CiteULike: Author Pepin

Stromal gene expression predicts clinical outcome in breast cancer

Greg Finak — 2008-05-07T19:39:29-00:00

Nat Med, Vol. 14, No. 5. (May 2008), pp. 518-527.

Laser-Induced Electron Tunneling and Diffraction

M Meckel — 2008-06-20T01:51:35-00:00

Science, Vol. 320, No. 5882. (13 June 2008), pp. 1478-1482.

Molecular structure is usually determined by measuring the diffraction pattern the molecule impresses on x-rays or electrons. We used a laser field to extract electrons from the molecule itself, accelerate them, and in some cases force them to recollide with and diffract from the parent ion, all within a fraction of a laser period. Here, we show that the momentum distribution of the extracted electron carries the fingerprint of the highest occupied molecular orbital, whereas the elastically scattered electrons reveal the position of the nuclear components of the molecule. Thus, in one comprehensive technology, the photoelectrons give detailed information about the electronic orbital and the position of the nuclei. 10.1126/science.1157980

The male-specific region of the human Y chromosome is a mosaic of discrete sequence classes.

H Skaletsky — 2005-12-28T09:38:14-00:00

Nature, Vol. 423, No. 6942. (19 June 2003), pp. 825-837.

The male-specific region of the Y chromosome, the MSY, differentiates the sexes and comprises 95% of the chromosome's length. Here, we report that the MSY is a mosaic of heterochromatic sequences and three classes of euchromatic sequences: X-transposed, X-degenerate and ampliconic. These classes contain all 156 known transcription units, which include 78 protein-coding genes that collectively encode 27 distinct proteins. The X-transposed sequences exhibit 99% identity to the X chromosome. The X-degenerate sequences are remnants of ancient autosomes from which the modern X and Y chromosomes evolved. The ampliconic class includes large regions (about 30% of the MSY euchromatin) where sequence pairs show greater than 99.9% identity, which is maintained by frequent gene conversion (non-reciprocal transfer). The most prominent features here are eight massive palindromes, at least six of which contain testis genes.

Initial sequencing and comparative analysis of the mouse genome.

RH Waterston — 2004-11-22T00:17:30-00:00

Nature, Vol. 420, No. 6915. (5 December 2002), pp. 520-562.

The sequence of the mouse genome is a key informational tool for understanding the contents of the human genome and a key experimental tool for biomedical research. Here, we report the results of an international collaboration to produce a high-quality draft sequence of the mouse genome. We also present an initial comparative analysis of the mouse and human genomes, describing some of the insights that can be gleaned from the two sequences. We discuss topics including the analysis of the evolutionary forces shaping the size, structure and sequence of the genomes; the conservation of large-scale synteny across most of the genomes; the much lower extent of sequence orthology covering less than half of the genomes; the proportions of the genomes under selection; the number of protein-coding genes; the expansion of gene families related to reproduction and immunity; the evolution of proteins; and the identification of intraspecies polymorphism.

Laser-driven proton scaling laws and new paths towards energy increase

J Fuchs — 2008-04-29T13:21:17-00:00

Nat Phys, Vol. 2, No. 1. (January 2006), pp. 48-54.

The past few years have seen remarkable progress in the development of laser-based particle accelerators. The ability to produce ultrabright beams of multi-megaelectronvolt protons routinely has many potential uses from engineering to medicine, but for this potential to be realized substantial improvements in the performances of these devices must be made. Here we show that in the laser-driven accelerator that has been demonstrated experimentally to produce the highest energy protons, scaling laws derived from fluid models and supported by numerical simulations can be used to accurately describe the acceleration of proton beams for a large range of laser and target parameters. This enables us to evaluate the laser parameters needed to produce high-energy and high-quality proton beams of interest for radiography of dense objects or proton therapy of deep-seated tumours.

Evolutionary and Biomedical Insights from the Rhesus Macaque Genome

Rhesus — 2007-04-13T05:22:30-00:00

Science, Vol. 316, No. 5822. (13 April 2007), pp. 222-234.

