Showing papers by "McGill University published in 2001"

The causes of land-use and land-cover change: moving beyond the myths

Abstract: Common understanding of the causes of land-use and land-cover change is dominated by simplifications which, in turn, underlie many environment-development policies. This article tracks some of the major myths on driving forces of land-cover change and proposes alternative pathways of change that are better supported by case study evidence. Cases reviewed support the conclusion that neither population nor poverty alone constitute the sole and major underlying causes of land-cover change worldwide. Rather, peoples’ responses to economic opportunities, as mediated by institutional factors, drive land-cover changes. Opportunities and

Ab initio modeling of quantum transport properties of molecular electronic devices

Abstract: We report on a self-consistent ab initio technique for modeling quantum transport properties of atomic and molecular scale nanoelectronic devices under external bias potentials. The technique is based on density functional theory using norm conserving nonlocal pseudopotentials to define the atomic core and nonequilibrium Green's functions (NEGF's) to calculate the charge distribution. The modeling of an open device system is reduced to a calculation defined on a finite region of space using a screening approximation. The interaction between the device scattering region and the electrodes is accounted for by self-energies within the NEGF formalism. Our technique overcomes several difficulties of doing first principles modeling of open molecular quantum coherent conductors. We apply this technique to investigate single wall carbon nanotubes in contact with an Al metallic electrode. We have studied the current-voltage characteristics of the nanotube-metal interface from first principles. Our results suggest that there are two transmission eigenvectors contributing to the ballistic conductance of the interface, with a total conductance $G\ensuremath{\approx}{G}_{0}$ where ${G}_{0}{=2e}^{2}/h$ is the conductance quanta. This is about half of the expected value for infinite perfect metallic nanotubes.

Maternal care, gene expression, and the transmission of individual differences in stress reactivity across generations.

Abstract: Naturally occurring variations in maternal care alter the expression of genes that regulate behavioral and endocrine responses to stress, as well as hippocampal synaptic development. These effects form the basis for the development of stable, individual differences in stress reactivity and certain forms of cognition. Maternal care also influences the maternal behavior of female offspring, an effect that appears to be related to oxytocin receptor gene expression, and which forms the basis for the intergenerational transmission of individual differences in stress reactivity. Patterns of maternal care that increase stress reactivity in offspring are enhanced by stressors imposed on the mother. These findings provide evidence for the importance of parental care as a mediator of the effects of environmental adversity on neural development.

Spectrofluorometric characterization of dissolved organic matter for indication of precursor organic material and aromaticity

Abstract: We studied the fluorescence properties of fulvic acids isolated from streams and rivers receiving predominantly terrestrial sources of organic material and from lakes with microbial sources of organic material. Microbially derived fulvic acids have fluorophores with a more sharply defined emission peak occurring at lower wavelengths than fluorophores in terrestrially derived fulvic acids. We show that the ratio of the emission intensity at a wavelength of 450 nm to that at 500 nm, obtained with an excitation of 370 nm, can serve as a simple index to distinguish sources of isolated aquatic fulvic acids. In our study, this index has a value of ;1.9 for microbially derived fulvic acids and a value of ;1.4 for terrestrially derived fulvic acids. Fulvic acids isolated from four large rivers in the United States have fluorescence index values of 1.4‐1.5, consistent with predominantly terrestrial sources. For fulvic acid samples isolated from a river, lakes, and groundwaters in a forested watershed, the fluorescence index varied in a manner suggesting different sources for the seepage and streamfed lakes. Furthermore, we identified these distinctive fluorophores in filtered whole water samples from lakes in a desert oasis in Antarctica and in filtered whole water samples collected during snowmelt from a Rocky Mountain stream. The fluorescence index measurement in filtered whole water samples in field studies may augment the interpretation of dissolved organic carbon sources for understanding carbon cycling in aquatic ecosystems.

