998 research outputs found
La dynamique de transformation de la direction des systeÌmes dâinformation
Les directions des systeÌmes dâinformation (DSI) se sont consideÌrablement transformeÌes depuis leur apparition dans les organisations. Pourtant, peu de chercheurs ont tenteÌ de mieux comprendre le processus de transformation des DSI. Cet article a donc pour objectif dâexplorer la question suivante : comment et pourquoi les DSI se transforment-elles au sein des organisations ? Afin dâeÌtudier cette question, nous avons deÌveloppeÌ un cadre concep- tuel dâanalyse construit autour dâune typologie des DSI qui sâappuie eÌgalement sur la theÌorie des eÌquilibres ponctueÌs. Deux eÌtudes de cas ont eÌteÌ meneÌes dans des entreprises provenant de secteurs dâaffaires diffeÌrents. Nos reÌsultats suggeÌrent que les DSI se transforment en reÌaction aÌ des forces secondaires qui les poussent vers le changement, mais uniquement lorsque ces forces secondaires agissent sur elles par lâintermeÌdiaire de trois forces primaires, soient : 1) la vision de lâorganisation quant au potentiel des outils technologiques, 2) la participation du chef de lâinformation (CI) aÌ la prise de deÌcision strateÌgique et 3) le niveau de connaissance en systeÌmes dâinformation des membres de la haute direction. Lorsque les forces secondaires nâaffectent pas les forces primaires, une DSI conserve son profil ideÌal existant. Cette eÌtude vient combler un vide important dans la litteÌrature en systeÌmes dâinformation en proposant une theÌorie explicative de la dynamique de transformation de la DSI dans les organisations
Novel Association of HK1 with Glycated Hemoglobin in a Non-Diabetic Population: A Genome-Wide Evaluation of 14,618 Participants in the Women's Genome Health Study
Type 2 diabetes is a leading cause of morbidity and mortality. While genetic variants have been found to influence the risk of type 2 diabetes mellitus, relatively few studies have focused on genes associated with glycated hemoglobin, an index of the mean blood glucose concentration of the preceding 8â12 weeks. Epidemiologic studies and randomized clinical trials have documented the relationship between glycated hemoglobin levels and the development of long-term complications in diabetes; moreover, higher glycated hemoglobin levels in the subdiabetic range have been shown to predict type 2 diabetes risk and cardiovascular disease. To examine the common genetic determinants of glycated hemoglobin levels, we performed a genome-wide association study that evaluated 337,343 SNPs in 14,618 apparently healthy Caucasian women. The results show that glycated hemoglobin levels are associated with genetic variation at the GCK (rs730497; Pâ=â2.8Ă10â12), SLC30A8 (rs13266634; Pâ=â9.8Ă10â8), G6PC2 (rs1402837; Pâ=â6.8Ă10â10), and HK1 (rs7072268; Pâ=â6.4Ă10â9) loci. While associations at the GCK, SLC30A8, and G6PC2 loci are confirmatory, the findings at HK1 are novel. We were able to replicate this novel association in an independent validation sample of 455 additional non-diabetic men and women. HK1 encodes the enzyme hexokinase, the first step in glycolysis and a likely candidate for the control of glucose metabolism. This observed genetic association between glycated hemoglobin levels and HK1 polymorphisms paves the way for further studies of the role of HK1 in hemoglobin glycation, glucose metabolism, and diabetes
Multi-band Superconductivity in the Chevrel Phases SnMo6S8 and PbMo6S8
Sub-Kelvin scanning tunnelling spectroscopy in the Chevrel Phases SnMo6S8 and
PbMo6S8 reveals two distinct superconducting gaps with Delta_1 = 3 meV, Delta_2
~ 1.0 meV and Delta_1 = 3.1 meV, Delta_2 ~ 1.4 meV respectively. The gap
distribution is strongly anisotropic, with Delta_2 predominantly seen when
scanning across unit-cell steps on the (001) sample surface. The spectra are
well-fitted by an anisotropic two-band BCS s-wave gap function. Our
spectroscopic data are confirmed by electronic heat capacity measurements which
also provide evidence for a twin-gap scenario.Comment: 5 pages, 4 figure
Detection of subthreshold pulses in neurons with channel noise
Neurons are subject to various kinds of noise. In addition to synaptic noise,
the stochastic opening and closing of ion channels represents an intrinsic
source of noise that affects the signal processing properties of the neuron. In
this paper, we studied the response of a stochastic Hodgkin-Huxley neuron to