The rhesus macaque (Macaca mulatta) is an abundant primate species that diverged from the ancestors of Homo sapiens about 25 million years ago. Because they are genetically and physiologically similar to humans, rhesus monkeys are the most widely used nonhuman primate in basic and applied biomedical research. We determined the genome sequence of an Indian-origin Macaca mulatta female and compared the data with chimpanzees and humans to reveal the structure of ancestral primate genomes and to identify evidence for positive selection and lineage-specific expansions and contractions of gene families. A comparison of sequences from individual animals was used to investigate their underlying genetic diversity. The complete description of the macaque genome blueprint enhances the utility of this animal model for biomedical research and improves our understanding of the basic biology of the species. 10.1126/science.1139247

Assessment of reflective separator films for small crystal arrays

CM Pepin — 2008-03-14T15:45:20-00:00

Nuclear Science Symposium Conference Record, 2001 IEEE, Vol. 2 (2001), pp. 879-883 vol.2.

Thin, highly reflective, opaque separators are required to assemble compact arrays of small discrete scintillation crystals used in conjunction with photodiode array readouts in high-resolution imaging applications. Mechanical stability, individual detector performance, and ease of handling for wrapping crystals are the main factors to be considered in the choice of a suitable separator. Three different types of reflective materials were tested with 4/spl times/4 arrays of LSO, BGO and GSO: Tyvek 1058D paper, Toray Lumirror E60L Polyester Film, and 3M VM2000 Radiant Light Film. The light output and intrinsic energy resolution of individual crystals were measured as a function of their position in the arrays and the results were compared to simulation of light collection efficiency obtained with DETECT97. Optical crosstalk between adjacent and diagonal pixels was evaluated. The Lumirror film consistently yielded superior results with BGO. With LSO and GSO, the 3M reflector was found to provide slightly better light output and energy resolution. Despite the sharp cutoff in spectral reflectivity at 400 nm with this reflector, the crosstalk between adjacent LSO crystals was not found to be significant.

Properties of LYSO and recent LSO scintillators for phoswich PET detectors

CM Pepin — 2008-04-02T11:07:46-00:00

Nuclear Science, IEEE Transactions on, Vol. 51, No. 3. (2004), pp. 789-795.

The luminescence and nuclear spectroscopic properties of the new cerium-doped rare-earth scintillator lutetium-yttrium oxyorthosilicate (Lu/sub 0.6/Y/sub 1.4/Si/sub 0.5/:Ce, LYSO) were investigated and compared to those of both recent and older LSO crystals. UV-excited luminescent spectra outline important similarities between LYSO and LSO scintillators. The two distinct Ce1 and Ce2 luminescence mechanisms previously identified in LSO are also present in LYSO scintillators. The energy and timing resolutions were measured using avalanche photodiode (APD) and photomultiplier tube (PMT) readouts. The dependence of energy resolution on gamma-ray energy was also assessed to unveil the crystal intrinsic resolution parameters. In spite of significant progress in light output and luminescence properties, the energy resolution of these scintillators appears to still suffer from an excess variance in the number of scintillation photons. Pulse-shape discrimination between LYSO and LSO scintillators has been successfully achieved in phoswich assemblies, confirming LYSO, with a sufficient amount of yttrium to modify the decay time, to be a potential candidate for depth-of-interaction determination in multicrystal PET detectors.

Digital signal processing applied to crystal identification in Positron Emission Tomography dedicated to small animals

Rejean Fontaine — 2008-03-14T16:45:57-00:00

Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment, Vol. 571, No. 1-2. (1 February 2007), pp. 385-388.

The recent introduction of all-digital electronic architecture in Positron Emission Tomography (PET) scanners, enables new paradigms to be explored for extracting relevant information from the detector signals, such as energy, time and crystal identification. The LabPET(TM) small animal scanner, which implements free-running 45-MHz sampling directly at the output of the charge sensitive preamplifiers, provides an excellent platform to test such advanced digital algorithms. A real-time identification method, based on an Auto-Regressive Moving-Average (ARMA) scheme, was tested for discriminating between LYSO (tr~40 ns) and LGSO (tr~65 ns) scintillators in phoswich detectors, coupled to a single Avalanche Photodiode (APD). Even with a low energy threshold of 250 keV applied individually, error rates<4% can be achieved, as compared to >10%, typically with conventional analog pulse shape discrimination techniques. Such digital crystal identification techniques can be readily implemented with phoswich detectors for improving spatial resolution in PET, either by increasing crystal pixellization or by mitigating parallax errors through depth-of-interaction determination. It also allows to reduce the event rate presented to the real-time coincidence engine by applying a low energy limit at the crystal granularity and rejecting more Compton photons.