Systematic Genetic Analysis with Ordered Arrays of Yeast Deletion Mutants

Abstract: In Saccharomyces cerevisiae, more than 80% of the ∼6200 predicted genes are nonessential, implying that the genome is buffered from the phenotypic consequences of genetic perturbation. To evaluate function, we developed a method for systematic construction of double mutants, termed synthetic genetic array (SGA) analysis, in which a query mutation is crossed to an array of ∼4700 deletion mutants. Inviable double-mutant meiotic progeny identify functional relationships between genes. SGA analysis of genes with roles in cytoskeletal organization (BNI1,ARP2, ARC40, BIM1), DNA synthesis and repair (SGS1, RAD27), or uncharacterized functions (BBC1, NBP2) generated a network of 291 interactions among 204 genes. Systematic application of this approach should produce a global map of gene function.

High-resolution haplotype structure in the human genome.

Abstract: Linkage disequilibrium (LD) analysis is traditionally based on individual genetic markers and often yields an erratic, non-monotonic picture, because the power to detect allelic associations depends on specific properties of each marker, such as frequency and population history. Ideally, LD analysis should be based directly on the underlying haplotype structure of the human genome, but this structure has remained poorly understood. Here we report a high-resolution analysis of the haplotype structure across 500 kilobases on chromosome 5q31 using 103 single-nucleotide polymorphisms (SNPs) in a European-derived population. The results show a picture of discrete haplotype blocks (of tens to hundreds of kilobases), each with limited diversity punctuated by apparent sites of recombination. In addition, we develop an analytical model for LD mapping based on such haplotype blocks. If our observed structure is general (and published data suggest that it may be), it offers a coherent framework for creating a haplotype map of the human genome.

Variation in δ15N and δ13C trophic fractionation: Implications for aquatic food web studies

Abstract: Use of stable isotope techniques to quantify food web relationships requires a priori estimates of the enrichment or depletion in δ15N and δ13C values between prey and predator (known as trophic fractionation; hereafter Δδ15N and Δδ13C). We conducted a broad-scale analysis of Δδ15N and Δδ13C from aquatic systems, including three new field estimates. Carnivores had significantly higher Δδ15N values than herbivores. Furthermore, carnivores, invertebrates, and lab-derived estimates were significantly more variable than their counterparts ( f-test, p < 0.00001). Δδ13C was higher for carnivores than for herbivores (p = 0.001), while variances did not differ significantly. Excluding herbivores, the average Δδ15N and Δδ13C were 3.4‰ and 0.8‰, respectively. But even with unbiased fractionation estimates, there is variation in isotopic fractionation that contributes to error in quantitative isotope model outputs. We simulated the error variance in δ15N-based estimates of trophic position and two-source δ13C diet mixing models, explicitly considering the observed variation in Δδ15N and Δδ13C, along with the other potential error sources. The resultant error in trophic position and mixing model outputs was generally minor, provided that primary consumers were used as baseline indicators for estimating trophic position and that end member d13C values in dietary mixing models were sufficiently distinct.

Promotion of Breastfeeding Intervention Trial (PROBIT): a randomized trial in the Republic of Belarus.

