165 research outputs found
Professorial Hegemony Unveiled: Opportunities and Challenges in Building a Career in IS
Information Systems (IS) academics who have recently achieved professorial status often confess that their promotion process has been long, sometimes painful, occasionally unfair, and almost invariably political. Also, it is clear that the perceptions about promotion criteria vary across schools, countries and continents. This situation is particularly worrying for ‘mid career’ academics, i.e., colleagues who are neither junior nor senior, but aspire to a professorial appointment. In response to this concern, this panel brings together professors from both sides of the Atlantic, who will expose this diversity in the practices, opportunities and pitfalls in the promotion process, reflecting on their own experience, but also shaping a debate on what makes a successful academic career in information systems. The panel is an opportunity for the IS community to reflect on current practices, defend or challenge them and discuss lessons that can be learned for the future
In Vivo Expression of MHC Class I Genes Depends on the Presence of a Downstream Barrier Element
Regulation of MHC class I gene expression is critical to achieve proper immune surveillance. In this work, we identify elements downstream of the MHC class I promoter that are necessary for appropriate in vivo regulation: a novel barrier element that protects the MHC class I gene from silencing and elements within the first two introns that contribute to tissue specific transcription. The barrier element is located in intergenic sequences 3′ to the polyA addition site. It is necessary for stable expression in vivo, but has no effect in transient transfection assays. Accordingly, in both transgenic mice and stably transfected cell lines, truncation of the barrier resulted in transcriptional gene silencing, increased nucleosomal density and decreased histone H3K9/K14 acetylation and H3K4 di-methylation across the gene. Significantly, distinct sequences within the barrier element govern anti-silencing and chromatin modifications. Thus, this novel barrier element functions to maintain transcriptionally permissive chromatin organization and prevent transcriptional silencing of the MHC class I gene, ensuring it is poised to respond to immune signaling
Three Novel Downstream Promoter Elements Regulate MHC Class I Promoter Activity in Mammalian Cells
BACKGROUND: MHC CLASS I TRANSCRIPTION IS REGULATED BY TWO DISTINCT TYPES OF REGULATORY PATHWAYS: 1) tissue-specific pathways that establish constitutive levels of expression within a given tissue and 2) dynamically modulated pathways that increase or decrease expression within that tissue in response to hormonal or cytokine mediated stimuli. These sets of pathways target distinct upstream regulatory elements, have distinct basal transcription factor requirements, and utilize discrete sets of transcription start sites within an extended core promoter. METHODOLOGY/PRINCIPAL FINDINGS: We studied regulatory elements within the MHC class I promoter by cellular transfection and in vitro transcription assays in HeLa, HeLa/CIITA, and tsBN462 of various promoter constructs. We have identified three novel MHC class I regulatory elements (GLE, DPE-L1 and DPE-L2), located downstream of the major transcription start sites, that contribute to the regulation of both constitutive and activated MHC class I expression. These elements located at the 3' end of the core promoter preferentially regulate the multiple transcription start sites clustered at the 5' end of the core promoter. CONCLUSIONS/SIGNIFICANCE: Three novel downstream elements (GLE, DPE-L1, DPE-L2), located between +1 and +32 bp, regulate both constitutive and activated MHC class I gene expression by selectively increasing usage of transcription start sites clustered at the 5' end of the core promoter upstream of +1 bp. Results indicate that the downstream elements preferentially regulate TAF1-dependent, relative to TAF1-independent, transcription
A Study of Muon Neutrino Disappearance Using the Fermilab Main Injector Neutrino Beam
We report the results of a search for muon-neutrino disappearance by the Main
Injector Neutrino Oscillation Search. The experiment uses two detectors
separated by 734 km to observe a beam of neutrinos created by the Neutrinos at
the Main Injector facility at Fermi National Accelerator Laboratory. The data
were collected in the first 282 days of beam operations and correspond to an
exposure of 1.27e20 protons on target. Based on measurements in the Near
Detector, in the absence of neutrino oscillations we expected 336 +/- 14
muon-neutrino charged-current interactions at the Far Detector but observed
215. This deficit of events corresponds to a significance of 5.2 standard
deviations. The deficit is energy dependent and is consistent with two-flavor
neutrino oscillations according to delta m-squared = 2.74e-3 +0.44/-0.26e-3
eV^2 and sin^2(2 theta) > 0.87 at 68% confidence level.Comment: In submission to Phys. Rev.
