2,038 research outputs found
A structured approach to the study of metabolic control principles in intact and impaired mitochondria.
We devised an approach to extract control principles of cellular bioenergetics for intact and impaired mitochondria from ODE-based models and applied it to a recently established bioenergetic model of cancer cells. The approach used two methods for varying ODE model parameters to determine those model components that, either alone or in combination with other components, most decisively regulated bioenergetic state variables. We found that, while polarisation of the mitochondrial membrane potential (ÎΚ(m)) and, therefore, the protomotive force were critically determined by respiratory complex I activity in healthy mitochondria, complex III activity was dominant for ÎΚ(m) during conditions of cytochrome-c deficiency. As a further important result, cellular bioenergetics in healthy, ATP-producing mitochondria was regulated by three parameter clusters that describe (1) mitochondrial respiration, (2) ATP production and consumption and (3) coupling of ATP-production and respiration. These parameter clusters resembled metabolic blocks and their intermediaries from top-down control analyses. However, parameter clusters changed significantly when cells changed from low to high ATP levels or when mitochondria were considered to be impaired by loss of cytochrome-c. This change suggests that the assumption of static metabolic blocks by conventional top-down control analyses is not valid under these conditions. Our approach is complementary to both ODE and top-down control analysis approaches and allows a better insight into cellular bioenergetics and its pathological alterations
Two experiments for the price of one? -- The role of the second oscillation maximum in long baseline neutrino experiments
We investigate the quantitative impact that data from the second oscillation
maximum has on the performance of wide band beam neutrino oscillation
experiments. We present results for the physics sensitivities to standard three
flavor oscillation, as well as results for the sensitivity to non-standard
interactions. The quantitative study is performed using an experimental setup
similar to the Fermilab to DUSEL Long Baseline Neutrino Experiment (LBNE). We
find that, with the single exception of sensitivity to the mass hierarchy, the
second maximum plays only a marginal role due to the experimental difficulties
to obtain a statistically significant and sufficiently background-free event
sample at low energies. This conclusion is valid for both water Cherenkov and
liquid argon detectors. Moreover, we confirm that non-standard neutrino
interactions are very hard to distinguish experimentally from standard
three-flavor effects and can lead to a considerable loss of sensitivity to
\theta_{13}, the mass hierarchy and CP violation.Comment: RevTex 4.1, 23 pages, 10 figures; v2: Typos corrected, very minor
clarifications; matches published version; v3: Fixed a typo in the first
equation in sec. III
The Out-of-Equilibrium Time-Dependent Gutzwiller Approximation
We review the recently proposed extension of the Gutzwiller approximation, M.
Schiro' and M. Fabrizio, Phys. Rev. Lett. 105, 076401 (2010), designed to
describe the out-of-equilibrium time-evolution of a Gutzwiller-type variational
wave function for correlated electrons. The method, which is strictly
variational in the limit of infinite lattice-coordination, is quite general and
flexible, and it is applicable to generic non-equilibrium conditions, even far
beyond the linear response regime. As an application, we discuss the quench
dynamics of a single-band Hubbard model at half-filling, where the method
predicts a dynamical phase transition above a critical quench that resembles
the sharp crossover observed by time-dependent dynamical mean field theory. We
next show that one can actually define in some cases a multi-configurational
wave function combination of a whole set of mutually orthogonal Gutzwiller wave
functions. The Hamiltonian projected in that subspace can be exactly evaluated
and is equivalent to a model of auxiliary spins coupled to non-interacting
electrons, closely related to the slave-spin theories for correlated electron
models. The Gutzwiller approximation turns out to be nothing but the mean-field
approximation applied to that spin-fermion model, which displays, for any
number of bands and integer fillings, a spontaneous symmetry breaking
that can be identified as the Mott insulator-to-metal transition.Comment: 25 pages. Proceedings of the Hvar 2011 Workshop on 'New materials for
thermoelectric applications: theory and experiment
Non-standard interactions versus non-unitary lepton flavor mixing at a neutrino factory
The impact of heavy mediators on neutrino oscillations is typically described
by non-standard four-fermion interactions (NSIs) or non-unitarity (NU). We
focus on leptonic dimension-six effective operators which do not produce
charged lepton flavor violation. These operators lead to particular
correlations among neutrino production, propagation, and detection non-standard
effects. We point out that these NSIs and NU phenomenologically lead, in fact,
to very similar effects for a neutrino factory, for completely different
fundamental reasons. We discuss how the parameters and probabilities are
related in this case, and compare the sensitivities. We demonstrate that the
NSIs and NU can, in principle, be distinguished for large enough effects at the
example of non-standard effects in the --sector, which basically
corresponds to differentiating between scalars and fermions as heavy mediators
as leading order effect. However, we find that a near detector at superbeams
could provide very synergistic information, since the correlation between
source and matter NSIs is broken for hadronic neutrino production, while NU is
a fundamental effect present at any experiment.Comment: 32 pages, 5 figures. Final version published in JHEP. v3: Typo in Eq.
