CI, 1.04-1.43), and 1.51 (95% CI, 1.22-1.85), respectively. No differences were found between the inhaled corticosteroid and bronchodilator groups (nonvertebral fracture RR = 1.00; 95% CI, 0.94-1.06). The rates of nonvertebral fractures among users of budesonide (RR = 0.95; 95% CI, 0.85-1.07) and fluticasone propionate (RR = 1.03; 95% CI, 0.71-1.49) were similar to the rate determined for users of beclomethasone dipropionate. We conclude that users of inhaled corticosteroids have an increased risk of fracture, particularly at the hip and spine. However, this excess risk may be related more to the underlying respiratory disease than to inhaled corticosteroid.

Maternal care, hippocampal synaptogenesis and cognitive development in rats.

Abstract: We report that variations in maternal care in the rat promote hippocampal synaptogenesis and spatial learning and memory through systems known to mediate experience-dependent neural development. Thus, the offspring of mothers that show high levels of pup licking and grooming and arched-back nursing showed increased expression of NMDA receptor subunit and brain-derived neurotrophic factor (BDNF) mRNA, increased cholinergic innervation of the hippocampus and enhanced spatial learning and memory. A cross-fostering study provided evidence for a direct relationship between maternal behavior and hippocampal development, although not all neonates were equally sensitive to variations in maternal care.

Continuous intravenous epoprostenol for pulmonary hypertension due to the scleroderma spectrum of disease. A randomized, controlled trial.

Abstract: Continuous epoprostenol therapy improves exercise capacity and cardiopulmonary hemodynamics in patients with pulmonary hypertension due to the scleroderma spectrum of disease

Receptors for Dopamine and Somatostatin: Formation of Hetero-Oligomers with Enhanced Functional Activity

Abstract: Somatostatin and dopamine are two major neurotransmitter systems that share a number of structural and functional characteristics. Somatostatin receptors and dopamine receptors are colocalized in neuronal subgroups, and somatostatin is involved in modulating dopamine-mediated control of motor activity. However, the molecular basis for such interaction between the two systems is unclear. Here, we show that dopamine receptor D2R and somatostatin receptor SSTR5 interact physically through hetero-oligomerization to create a novel receptor with enhanced functional activity. Our results provide evidence that receptors from different G protein (heterotrimeric guanine nucleotide binding protein)–coupled receptor families interact through oligomerization. Such direct intramembrane association defines a new level of molecular crosstalk between related G protein–coupled receptor subfamilies.

Exploiting tumor-specific defects in the interferon pathway with a previously unknown oncolytic virus.

Abstract: Interferons are circulating factors that bind to cell surface receptors, activating a signaling cascade, ultimately leading to both an antiviral response and an induction of growth inhibitory and/or apoptotic signals in normal and tumor cells. Attempts to exploit the ability of interferons to limit the growth of tumors in patients has met with limited results because of cancer-specific mutations of gene products in the interferon pathway. Although interferon-non-responsive cancer cells may have acquired a growth/survival advantage over their normal counterparts, they may have simultaneously compromised their antiviral response. To test this, we used vesicular stomatitis virus (VSV), an enveloped, negative-sense RNA virus exquisitely sensitive to treatment with interferon. VSV rapidly replicated in and selectively killed a variety of human tumor cell lines even in the presence of doses of interferon that completely protected normal human primary cell cultures. A single intratumoral injection of VSV was effective in reducing the tumor burden of nude mice bearing subcutaneous human melanoma xenografts. Our results support the use of VSV as a replication-competent oncolytic virus and demonstrate a new strategy for the treatment of interferon non-responsive tumors.

Socio-economic disparities in pregnancy outcome: why do the poor fare so poorly?

