2,262 research outputs found
Bidirectional crosstalk between hypoxia-inducible factor and glucocorticoid signalling in zebrafish larvae
In the last decades in vitro studies highlighted the potential for crosstalk between Hypoxia-Inducible Factor-(HIF) and glucocorticoid-(GC) signalling pathways. However, how this interplay precisely occurs in vivo is still debated. Here, we use zebrafish larvae (Danio rerio) to elucidate how and to what degree hypoxic signalling affects the endogenous glucocorticoid pathway and vice versa, in vivo. Firstly, our results demonstrate that in the presence of upregulated HIF signalling, both glucocorticoid receptor (Gr) responsiveness and endogenous cortisol levels are repressed in 5 days post fertilisation larvae. In addition, despite HIF activity being low at normoxia, our data show that it already impedes both glucocorticoid activity and levels. Secondly, we further analysed the in vivo contribution of glucocorticoids to HIF activity. Interestingly, our results show that both glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) play a key role in enhancing it. Finally, we found indications that glucocorticoids promote HIF signalling via multiple routes. Cumulatively, our findings allowed us to suggest a model for how this crosstalk occurs in vivo
Individual leader to interdependent leadership: A case study in leadership development and tripartite evaluation
This article is available open access through the publisher’s website at the link below. Copyright @ 2013 Sage Publications.The Problem - In this case study we see a move away from orthodox views of school leadership as “headship” to a more contemporary model of educational leadership wherein we note a departure from functional, curricula-based school leadership toward more human resource development (HRD) approaches. The aim of this study was to consider the effectiveness of an educational development program for middle leaders within an educational establishment.
The Solution - We examined the impact of a bespoke higher education leadership development intervention in Leadership (and Change) on the formation and cohesiveness of a newly formed innovative leadership structure.
The Stakeholders - The leadership development intervention was designed through a tripartite collaboration including a university, senior school leaders, and staff. The intervention was designed to shift leadership from individual leader agency to interdependent human leadership agency. Through tripartite evaluation we uncover leadership development praxis that transcends the boundaries of conventional educational leadership and reemphasizes the benefits of bridging the academic/practitioner divide and the application of theory to praxis
Responsible management: Engaging moral reflexive practice through threshold concepts
YesIn this conceptual paper we argue that, to date, principles of responsible management have not impacted practice as anticipated because of a disconnect between knowledge and practice. This disconnect means that an awareness of ethical concerns, by itself, does not help students take personal responsibility for their actions. We suggest that an abstract knowledge of principles has to be supplemented by an engaged understanding of the responsibility of managers and leaders to actively challenge irresponsible practices. We argue that a form of moral reflexive practice drawing on an understanding of threshold concepts is central to responsible management, and provides a gateway to transformative learning. Our conceptual argument leads to implications for management and professional education
Measurement of the Branching Fraction of the Decay in Fully Reconstructed Events at Belle
We present an analysis of the exclusive
decay, where represents an
electron or a muon, with the assumption of charge-conjugation symmetry and
lepton universality. The analysis uses the full data sample
collected by the Belle detector, corresponding to 711 fb of integrated
luminosity. We select the events by fully reconstructing one meson in
hadronic decay modes, subsequently determining the properties of the other
meson. We extract the signal yields using a binned maximum-likelihood fit to
the missing-mass squared distribution in bins of the invariant mass of the two
pions or the momentum transfer squared. We measure a total branching fraction
of , where the
uncertainties are statistical and systematic, respectively. This result is the
first reported measurement of this decay.Comment: 23 pages, 19 figure
Inclusive study of bottomonium production in association with an meson in annihilations near
We study bottomonium production in association with an meson in
annihilations near the , at a center of mass energy of
GeV. The results are based on the fb data
sample collected by the Belle experiment at the asymmetric energy KEKB
collider. Only the meson is reconstructed and the missing-mass spectrum
of candidates is investigated. We observe the
process and find evidence for the
process, while no significant signals of
, , nor are found. Cross sections for the
studied processes are reported.Comment: Submitted to EPJ-
The epigenetic regulator Histone Deacetylase 1 promotes transcription of a core neurogenic programme in zebrafish embryos