Asymmetric competitive suppression between strains of dengue virus

Kim Pepin — 2008-02-09T13:19:50-00:00

BMC Microbiology, Vol. 8 (08 February 2008), 28.

Extreme-ultraviolet Mo/Si multilayer mirrors deposited by radio-frequency-magnetron sputtering

Claude Montcalm — 2008-01-16T19:51:14-00:00

Appl. Opt., Vol. 33, No. 10. (1 April 1994), 2057.

Oxygen toxicity: simultaneous measure of pentane and malondialdehyde in humans exposed to hyperoxia.

MN Loiseaux-Meunier — 2007-12-06T11:30:51-00:00

Biomed Pharmacother, Vol. 55, No. 3. (April 2001), pp. 163-169.

In order to estimate cell damage caused by free radicals during oxygenotherapy, we investigated the time course of two markers of lipoperoxidation: pentane in breath and malondialdehyde (MDA) in blood during brief normobaric hyperoxia. Nine healthy subjects inhaled hydrocarbon-free air (HCFA) for 30 minutes, hydrocarbon-free 100% O2 (HCFO2) for 125 minutes and then HCFA for 70 minutes. After 15 minutes of washout with HCFA, ambient pentane was eliminated. After HCFO2, at T175 versus T30 (i.e., 145 min from the start of 100% HCFO2), pentane production increased (P< 0.05). MDA rose significantly at T155 min (i.e., 125 min from the start of HCFO2), versus T30 (P< 0.01). These results suggest that acute hyperoxia causes a moderate increase in lipid peroxidation in healthy subjects. The increase of pentane and MDA confirms that acute hyperoxia induces lipid peroxidation in healthy subjects.

Homogenization of regional river dynamics by dams and global biodiversity implications

Leroy Poff — 2007-12-02T01:28:26-00:00

Proceedings of the National Academy of Sciences, Vol. 104, No. 14. (3 April 2007), pp. 5732-5737.

Global biodiversity in river and riparian ecosystems is generated and maintained by geographic variation in stream processes and fluvial disturbance regimes, which largely reflect regional differences in climate and geology. Extensive construction of dams by humans has greatly dampened the seasonal and interannual streamflow variability of rivers, thereby altering natural dynamics in ecologically important flows on continental to global scales. The cumulative effects of modification to regional-scale environmental templates caused by dams is largely unexplored but of critical conservation importance. Here, we use 186 long-term streamflow records on intermediate-sized rivers across the continental United States to show that dams have homogenized the flow regimes on third- through seventh-order rivers in 16 historically distinctive hydrologic regions over the course of the 20th century. This regional homogenization occurs chiefly through modification of the magnitude and timing of ecologically critical high and low flows. For 317 undammed reference rivers, no evidence for homogenization was found, despite documented changes in regional precipitation over this period. With an estimated average density of one dam every 48 km of third- through seventh-order river channel in the United States, dams arguably have a continental scale effect of homogenizing regionally distinct environmental templates, thereby creating conditions that favor the spread of cosmopolitan, nonindigenous species at the expense of locally adapted native biota. Quantitative analyses such as ours provide the basis for conservation and management actions aimed at restoring and maintaining native biodiversity and ecosystem function and resilience for regionally distinct ecosystems at continental to global scales. 10.1073/pnas.0609812104

BIAS: Bioinformatics Integrated Application Software.

G Finak — 2006-11-06T19:44:46-00:00

Bioinformatics, Vol. 21, No. 8. (15 April 2005), pp. 1745-1746.