Abstract: In this paper, we review the evidence bearing on socio-economic disparities in pregnancy outcome, focusing on aetiological factors mediating the disparities in intrauterine growth restriction (IUGR) and preterm birth. We first summarise what is known about the attributable determinants of IUGR and preterm birth, emphasising their quantitative contributions (aetiological fractions) from a public health perspective. We then review studies relating these determinants to socio-economic status and, combined with the evidence about their aetiological fractions, reach some tentative conclusions about their roles as mediators of the socio-economic disparities. Cigarette smoking during pregnancy appears to be the most important mediating factor for IUGR, with low gestational weight gain and short stature also playing substantial roles. For preterm birth, socio-economic gradients in bacterial vaginosis and cigarette smoking appear to explain some of the socio-economic disparities; psychosocial factors may prove even more important, but their aetiological links with preterm birth require further clarification. Research that identifies and quantifies the causal pathways and mechanisms whereby social disadvantage leads to higher risks of IUGR and preterm birth may eventually help to reduce current disparities and improve pregnancy outcome across the entire socio-economic spectrum.

Mechanisms of sodium pump regulation

Abstract: The Na(+)-K(+)-ATPase, or sodium pump, is the membrane-bound enzyme that maintains the Na(+) and K(+) gradients across the plasma membrane of animal cells. Because of its importance in many basic and specialized cellular functions, this enzyme must be able to adapt to changing cellular and physiological stimuli. This review presents an overview of the many mechanisms in place to regulate sodium pump activity in a tissue-specific manner. These mechanisms include regulation by substrates, membrane-associated components such as cytoskeletal elements and the gamma-subunit, and circulating endogenous inhibitors as well as a variety of hormones, including corticosteroids, peptide hormones, and catecholamines. In addition, the review considers the effects of a range of specific intracellular signaling pathways involved in the regulation of pump activity and subcellular distribution, with particular consideration given to the effects of protein kinases and phosphatases.

Missing Surface Inflection or Impairment in second language acquisition? Evidence from tense and agreement

Abstract: In this article, two accounts of the variable use of inflection in adult second language (L2) acquisition are examined. The Missing Surface Inflection Hypothesis (MSIH) proposes that L2 learners have unconscious knowledge of the functional projections and features underlying tense and agreement. However, learners sometimes have a problem with realization of surface morphology, such that they resort to non-finite forms (e.g. Haznedar and Schwartz, 1997; Prevost and White, 1999). The Impaired Representation Hypothesis (IRH) claims that L2 inflection is essentially impaired, due to lack of functional categories, features or feature strength (e.g. Eubank, 1993/94; Meisel, 1997). These views make different predictions for adult L2 acquisition. Spontaneous production data from two adult learners of French and two adult learners of German are examined. The data show that finite forms do not occur in non-finite contexts, that learners exhibit syntactic reflexes of finiteness and that inflected forms largely show ...

Impact of Culture on Human Resource Management Practices: A 10‐Country Comparison

Abstract: Le Mode`le de Culture Fit explique la manie`re dont l’environnement socio-culturel influence la culture interne au travail et les pratiques de la direction des ressources humaines. Ce mode`le a e´te´ teste´ sur 2003 salarie´s d’entreprises prive´es dans 10 pays. Les participants ont rempli un questionnaire de 57 items, destine´ a` mesurer les perceptions de la direction sur 4 dimensions socio-culturelles, 6 dimensions de culture interne au travail, et les pratiques HRM (Management des Ressources Humaines) dans 3 zones territoiriales. Une analyse ponde´re´e par re´gressions multiples, au niveau individuel, a montre´ que les directeurs qui caracte´risaient leurs environnement socio-culturel de fac¸on fataliste, supposaient aussi que les employe´s n’e´taient pas malle´ables par nature. Ces directeurs ne pratiquaient pas l’enrichissement des postes et donnaient tout pouvoir au controle et a` la re´mune´ration en fonction des performances. Les directeurs qui appre´ciaient une grande loyaute´ des employe´s supposaient qu’ils remplissent entre eux des obligations re´ciproques et s’engagaient dans la voie donnant pouvoir aux pratiques HRM. Les directeurs qui percevaient le paternalisme et une forte distance de l’autorite´ dans leur environnement socio-culturel, supposaient une re´activite´ des employe´s, et en outre ne pourvoyaient pas a` l’enrichissement des postes et a` la de´le´gation. Des mode`les spe´cifiques a` la culture qui mettent en relation ces 3 groupes de variables ainsi que les applications de ces recherches pour la psychologie industrielles trans-culturellesont e´te´ de´battus.