Abstract: This paper summarizes the objectives, design, follow-up, and data validation of a cluster-randomized trial of a breastfeeding promotion intervention modeled on the WHO/UNICEF Baby-Friendly Hospital Initiative (BFHI). Thirty-four hospitals and their affiliated polyclinics in the Republic of Belarus were randomized to receive BFHI training of medical, midwifery, and nursing staffs (experimental group) or to continue their routine practices (control group). All breastfeeding mother-infant dyads were considered eligible for inclusion in the study if the infant was singleton, bom at 237 weeks gestation, weighed ≥2500 grams at birth, and had a 5-minute Apgar score ≥5, and neither mother nor infant had a medical condition for which breastfeeding was contraindicated. One experimental and one control site refused to accept their randomized allocation and dropped out of the trial. A total of 17,795 mothers were recruited at the 32 remaining sites, and their infants were followed up at 1, 2, 3, 6, 9, and 12 months of age. To our knowledge, this is the largest randomized trial ever undertaken in area of human milk and lactation. Monitoring visits of all experimental and control maternity hospitals and polyclinics were undertaken prior to recruitment and twice more during recruitment and follow-up to ensure compliance with the randomized allocation. Major study outcomes include the occurrence of ≥1 episode of gastrointestinal infection, ≥2 respiratory infections, and the duration of breastfeeding, and are analyzed according to randomized allocation (“intention to treat”). One of the 32 remaining study sites was dropped from the trial because of apparently falsified follow-up data, as suggested by an unrealistically low incidence of infection and unrealistically long duration of breastfeeding, and as confirmed by subsequent data audit of polyclinic charts and interviews with mothers of 64 randomly-selected study infants at the site. Smaller random audits at each of the remaining sites showed extremely high concordance between the PROBIT data forms and both the polyclinic charts and maternal interviews, with no evident difference in under- or over-reporting in experimental vs control sites. Of the 17,046 infants recruited from the 31 participating study sites, 16,491 (96.7%) completed the study and only 555 (3.3%) were lost to follow-up. PROBIT’s results should help inform decision making for clinicians, hospitals, industry, and governments concerning the support, protection, and promotion of breastfeeding.

Functional Data Analysis

Abstract: Most statistical analyses involve one or more observations taken on each of a number of individuals in a sample, with the aim of making inferences about the general population from which the sample is drawn. In an increasing number of fields, these observations are curves or images. Curves and images are examples of functions, since an observed intensity is available at each point on a line segment, a portion of a plane, or a volume. For this reason, we call observed curves and images ‘functional data,’ and statistical methods for analyzing such data are described by the term ‘functional data analysis’ (FDA). It is the smoothness of the processes generating functional data that differentiates this type of data from more classical multivariate observations. This smoothness means that we can work with the information in the derivatives of functions or images. This article includes several illustrative examples.

Life History, Evolution of

Abstract: The analysis of life history evolution includes any trait that impinges on the reproductive success of an organism. More specifically, life history evolution is typically concerned with the evolution of the age and size at first reproduction, reproductive effort, clutch size, and propagule size. While many analyses focus only on a single trait, it should be remembered that selection acts on fitness (as defined later) and not solely on single traits. Therefore, the appropriate framework for the analysis of life history evolution is the whole suite of traits that interact to determine the fitness of an organism. The analysis of components of fitness is appropriate in many circumstances but the limitations of such an analysis must always be remembered.

A New and Improved Population-Based Canadian Reference for Birth Weight for Gestational Age

Abstract: Background. Existing fetal growth references all suffer from 1 or more major methodologic problems, including errors in reported gestational age, biologically implausible birth weight for gestational age, insufficient sample sizes at low gestational age, single-hospital or other non-population–based samples, and inadequate statistical modeling techniques. Methods. We used the newly developed Canadian national linked file of singleton births and infant deaths for births between 1994 and 1996, for which gestational age is largely based on early ultrasound estimates. Assuming a normal distribution for birth weight at each gestational age, we used the expectation-maximization algorithm to exclude infants with gestational ages that were more consistent with 40-week births than with the observed gestational age. Distributions of birth weight at the corrected gestational ages were then statistically smoothed. Results. The resulting male and female curves provide smooth and biologically plausible means, standard deviations, and percentile cutoffs for defining small- and large-for-gestational-age births. Large-for-gestational age cutoffs (90th percentile) at low gestational ages are considerably lower than those of existing references, whereas small-for-gestational-age cutoffs (10th percentile) postterm are higher. For example, compared with the current World Health Organization reference from California (Williams et al, 1982) and a recently proposed US national reference (Alexander et al, 1996), the 90th percentiles for singleton males at 30 weeks are 1837 versus 2159 and 2710 g. The corresponding 10th percentiles at 42 weeks are 3233 versus 3086 and 2998 g. Conclusions. This new sex-specific, population-based reference should improve clinical assessment of growth in individual newborns, population-based surveillance of geographic and temporal trends in birth weight for gestational age, and evaluation of clinical or public health interventions to enhance fetal growth. fetal growth, birth weight, gestational age, preterm birth, postterm birth.