MOTIVATION: We introduce a development platform especially tailored to Bioinformatics research and software development. BIAS (Bioinformatics Integrated Application Software) provides the tools necessary for carrying out integrative Bioinformatics research requiring multiple datasets and analysis tools. It follows an object-relational strategy for providing persistent objects, allows third-party tools to be easily incorporated within the system and supports standards and data-exchange protocols common to Bioinformatics. AVAILABILITY: BIAS is an OpenSource project and is freely available to all interested users at http://www.mcb.mcgill.ca/~bias/. This website also contains a paper containing a more detailed description of BIAS and a sample implementation of a Bayesian network approach for the simultaneous prediction of gene regulation events and of mRNA expression from combinations of gene regulation events. CONTACT: hallett@mcb.mcgill.ca.

An examination of the differences between surface and free-air temperature trend at high-elevation sites: Relationships with cloud cover, snow cover, and wind

NC Pepin — 2007-09-04T15:01:08-00:00

Journal of Geophysical Research, Vol. 110 (24 December 2005), D24112.

Predicting the vertical profiles of anchovy (Engraulis mordax) and sardine (Sardinops sagax) eggs in the California Current System

Alexandra Curtis — 2006-12-15T22:02:47-00:00

Fisheries Oceanography, Vol. 16, No. 1. (January 2007), pp. 68-84.

Social Support: A Mediator between Child Maltreatment and Developmental Outcomes

Elise Pepin — 2007-07-07T16:56:04-00:00

Journal of Youth and Adolescence, Vol. 35, No. 4. (2006), pp. 612-625.

The purpose of the current study was to investigate the relationship between child maltreatment, social support, and developmental outcomes in first-year college students. Participants were 202 undergraduate students (137 female, 65 male) who completed surveys at two time points: once before entering college and once during their first year of college. It was hypothesized that child maltreatment would predict poorer developmental outcomes in adolescence and early adulthood, but that social support would mediate this relationship. Results indicated that child maltreatment related negatively to developmental outcomes and to perceived social support; adolescent and young adult development related positively to perceived social support. In addition, a mediational model in which social support mediates child maltreatment and developmental outcomes was supported.

Gene expression signatures of morphologically normal breast tissue identify basal-like tumors

Greg Finak — 2006-10-20T22:16:30-00:00

Breast Cancer Research, Vol. 8 (20 October 2006), R58.

Sleep apnea in the elderly: A specific entity?

Sandrine Launois — 2007-03-05T01:11:15-00:00

Sleep Medicine Reviews, Vol. 11, No. 2. (April 2007), pp. 87-97.

Summary Sleep apnea is highly prevalent in subjects after age 60, and affects older men and women similarly. Central apneas are often observed in addition to obstructive and mixed events. Pathogenesis of obstructive and central events during sleep in the elderly can be attributed to an amplification of well-established causes of sleep-disordered breathing (SDB) in younger adults. As in middle-aged adults, sleep-related complaints, cardiovascular diseases, depression and traffic accidents should prompt an evaluation by a sleep specialist. However, secondary enuresis and nocturia, cognitive impairment, ophthalmic conditions and repeated falls may be the main complaint in elderly subjects. Sleep studies in the elderly should systematically include reliable means to detect central apneas and periodic leg movements. Untreated SDB in the elderly appears to have a lesser impact on mortality than in middle-aged adults. However, the typical morbidity associated with the disorder in younger adults is observed in the elderly. Elderly symptomatic SDB patients tolerate CPAP no differently than younger patients and should be effectively treated. In conclusion, whether sleep apnea in the elderly represents a specific entity or the same disease as in younger subjects, with some distinctive features, is still unclear. Further research, in particular focusing on the impact of age on SDB outcomes, is needed.

Exploring the high sensitivity of SU-8 resist for high resolution electron beam patterning

A Pepin — 2006-07-27T07:46:54-00:00

Microelectronic Engineering, Vol. 73-74 (June 2004), pp. 233-237.