Social support, depression, and mortality during the first year after myocardial infarction.

Abstract: Background—We previously reported that depression after myocardial infarction (MI) increases the long-term risk of cardiac mortality. Other research suggests that social support may also influence prognosis. This article examines the interrelationships between baseline depression and social support in terms of cardiac prognosis and changes in depression symptoms over the first post-MI year. Methods and Results—For this study, 887 patients completed the Beck Depression Inventory (BDI) and the Perceived Social Support Scale (PSSS) at about 7 days after MI. Some 32% had BDIs ≥10, indicating mild to moderate depression. One-year survival status was determined for all patients. Follow-up interviews, including the BDI, were conducted with 89% of survivors. There were 39 deaths (35 cardiac). Elevated BDI scores were related to cardiac mortality (P=0.0006), but PSSS scores and other measures of social support were not. There was a significant interaction between depression and the PSSS (P=0.016). The relationship...

Discourse as a Strategic Resource

Abstract: In this article, we outline a model of how discourse can be mobilized as a strategic resource. The model consists of three circuits. First, in circuits of activity, individuals attempt to introduce new discursive statements, through the use of symbols, narratives, metaphors, etc. aimed at evoking concepts to create particular objects. These activities must intersect with circuits of performativity. This occurs when, for example, concepts are contextually embedded and have meaning for other actors; when symbols, narratives and metaphors possess receptivity; and when the subject position of the enunciator warrants voice. Third, when these two circuits intersect, connectivity occurs as the new discursive statements `take'. Using an illustrative example of an international NGO operating in Palestine, we show how an individual brought about strategic change by engaging in discursive activity.

Autoantibodies to ganglionic acetylcholine receptors in autoimmune autonomic neuropathies

Abstract: Background Idiopathic autonomic neuropathy is a severe, subacute disorder with a presumed autoimmune basis. It is indistinguishable from the subacute autonomic neuropathy that may accompany lung cancer or other tumors. Autoantibodies specific for nicotinic acetylcholine receptors in the autonomic ganglia are potentially pathogenic and may serve as serologic markers of various forms of autoimmune autonomic neuropathy. Methods We tested serum from 157 patients with a variety of types of dysautonomia. Immunoprecipitation assays with iodine-125–labeled epibatidine and solubilized human neuroblastoma acetylcholine receptors were used to detect autoantibodies that bound to or blocked ganglionic receptors. Results Ganglionic-receptor–binding antibodies were found in 19 of 46 patients with idiopathic or paraneoplastic autonomic neuropathy (41 percent), in 6 of 67 patients with postural tachycardia syndrome, idiopathic gastrointestinal dysmotility, or diabetic autonomic neuropathy (9 percent), and in none of 44 pa...

Computational principles of mobile robotics

Abstract: Mobile robotics is a multidisciplinary field involving both computer science and engineering. Addressing the design of automated systems, it lies at the intersection of artificial intelligence, computational vision, and robotics. This textbook for advanced undergraduates and graduate students emphasizes algorithms for a range of strategies for locomotion, sensing, and reasoning. It concentrates on wheeled and legged mobile robots but discusses a variety of other propulsion systems. The new edition includes advances in robotics and intelligent machines over the last ten years, including significant coverage of SLAM (simultaneous localization and mapping) and multi-robot systems. It includes additional mathematical background and an extensive list of sample problems. Various mathematical techniques that were assumed in the first edition are now briefly introduced in appendices at the end of the text to make the book more self-contained. Researchers as well as students in the field of mobile robotics will appreciate this comprehensive treatment of state-of-the-art methods and key technologies.