Extrinsic Rewards and Intrinsic Motivation in Education: Reconsidered Once Again:

Abstract: The finding that extrinsic rewards can undermine intrinsic motivation has been highly controversial since it first appeared (Deci, 1971). A meta-analysis published in this journal (Cameron & Pierce, 1994) concluded that the undermining effect was minimal and largely inconsequential for educational policy. However, a more recent meta-analysis (Deci, Koestner, & Ryan, 1999) showed that the Cameron and Pierce meta-analysis was seriously flawed and that its conclusions were incorrect. This article briefly reviews the results of the more recent meta-analysis, which showed that tangible rewards do indeed have a substantial undermining effect. The meta-analysis provided strong support for cognitive evaluation theory (Deci & Ryan, 1980), which Cameron and Pierce had advocated abandoning. The results are briefly discussed in terms of their relevance for educational practice.

RHex: A Simple and Highly Mobile Hexapod Robot:

Abstract: In this paper, the authors describe the design and control of RHex, a power autonomous, untethered, compliant-legged hexapod robot. RHex has only six actuators—one motor located at each hip— achieving mechanical simplicity that promotes reliable and robust operation in real-world tasks. Empirically stable and highly maneuverable locomotion arises from a very simple clock-driven, open-loop tripod gait. The legs rotate full circle, thereby preventing the common problem of toe stubbing in the protraction (swing) phase. An extensive suite of experimental results documents the robot’s significant “intrinsic mobility”—the traversal of rugged, broken, and obstacle-ridden ground without any terrain sensing or actively controlled adaptation. RHex achieves fast and robust forward locomotion traveling at speeds up to one body length per second and traversing height variations well exceeding its body clearance.

Synchronization and rhythmic processes in physiology

Abstract: Complex bodily rhythms are ubiquitous in living organisms. These rhythms arise from stochastic, nonlinear biological mechanisms interacting with a fluctuating environment. Disease often leads to alterations from normal to pathological rhythm. Fundamental questions concerning the dynamics of these rhythmic processes abound. For example, what is the origin of physiological rhythms? How do the rhythms interact with each other and the external environment? Can we decode the fluctuations in physiological rhythms to better diagnose human disease? And can we develop better methods to control pathological rhythms? Mathematical and physical techniques combined with physiological and medical studies are addressing these questions and are transforming our understanding of the rhythms of life.

Traditional Framingham risk factors fail to fully account for accelerated atherosclerosis in systemic lupus erythematosus.

Abstract: Objective The frequency of coronary heart disease (CHD) and stroke are increased in systemic lupus erythematosus (SLE), but the extent of the increase is uncertain. We sought to determine to what extent the increase could not be explained by common risk factors. Methods The participants at two SLE registries were assessed retrospectively for the baseline level of the Framingham study risk factors and for the presence of vascular outcomes: nonfatal myocardial infarction (MI), death due to CHD, overall CHD (nonfatal MI, death due to CHD, angina pectoris, and congestive heart failure due to CHD), and stroke. For each patient, the probability of the given outcome was estimated based on the individual's risk profile and the Framingham multiple logistic regression model, corrected for observed followup. Ninety-five percent confidence intervals (95% CIs) were estimated by bootstrap techniques. Results Of 296 SLE patients, 33 with a vascular event prior to baseline were excluded. Of the 263 remaining patients, 34 had CHD events (17 nonfatal MIs, 12 CHD deaths) and 16 had strokes over a mean followup period of 8.6 years. After controlling for common risk factors at baseline, the increase in relative risk for these outcomes was 10.1 for nonfatal MI (95% CI 5.8–15.6), 17.0 for death due to CHD (95% CI 8.1–29.7), 7.5 for overall CHD (95% CI 5.1–10.4), and 7.9 for stroke (95% CI 4.0–13.6). Conclusion There is a substantial and statistically significant increase in CHD and stroke in SLE that cannot be fully explained by traditional Framingham risk factors alone.