We have explored the feasibility of using negative epoxy novolak-based SU-8 2002 resist as an electron beam lithography resist for ultra high speed fabrication of large areas of high resolution patterns. 75 nm-wide lines have been obtained in thin-layered SU-8 films, using a 50 keV electron beam system, and the required exposure dose was found to be around 3.6 [mu]C/cm2, which is more than 100 times less than that of commonly used polymethyl methacrylate resist (typically 500 [mu]C/cm2). Therefore, mass production of large areas of nanostructures should be possible for a number of applications.

Variable Pleiotropic Effects From Mutations at the Same Locus Hamper Prediction of Fitness From a Fitness Component

Kim Pepin — 2006-04-24T19:34:39-00:00

Genetics, Vol. 172, No. 4. (1 April 2006), pp. 2047-2056.

The relationship of genotype, fitness components, and fitness can be complicated by genetic effects such as pleiotropy and epistasis and by heterogeneous environments. However, because it is often difficult to measure genotype and fitness directly, fitness components are commonly used to estimate fitness without regard to genetic architecture. The small bacteriophage phiX174 enables direct evaluation of genetic and environmental effects on fitness components and fitness. We used 15 mutants to study mutation effects on attachment rate and fitness in six hosts. The mutants differed from our lab strain of phiX174 by only one or two amino acids in the major capsid protein (gpF, sites 101 and 102). The sites are variable in natural and experimentally evolved phiX174 populations and affect phage attachment rate. Within the limits of detection of our assays, all mutations were neutral or deleterious relative to the wild type; 11 mutants had decreased host range. While fitness was predictable from attachment rate in most cases, 3 mutants had rapid attachment but low fitness on most hosts. Thus, some mutations had a pleiotropic effect on a fitness component other than attachment rate. In addition, on one host most mutants had high attachment rate but decreased fitness, suggesting that pleiotropic effects also depended on host. The data highlight that even in this simple, well-characterized system, prediction of fitness from a fitness component depends on genetic architecture and environment. 10.1534/genetics.105.049817

Electron beam lithography: resolution limits and applications

C Vieu — 2006-02-22T21:03:33-00:00

Applied Surface Science, Vol. 164, No. 1-4. (1 September 2000), pp. 111-117.

We report on the resolution limits of Electron Beam Lithography (EBL) in the conventional polymethylmethacrylate (PMMA) organic resist. We show that resolution can be pushed below 10 nm for isolated features and how dense arrays of periodic structures can be fabricated at a pitch of 30 nm, leading to a density close to 700 Gbit/in2. We show that intrinsic resolution of the writing in the resist is as small as 3 to 5 nm at high incident electron energy, and that practical resolution is limited by the development of the resist after exposure and by pattern transfer. We present the results of our optimized process for reproducible fabrication of sub-10 nm lines by lift-off and 30-nm pitch pillar arrays by lift-off and reactive ion etching (RIE). We also present some applications of these nanostructures for the fabrication of very high density molds for nano-imprint lithography (NIL) and for the fabrication of Multiple Tunnel Junction devices that can be used for single electron device applications or for the connection of small molecules.

Identifying regulatory subnetworks for a set of genes.

MS Scott — 2005-11-15T05:35:29-00:00

Mol Cell Proteomics, Vol. 4, No. 5. (May 2005), pp. 683-692.

High throughput genomic/proteomic strategies, such as microarray studies, drug screens, and genetic screens, often produce a list of genes that are believed to be important for one or more reasons. Unfortunately it is often difficult to discern meaningful biological relationships from such lists. This study presents a new bioinformatic approach that can be used to identify regulatory subnetworks for lists of significant genes or proteins. We demonstrate the utility of this approach using an interaction network for yeast constructed from BIND, TRANSFAC, SCPD, and chromatin immunoprecipitation (ChIP)-Chip data bases and lists of genes from well known metabolic pathways or differential expression experiments. The approach accurately rediscovers known regulatory elements of the heat shock response as well as the gluconeogenesis, galactose, glycolysis, and glucose fermentation pathways in yeast. We also find evidence supporting a previous conjecture that approximately half of the enzymes in a metabolic pathway are transcriptionally co-regulated. Finally we demonstrate a previously unknown connection between GAL80 and the diauxic shift in yeast.