(27) correcte
Mass hierarchy, 2-3 mixing and CP-phase with Huge Atmospheric Neutrino Detectors
We explore the physics potential of multi-megaton scale ice or water
Cherenkov detectors with low ( GeV) threshold. Using some proposed
characteristics of the PINGU detector setup we compute the distributions of
events versus neutrino energy and zenith angle , and study
their dependence on yet unknown neutrino parameters. The
regions are identified where the distributions have the highest sensitivity to
the neutrino mass hierarchy, to the deviation of the 2-3 mixing from the
maximal one and to the CP-phase. We evaluate significance of the measurements
of the neutrino parameters and explore dependence of this significance on the
accuracy of reconstruction of the neutrino energy and direction. The effect of
degeneracy of the parameters on the sensitivities is also discussed. We
estimate the characteristics of future detectors (energy and angle resolution,
volume, etc.) required for establishing the neutrino mass hierarchy with high
confidence level. We find that the hierarchy can be identified at --
level (depending on the reconstruction accuracies) after 5 years of
PINGU operation.Comment: 39 pages, 21 figures. Description of Fig.3 correcte
Testing matter effects in propagation of atmospheric and long-baseline neutrinos
We quantify our current knowledge of the size and flavor structure of the
matter effects in the evolution of atmospheric and long-baseline neutrinos
based solely on the analysis of the corresponding neutrino data. To this aim we
generalize the matter potential of the Standard Model by rescaling its
strength, rotating it away from the e-e sector, and rephasing it with respect
to the vacuum term. This phenomenological parametrization can be easily
translated in terms of non-standard neutrino interactions in matter. We show
that in the most general case, the strength of the potential cannot be
determined solely by atmospheric and long-baseline data. However its flavor
composition is very much constrained and the present determination of the
neutrino masses and mixing is robust under its presence. We also present an
update of the constraints arising from this analysis in the particular case in
which no potential is present in the e-mu and e-tau sectors. Finally we
quantify to what degree in this scenario it is possible to alleviate the
tension between the oscillation results for neutrinos and antineutrinos in the
MINOS experiment and show the relevance of the high energy part of the spectrum
measured at MINOS.Comment: PDFLaTeX file using JHEP3 class, 25 pages, 7 figures included.