<p>Abstract</p> <p>Background</p> <p>The epigenetic regulator Histone Deacetylase 1 (Hdac1) is required for specification and patterning of neurones and myelinating glia during development of the vertebrate central nervous system (CNS). This co-ordinating function for Hdac1 is evolutionarily conserved in zebrafish and mouse, but the mechanism of action of Hdac1 in the developing CNS is not well-understood.</p> <p>Results</p> <p>A genome-wide comparative analysis of the transcriptomes of Hdac1-deficient and wild-type zebrafish embryos was performed, which identified an extensive programme of gene expression that is regulated by Hdac1 in the developing embryo. Using time-resolved expression profiling of embryos, we then identified a small subset of 54 genes within the Hdac1-regulated transcriptome that specifically exhibit robust and sustained Hdac1-dependent expression from early neurogenesis onwards. 18 of these 54 stringently Hdac1-regulated genes encode DNA-binding transcription factors that are implicated in promoting neuronal specification and CNS patterning, including the proneural bHLH proteins Ascl1a and Ascl1b, as well as Neurod4 and Neurod. Relatively few genes are strongly repressed by Hdac1 but expression of the Notch target gene <it>her6 </it>is attenuated by Hdac1 in specific sub-regions of the developing CNS, from early stages of neurogenesis onwards. Selected members of the stringently Hdac1-regulated group of genes were tested for Hdac1 binding to their promoter-proximal <it>cis</it>-regulatory elements. Surprisingly, we found that Hdac1 is specifically and stably associated with DNA sequences within the promoter region of <it>ascl1b </it>during neurogenesis, and that this Hdac1-<it>ascl1b </it>interaction is abolished in <it>hdac1 </it>mutant embryos.</p> <p>Conclusions</p> <p>We conclude that Hdac1 regulates histone acetylation and methylation in the developing zebrafish embryo and promotes the sustained, co-ordinate transcription of a small set of transcription factor genes that control expansion and diversification of cell fates within the developing CNS. Our <it>in vivo </it>chromatin immunoprecipitation results also suggest a specific function for Hdac1 in directly regulating transcription of a key member of this group of genes, <it>ascl1b</it>, from the beginning of neurogenesis onwards. Taken together, our observations indicate a novel role for Hdac1 as a positive regulator of gene transcription during development of the vertebrate CNS, in addition to its more well-established function in transcriptional repression.</p
Measurement of the CKM Matrix Element from at Belle
We present a new measurement of the CKM matrix element from decays, reconstructed with the full Belle data set
of integrated luminosity. Two form factor
parameterizations, originally conceived by the Caprini-Lellouch-Neubert (CLN)
and the Boyd, Grinstein and Lebed (BGL) groups, are used to extract the product
and the decay form factors, where
is the normalization factor and is a small
electroweak correction. In the CLN parameterization we find
, , , . For the BGL parameterization we
obtain , which is consistent with the World Average when correcting for
. The branching fraction of is measured to be . We also present a new
test of lepton flavor universality violation in semileptonic decays,
. The errors correspond to the statistical and
systematic uncertainties respectively. This is the most precise measurement of
and form factors to date and the first
experimental study of the BGL form factor parameterization in an experimental
measurement
CsI(Tl) Pulse Shape Discrimination with the Belle II Electromagnetic Calorimeter as a Novel Method to Improve Particle Identification at Electron-Positron Colliders
This paper describes the implementation and performance of CsI(Tl) pulse
shape discrimination for the Belle II electromagnetic calorimeter, representing
the first application of CsI(Tl) pulse shape discrimination for particle
identification at an electron-positron collider. The pulse shape
characterization algorithms applied by the Belle II calorimeter are described.
Control samples of , , , and are
used to demonstrate the significant insight into the secondary particle
composition of calorimeter clusters that is provided by CsI(Tl) pulse shape
discrimination. Comparisons with simulation are presented and provide further
validation for newly developed CsI(Tl) scintillation response simulation
techniques, which when incorporated with GEANT4 simulations allow the particle
dependent scintillation response of CsI(Tl) to be modelled. Comparisons between
data and simulation also demonstrate that pulse shape discrimination can be a
new tool to identify sources of improvement in the simulation of hadronic
interactions in materials. The efficiency and photon-as-hadron
fake-rate of a multivariate classifier that is trained to use pulse shape
discrimination is presented and comparisons are made to a shower-shape based
approach. CsI(Tl) pulse shape discrimination is shown to reduce the
photon-as-hadron fake-rate by over a factor of 3 at photon energies of 0.2 GeV
and over a factor 10 at photon energies of 1 GeV
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