Intensive Care Delirium Screening Checklist: evaluation of a new screening tool

Abstract: Objective: Delirium in the intensive care unit is poorly defined. Clinical evaluation is difficult in the setting of unstable, often intubated patients. A screening tool may improve the detection of delirium. Method: We created a screening checklist of eight items based on DSM criteria and features of delirium: altered level of consciousness, inattention, disorientation, hallucination or delusion, psychomotor agitation or retardation, inappropriate mood or speech, sleep/wake cycle disturbance, and symptom fluctuation. During 3 months, all patients admitted to a busy medical/surgical intensive care unit were evaluated, and the scale score was compared to a psychiatric evaluation. Results: In 93 patients studied, 15 developed delirium. Fourteen (93%) of them had a score of 4 points or more. This score was also present in 15 (19%) of patients without delirium, 14 of whom had a known psychiatric illness, dementia, a structural neurological abnormality or encephalopathy. A ROC analysis was used to determine the sensitivity and specificity of the screening tool. The area under the ROC curve is 0.9017. Predicted sensitivity is 99% and specificity is 64%. Conclusion: This study suggests that the Intensive Care Delirium Screening Checklist can easily be applied by a clinician or a nurse in a busy critical care setting to screen all patients even when communication is compromised. The tool can be utilized quickly and helps to identify delirious patients. Earlier diagnosis may lead to earlier intervention and better patient care.

Pancreatic Intraepithelial Neoplasia: A New Nomenclature and Classification System for Pancreatic Duct Lesions

Abstract: Proliferative epithelial lesions in the smaller caliber pancreatic ducts and ductules have been the subject of numerous morphologic, clinical, and genetic studies; however, a standard nomenclature and diagnostic criteria for classifying these lesion have not been established. To evaluate the uniform

IL-17 is increased in asthmatic airways and induces human bronchial fibroblasts to produce cytokines.

Abstract: Background: IL-17 is a cytokine that has been reported to be produced by T lymphocytes. In vitro, IL-17 activates fibro-blasts and macrophages for the secretion of GM-CSF, TNF-α, IL-1β, and IL-6. A number of these cytokines are involved in the airway remodeling that is observed within the lungs of asthmatic individuals. Objective: In this study, we investigated the expression of IL-17 in sputum and bronchoalveolar lavage specimens obtained from asthmatic subjects and from nonasthmatic control subjects. Methods: IL-17 was detected through use of immunocytochemistry, in situ hybridization, and Western blot. Bronchial fibroblasts were stimulated with IL-17, and cytokine production and chemokine production were detected through use of ELISA and RT-PCR. Results: Using immunocytochemistry, we demonstrated that the numbers of cells positive for IL-17 are significantly increased in sputum and bronchoalveolar lavage fluids of subjects with asthma in comparison with control subjects ( P P P Conclusion: Our results, which demonstrate for the first time that eosinophils are a potential source of IL-17 within asthmatic airways, suggest that IL-17 might have the potential to amplify inflammatory responses through the release of proinflammatory mediators such as α-chemokines. (J Allergy Clin Immunol 2001;108:430-8.)