transient input subthreshold pulses. It was found that the average response
time decreases but variance increases as the amplitude of channel noise
increases. In the case of single pulse detection, we show that channel noise
enables one neuron to detect the subthreshold signals and an optimal membrane
area (or channel noise intensity) exists for a single neuron to achieve optimal
performance. However, the detection ability of a single neuron is limited by
large errors. Here, we test a simple neuronal network that can enhance the
pulse detecting abilities of neurons and find dozens of neurons can perfectly
detect subthreshold pulses. The phenomenon of intrinsic stochastic resonance is
also found both at the level of single neurons and at the level of networks. At
the network level, the detection ability of networks can be optimized for the
number of neurons comprising the network.Comment: 14 pages, 9 figure
The distribution and movement patterns of four woodland caribou herds in Quebec and Labrador
Recent studies of woodland caribou (Rangifer tarandus caribou) in northern Quebec and central Labrador have demonstrated similar patterns of seasonal movements and distribution among four herds. Aerial surveys and radio-telemetry indicated that animals occupied forest-wetland habitat at densities of 0.03 caribou km2, or lower, for most of the year. Although females were widely dispersed at calving individuals demonstrated fidelity toward specific calving locations, in successive years. Caribou did not form large post-calving aggregations. Movement was greatest in the spring, prior to calving, and in the fall, during or immediately after rutting. Caribou were generally sedentary during summer and winter, although some moved relatively long distances to late-winter range. Although the herds occupy continuous range across Quebec and Labrador, our data indicate that the herds are largely discreete and should be managed individually
Cannabis use and risk of schizophrenia: a Mendelian randomization study.
Cannabis use is observationally associated with an increased risk of schizophrenia, but whether the relationship is causal is not known. Using a genetic approach, we took 10 independent genetic variants previously identified to associate with cannabis use in 32 330 individuals to determine the nature of the association between cannabis use and risk of schizophrenia. Genetic variants were employed as instruments to recapitulate a randomized controlled trial involving two groups (cannabis users vs nonusers) to estimate the causal effect of cannabis use on risk of schizophrenia in 34 241 cases and 45 604 controls from predominantly European descent. Genetically-derived estimates were compared with a meta-analysis of observational studies reporting ever use of cannabis and risk of schizophrenia or related disorders. Based on the genetic approach, use of cannabis was associated with increased risk of schizophrenia (odds ratio (OR) of schizophrenia for users vs nonusers of cannabis: 1.37; 95% confidence interval (CI), 1.09-1.67; P-value=0.007). The corresponding estimate from observational analysis was 1.43 (95% CI, 1.19-1.67; P-value for heterogeneity =0.76). The genetic markers did not show evidence of pleiotropic effects and accounting for tobacco exposure did not alter the association (OR of schizophrenia for users vs nonusers of cannabis, adjusted for ever vs never smoker: 1.41; 95% CI, 1.09-1.83). This adds to the substantial evidence base that has previously identified cannabis use to associate with increased risk of schizophrenia, by suggesting that the relationship is causal. Such robust evidence may inform public health messages about cannabis use, especially regarding its potential mental health consequences
Immune infiltrate composition across intrinsic subtypes in hormone receptor (HR)+/HER2- early breast cancer (BC) enrolled in the prospective LETLOB trial.
Background
In HR+/HER2- early BC, high tumour infiltrating lymphocytes (TIL) levels predict higher pathological complete response to neoadjuvant chemotherapy, but are associated with shorter overall survival (Denkert, Lancet Oncol 2018). HR+/HER2- BC is a biologically heterogeneous disease, encompassing all BC molecular intrinsic subtypes, with different clinical behaviour (Cejalvo, CTR 2018). Little is known concerning the distribution of TIL levels and immune infiltrate composition across intrinsic subtypes in HR+/HER2- BC.