Measurement of neutrino velocity with the MINOS detectors and NuMI neutrino beam
The velocity of a ~3 GeV neutrino beam is measured by comparing detection times at the near and far detectors of the MINOS experiment, separated by 734 km. A total of 473 far detector neutrino events was used to measure (v-c)/c=5.12.910-5 (at 68% C.L.). By correlating the measured energies of 258 charged-current neutrino events to their arrival times at the far detector, a limit is imposed on the neutrino mass of mnu<50 MeV/c2 (99% C.L.)
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Search for the disappearance of muon antineutrinos in the NuMI neutrino beam
We report constraints on antineutrino oscillation parameters that were obtained by using the two MINOS detectors to measure the 7% muon antineutrino component of the NuMI neutrino beam. In the Far Detector, we select 130 events in the charged-current muon antineutrino sample, compared to a prediction of 136.4 ± 11.7(stat)^(+10.2)_(-8.9)(syst) events under the assumption │Δm^2│ = 2.32 X 10^(-3) eV^2, sin^2(2θ) = 1.0
Measurement of the Atmospheric Muon Charge Ratio at TeV Energies with MINOS
The 5.4 kton MINOS far detector has been taking charge-separated cosmic ray
muon data since the beginning of August, 2003 at a depth of 2070
meters-water-equivalent in the Soudan Underground Laboratory, Minnesota, USA.
The data with both forward and reversed magnetic field running configurations
were combined to minimize systematic errors in the determination of the
underground muon charge ratio. When averaged, two independent analyses find the
charge ratio underground to be 1.374 +/- 0.004 (stat.) +0.012 -0.010(sys.).
Using the map of the Soudan rock overburden, the muon momenta as measured
underground were projected to the corresponding values at the surface in the
energy range 1-7 TeV. Within this range of energies at the surface, the MINOS
data are consistent with the charge ratio being energy independent at the two
standard deviation level. When the MINOS results are compared with measurements
at lower energies, a clear rise in the charge ratio in the energy range 0.3 --
1.0 TeV is apparent. A qualitative model shows that the rise is consistent with
an increasing contribution of kaon decays to the muon charge ratio.Comment: 16 pages, 17 figure
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First Direct Observation of Muon Antineutrino Disappearance
This Letter reports the first direct observation of muon antineutrino disappearance. The MINOS experiment has taken data with an accelerator beam optimized for ν̅ _μ production, accumulating an exposure of 1.71×10^(20) protons on target. In the Far Detector, 97 charged current ν̅ _μ events are observed. The no-oscillation hypothesis predicts 156 events and is excluded at 6.3σ. The best fit to oscillation yields |Δm̅ 2|= [3.36=_(-0.40)^(+0.46)(stat)±0.06(syst)]x10^(-3)eV^2,sin^2(2θ̅)=0.86 _(-0.12)^(+0.11)(stat)±0.01(syst). The MINOS ν̅ _μ and ν̅ _μ measurements are consistent at the 2.0% confidence level, assuming identical underlying oscillation parameters
First observations of separated atmospheric nu_mu and bar{nu-mu} events in the MINOS detector
The complete 5.4 kton MINOS far detector has been taking data since the beginning of August 2003 at a depth of 2070 meters water-equivalent in the Soudan mine, Minnesota. This paper presents the first MINOS observations of nuµ and [overline nu ]µ charged-current atmospheric neutrino interactions based on an exposure of 418 days. The ratio of upward- to downward-going events in the data is compared to the Monte Carlo expectation in the absence of neutrino oscillations, giving Rup/downdata/Rup/downMC=0.62-0.14+0.19(stat.)±0.02(sys.). An extended maximum likelihood analysis of the observed L/E distributions excludes the null hypothesis of no neutrino oscillations at the 98% confidence level. Using the curvature of the observed muons in the 1.3 T MINOS magnetic field nuµ and [overline nu ]µ interactions are separated. The ratio of [overline nu ]µ to nuµ events in the data is compared to the Monte Carlo expectation assuming neutrinos and antineutrinos oscillate in the same manner, giving R[overline nu ][sub mu]/nu[sub mu]data/R[overline nu ][sub mu]/nu[sub mu]MC=0.96-0.27+0.38(stat.)±0.15(sys.), where the errors are the statistical and systematic uncertainties. Although the statistics are limited, this is the first direct observation of atmospheric neutrino interactions separately for nuµ and [overline nu ]µ
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