Wisconsin Card Sorting Revisited: Distinct Neural Circuits Participating in Different Stages of the Task Identified by Event-Related Functional Magnetic Resonance Imaging

Abstract: The Wisconsin Card Sorting Task (WCST) has been used to assess dysfunction of the prefrontal cortex and basal ganglia. Previous brain imaging studies have focused on identifying activity related to the set-shifting requirement of the WCST. The present study used event-related functional magnetic resonance imaging (fMRI) to study the pattern of activation during four distinct stages in the performance of this task. Eleven subjects were scanned while performing the WCST and a control task involving matching two identical cards. The results demonstrated specific involvement of different prefrontal areas during different stages of task performance. The mid-dorsolateral prefrontal cortex (area 9/46) increased activity while subjects received either positive or negative feedback, that is at the point when the current information must be related to earlier events stored in working memory. This is consistent with the proposed role of the mid-dorsolateral prefrontal cortex in the monitoring of events in working memory. By contrast, a cortical basal ganglia loop involving the mid-ventrolateral prefrontal cortex (area 47/12), caudate nucleus, and mediodorsal thalamus increased activity specifically during the reception of negative feedback, which signals the need for a mental shift to a new response set. The posterior prefrontal cortex response was less specific; increases in activity occurred during both the reception of feedback and the response period, indicating a role in the association of specific actions to stimuli. The putamen exhibited increased activity while matching after negative feedback but not while matching after positive feedback, implying greater involvement during novel than routine actions.

Adverse Events Associated With Prescription Drug Cost-Sharing Among Poor and Elderly Persons

Abstract: ContextRising costs of medications and inequities in access have sparked calls for drug policy reform in the United States and Canada. Control of drug expenditures by prescription cost-sharing for elderly persons and poor persons is a contentious issue because little is known about the health impact in these subgroups.ObjectivesTo determine (1) the impact of introducing prescription drug cost-sharing on use of essential and less essential drugs among elderly persons and welfare recipients and (2) rates of emergency department (ED) visits and serious adverse events associated with reductions in drug use before and after policy implementation.Design and SettingInterrupted time-series analysis of data from 32 months before and 17 months after introduction of a prescription coinsurance and deductible cost-sharing policy in Quebec in 1996. Separate 10-month prepolicy control and postpolicy cohort studies were conducted to estimate the impact of the drug reform on adverse events.ParticipantsA random sample of 93 950 elderly persons and 55 333 adult welfare medication recipients.Main Outcome MeasuresMean daily number of essential and less essential drugs used per month, ED visits, and serious adverse events (hospitalization, nursing home admission, and mortality) before and after policy introduction.ResultsAfter cost-sharing was introduced, use of essential drugs decreased by 9.12% (95% confidence interval [CI], 8.7%-9.6%) in elderly persons and by 14.42% (95% CI, 13.3%-15.6%) in welfare recipients; use of less essential drugs decreased by 15.14% (95% CI, 14.4%-15.9%) and 22.39% (95% CI, 20.9%-23.9%), respectively. The rate (per 10 000 person-months) of serious adverse events associated with reductions in use of essential drugs increased from 5.8 in the prepolicy control cohort to 12.6 in the postpolicy cohort in elderly persons (a net increase of 6.8 [95% CI, 5.6-8.0]) and from 14.7 to 27.6 in welfare recipients (a net increase of 12.9 [95% CI, 10.2-15.5]). Emergency department visit rates related to reductions in the use of essential drugs also increased by 14.2 (95% CI, 8.5-19.9) per 10 000 person-months in elderly persons (prepolicy control cohort, 32.9; postpolicy cohort, 47.1) and by 54.2 (95% CI, 33.5-74.8) among welfare recipients (prepolicy control cohort, 69.6; postpolicy cohort, 123.8). These increases were primarily due to an increase in the proportion of recipients who reduced their use of essential drugs. Reductions in the use of less essential drugs were not associated with an increase in risk of adverse events or ED visits.ConclusionsIn our study, increased cost-sharing for prescription drugs in elderly persons and welfare recipients was followed by reductions in use of essential drugs and a higher rate of serious adverse events and ED visits associated with these reductions.