Methods
Gene-expression data (Affymetrix platform) from pre-treatment frozen core-biopsies was available from 66 postmenopausal patients with HR+/HER2- early BC from the LETLOB trial (neoadjuvant letrozole+/-lapatinib) (Guarneri, JCO 2014). Intrinsic subtype was assigned using a research-based PAM50 subtype predictor. Relative leukocyte fractions were calculated using CIBERSORT (Newman, Nature Methods 2015), a deconvolution method based on RNA gene-expression signatures. Pre-treatment stromal TILs were assessed on centralized HES slides according to recommendations (Salgado, Ann Oncol 2015).
Results
Intrinsic subtype distribution was as follows: basal 18% (Nâ=â12), HER2-enriched 8% (Nâ=â5), Luminal A 39% (Nâ=â25), Luminal B 36% (Nâ=â24). Non-luminal subtypes (HER2-enriched and Basal) had significantly higher baseline TIL levels than luminal subtypes (median (range): 7 (0-100) and 2 (0-35), respectively; pâ=â0.038). Non-luminal subtypes also presented higher fractions of CD4 memory activated T-cells (pâ=â0.018), γΎ T-cells (pâ=â0.010) and M1 macrophages (pâ=â0.001) and lower fractions of T-regulatory cells (pâ=â0.002) than luminal subtypes.
Conclusions
In HR+/HER2- early BC, non-luminal subtypes show higher TIL levels and a more pro-inflammatory anti-tumour immune infiltrate composition. This immune heterogeneity across intrinsic subtypes should be considered when analysing the complex prognostic role of TILs in HR+/HER2- early BC
Very High Energy Gamma-ray spectral properties of Mrk 501 from CAT Cerenkov telescope observations in 1997
The BL Lac object Mrk 501 went into a very high state of activity during
1997, both in VHE gamma-rays and X-rays. We present here results from
observations at energies above 250 GeV carried out between March and October
1997 with the CAT Cerenkov imaging Telescope. The average differential spectrum
between 30 GeV and 13 TeV shows significant curvature and is well represented
by phi_0 * E_TeV^{-(alpha + beta*log10(E_TeV))}, with: phi_0 = 5.19 +/- 0.13
{stat} +/- 0.12 {sys-MC} +1.66/-1.04 {sys-atm} * 10^-11 /cm^2/s/TeV alpha =
2.24 +/- 0.04 {stat} +/- 0.05 {sys} beta = 0.50 +/- 0.07 {stat} (negligible
systematics). The TeV spectral energy distribution of Mrk 501 clearly peaks in
the range 500 GeV-1 TeV. Investigation of spectral variations shows a
significant hardness-intensity correlation with no measurable effect on the
curvature. This can be described as an increase of the peak TeV emission energy
with intensity. Simultaneous and quasi-simultaneous CAT VHE gamma-ray and
BeppoSAX hard X-ray detections for the highest recorded flare on 16th April and
for lower-activity states of the same period show correlated variability with a
higher luminosity in X-rays than in gamma-rays. The observed spectral energy
distribution and the correlated variability between X-rays and gamma-rays, both
in amplitude and in hardening of spectra, favour a two-component emission
scheme where the low and high energy components are attributed to synchrotron
and inverse Compton (IC) radiation, respectively.Comment: Submitted to Astronomy and Astrophysics, 8 pages including 6 figures.
Published with minor change
The CAT Imaging Telescope for Very-High-Energy Gamma-Ray Astronomy
The CAT (Cherenkov Array at Themis) imaging telescope, equipped with a
very-high-definition camera (546 fast phototubes with 0.12 degrees spacing
surrounded by 54 larger tubes in two guard rings) started operation in Autumn
1996 on the site of the former solar plant Themis (France). Using the
atmospheric Cherenkov technique, it detects and identifies very high energy
gamma-rays in the range 250 GeV to a few tens of TeV. The instrument, which has
detected three sources (Crab nebula, Mrk 421 and Mrk 501), is described in
detail.Comment: 24 pages, 15 figures. submitted to Elsevier Preprin
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