Accepted for publication in JHE
IgM exacerbates glomerular disease progression in complement-induced glomerulopathy
While glomerular IgM deposition occurs in a variety of glomerular diseases the mechanism of deposition and its clinical significance remain controversial. Some have theorized IgM becomes passively trapped in areas of glomerulosclerosis. However, recent studies found that IgM specifically binds damaged glomeruli. Therefore, we tested whether natural IgM binds to neo-epitopes exposed after insults to the glomerulus and exacerbate disease in mice deficient in the complement regulatory protein factor H; a model of non-sclerotic and nonimmune-complex glomerular disease. Immunofluorescence microscopy demonstrated mesangial and capillary loop deposition of IgM while ultrastructural analysis found IgM deposition on endothelial cells and subendothelial areas. Factor H deficient mice lacking B cells were protected from renal damage, as evidenced by milder histologic lesions on light and electron microscopy. IgM, but not IgG, from wild-type mice bound to cultured murine mesangial cells. Furthermore, injection of purified IgM into mice lacking B cells bound within the glomeruli and induced proteinuria. A monoclonal natural IgM recognizing phospholipids also bound to glomeruli in vivo and induced albuminuria. Thus, our results indicate specific IgM antibodies bind to glomerular epitopes and that IgM contributes to the progression of glomerular damage in this mouse model of non-sclerotic glomerular disease
Pretreatment with a novel aquaporin 4 inhibitor, TGN-020, significantly reduces ischemic cerebral edema
We investigated the in vivo effects of a novel aquaporin 4 (AQP4) inhibitor 2-(nicotinamide)-1,3,4-thiadiazole, TGN-020, in a mouse model of focal cerebral ischemia using 7.0-T magnetic resonance imaging (MRI). Pretreatment with TGN-020 significantly reduced brain edema associated with brain ischemia, as reflected by percentage of brain swelling volume (%BSV), 12.1 ± 6.3% in the treated group, compared to (20.8 ± 5.9%) in the control group (p < 0.05), and in the size of cortical infarction as reflected by the percentage of hemispheric lesion volume (%HLV), 20.0 ± 7.6% in the treated group, compared to 30.0 ± 9.1% in the control group (p < 0.05). The study indicated the potential pharmacological use of AQP4 inhibition in reducing brain edema associated with focal ischemia
Mass hierarchy discrimination with atmospheric neutrinos in large volume ice/water Cherenkov detectors
Large mass ice/water Cherenkov experiments, optimized to detect low energy
(1-20 GeV) atmospheric neutrinos, have the potential to discriminate between
normal and inverted neutrino mass hierarchies. The sensitivity depends on
several model and detector parameters, such as the neutrino flux profile and
normalization, the Earth density profile, the oscillation parameter
uncertainties, and the detector effective mass and resolution. A proper
evaluation of the mass hierarchy discrimination power requires a robust
statistical approach. In this work, the Toy Monte Carlo, based on an extended
unbinned likelihood ratio test statistic, was used. The effect of each model
and detector parameter, as well as the required detector exposure, was then
studied. While uncertainties on the Earth density and atmospheric neutrino flux
profiles were found to have a minor impact on the mass hierarchy
discrimination, the flux normalization, as well as some of the oscillation
parameter (\Delta m^2_{31}, \theta_{13}, \theta_{23}, and \delta_{CP})
uncertainties and correlations resulted critical. Finally, the minimum required
detector exposure, the optimization of the low energy threshold, and the
detector resolutions were also investigated.Comment: 23 pages, 16 figure
Conceptualising Teacher Education for Inclusion: Lessons for the Professional Learning of Educators from Transnational and Cross-Sector Perspectives
Despite policy calling for enhanced inclusive practice within all schools and colleges, educators across Europe are facing increasing challenges when providing effective inclusive education for all students as a result of increased diversity within European society. This paper focuses on the development of our understanding of how to support educatorsâ professional learning around issues of diversity and inclusion. Specifically, it aims to explore what diversity looks like across countries, sectors, and roles, what challenges and dilemmas are posed for educators, and how new approaches to professional learning can support the educators across all sectors. The exploratory study described in the paper emerged from work undertaken as part of an Erasmus+ Strategic Partnership project called PROMISE (Promoting Inclusion in Society through Inclusion: Professional Dilemmas in Practice). Traditional approaches to professional learning to support teachersâ inclusive practice have tended to focus on discrete courses which address specific learning needs such as autism, literacy difficulties, or behavioural issues. The paper presents findings from a transnational study which indicate that the professional dilemmas facing educators are complex and unpredictable and argues, therefore, that educators require professional learning that is collaborative, interprofessional, and acknowledges that the challenges they face are multifaceted
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