Insulin-like growth factor-I receptor signaling and resistance to trastuzumab (Herceptin)

Abstract: Background Trastuzumab (Herceptin), an anti-HER2/neu receptor monoclonal antibody that inhibits growth of ErbB2-overexpressing breast cancer, is used to treat such cancers. Development of resistance to trastuzumab, however, is common. We investigated whether insulin-like growth factor-I (IGF-I), which activates cell survival signals, interferes with the growth-inhibitory action of trastuzumab. Methods MCF-7/HER2-18 and SKBR3 human breast cancer models were used to assess cell proliferation, colony formation in soft agar, and cell cycle parameters. Throughout, we used trastuzumab at a dose of 10 microg/mL and IGF-I at a dose of 40 ng/mL. All statistical tests were two-sided. Results Trastuzumab inhibited the growth of MCF-7/HER2-18 cells, which overexpress HER2/neu receptors and express IGF-I receptors (IGF-IRs), only when IGF-IR signaling was minimized. For example, in 1% fetal bovine serum (FBS), trastuzumab reduced cell proliferation by 42% (P =.002); however, in 10% FBS or IGF-I, trastuzumab had no effect on proliferation. In SKBR3 cells, which overexpress HER2/neu receptor but express few IGF-IRs, trastuzumab reduced proliferation by 42% (P =.008) regardless of IGF-I concentration. When SKBR3 cells were genetically altered to overexpress IGF-IRs and cultured with IGF-I, trastuzumab had no effect on proliferation. However, the addition of IGF-binding protein-3, which decreased IGF-IR signaling, restored trastuzumab-induced growth inhibition. Conclusions In breast cancer cell models that overexpress HER2/neu, an increased level of IGF-IR signaling appears to interfere with the action of trastuzumab. Thus, strategies that target IGF-IR signaling may prevent or delay development of resistance to trastuzumab.

Hierarchical phosphorylation of the translation inhibitor 4E-BP1

Abstract: In most instances, translation is regulated at the initiation phase, when a ribosome is recruited to the 5′ end of an mRNA. The eIF4E-binding proteins (4E-BPs) interdict translation initiation by binding to the translation factor eIF4E, and preventing recruitment of the translation machinery to mRNA. The 4E-BPs inhibit translation in a reversible manner. Hypophosphorylated 4E-BPs interact avidly with eIF4E, whereas 4E-BP hyperphosphorylation, elicited by stimulation of cells with hormones, cytokines, or growth factors, results in an abrogation of eIF4E-binding activity. We reported previously that phosphorylation of 4E-BP1 on Thr 37 and Thr 46 is relatively insensitive to serum deprivation and rapamycin treatment, and that phosphorylation of these residues is required for the subsequent phosphorylation of a set of unidentified serum-responsive sites. Here, using mass spectrometry, we identify the serum-responsive, rapamycin-sensitive sites as Ser 65 and Thr 70. Utilizing a novel combination of two-dimensional isoelectric focusing/SDS-PAGE and Western blotting with phosphospecific antibodies, we also establish the order of 4E-BP1 phosphorylation in vivo; phosphorylation of Thr 37/Thr 46 is followed by Thr 70 phosphorylation, and Ser 65 is phosphorylated last. Finally, we show that phosphorylation of Ser 65 and Thr 70 alone is insufficient to block binding to eIF4E, indicating that a combination of phosphorylation events is necessary to dissociate 4E-BP1 from eIF4E.

Suppression of hadrons with large transverse momentum in central Au + Au collisions at √sNN = 130 GeV

Abstract: Transverse momentum spectra for charged hadrons and for neutral pions in the range 1 Gev/c < P-T < 5 GeV/c have been measured by the PHENIX experiment at RHIC in Au + Au collisions at rootS(NN) = 130 GeV. At high p(T) the spectra from peripheral nuclear collisions are consistent with scaling the spectra from p + p collisions by the average number of binary nucleon-nucleon collisions. The spectra from central collisions are significantly suppressed when compared to the binary-scaled p + p expectation, and also when compared to similarly binary-scaled peripheral collisions, indicating a novel nuclear-medium effect in central nuclear collisions at RHIC energies.

Genetic variation in the 5q31 cytokine gene cluster confers susceptibility to Crohn disease.

Abstract: Linkage disequilibrium (LD) mapping provides a powerful method for fine-structure localization of rare disease genes, but has not yet been widely applied to common disease1. We sought to design a systematic approach for LD mapping and apply it to the localization of a gene (IBD5) conferring susceptibility to Crohn disease. The key issues are: (i) to detect a significant LD signal (ii) to rigorously bound the critical region and (iii) to identify the causal genetic variant within this region. We previously mapped the IBD5 locus to a large region spanning 18 cM of chromosome 5q31 (P<10−4). Using dense genetic maps of microsatellite markers and single-nucleotide polymorphisms (SNPs) across the entire region, we found strong evidence of LD. We bound the region to a common haplotype spanning 250 kb that shows strong association with the disease (P<2×10−7) and contains the cytokine gene cluster. This finding provides overwhelming evidence that a specific common haplotype of the cytokine region in 5q31 confers susceptibility to Crohn disease. However, genetic evidence alone is not sufficient to identify the causal mutation within this region, as strong LD across the region results in multiple SNPs having equivalent genetic evidence—each consistent with the expected properties of the IBD5 locus. These results have important implications for Crohn disease in particular and LD mapping in general.

Anemia as an independent prognostic factor for survival in patients with cancer: a systemic, quantitative review.

Abstract: BACKGROUND Anemia is common in cancer patients, although the prevalence is influenced both by the type of malignancy and the choice of treatment. Individual studies have compared the survival of patients with and without anemia and have shown reduced survival times in patients with various malignancies, including carcinoma of the lung, cervix, head and neck, prostate, lymphoma, and multiple myeloma. The objective of this study was to systematically review, to summarize, and to obtain an overall estimate of the effect of anemia on survival in patients with malignant disease. METHODS A comprehensive literature review was carried out using the MEDLINE data base and reviewing the reference lists from published studies. Two hundred papers were identified. Of these, 60 papers that reported the survival of cancer patients according to either hemoglobin levels or the presence of anemia were included. Among these papers, 25% related to patients with lung carcinoma, 17% related to patients with head and neck carcinoma, 12% related to patients with multiple myeloma, 10% related to patients with prostate carcinoma, 8% related to patients with cervicouterine carcinoma, 7% related to patients with leukemia, 5% related to patients with lymphoma, and 16% related to patients with other types of malignancies. RESULTS The relative risk of death increased by 19% (95% confidence interval, 10–29%) in anemic patients with lung carcinoma, by 75% (37–123%) in anemic patients with head and neck carcinoma, by 47% (21–78%) in anemic patients with prostate carcinoma, and by 67% (30–113%) in anemic patients with lymphoma. The overall estimate increase in risk was 65% (54–77%). CONCLUSIONS Anemia is associated with shorter survival times for patients with lung carcinoma, cervicouterine carcinoma, head and neck carcinoma, prostate carcinoma, lymphoma, and multiple myeloma. Cancer 2001;91:2214–21. © 2001 American Cancer Society.

AAPM protocol for 40–300 kV x-ray beam dosimetry in radiotherapy and radiobiology

Abstract: The American Association of Physicists in Medicine (AAPM) presents a new protocol, developed by the Radiation Therapy Committee Task Group 61, for reference dosimetry of low- and medium-energy x rays for radiotherapy and radiobiology (40 kV or = 100 kV (the "in-phantom" method). The in-phantom method is not recommended for tube potentials < 100 kV. Guidelines are provided to determine the dose at other points in water and the dose at the surface of other biological materials of interest. The protocol is based on an up-to-date data set of basic dosimetry parameters, which produce consistent dose values for the two methods recommended. Estimates of uncertainties on the final dose values are also presented.

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.