151 research outputs found
Gedanken experiments on nearly extremal black holes and the Third Law
A gedanken experiment in which a black hole is pushed to spin at its maximal
rate by tossing into it a test body is considered. After demonstrating that
this is kinematically possible for a test body made of reasonable matter, we
focus on its implications for black hole thermodynamics and the apparent
violation of the third law (unattainability of the extremal black hole). We
argue that this is not an actual violation, due to subtleties in the absorption
process of the test body by the black hole, which are not captured by the
purely kinematic considerations.Comment: v2: minor edits, references added; v3: minor edits to match published
versio
Gravity from Quantum Information
It is suggested that the Einstein equation can be derived from Landauer's
principle applied to an information erasing process at a local Rindler horizon
and Jacobson's idea linking the Einstein equation with thermodynamics. When
matter crosses the horizon, the information of the matter disappears and the
horizon entanglement entropy increases to compensate the entropy reduction. The
Einstein equation describes an information-energy relation during this process,
which implies that entropic gravity is related to the quantum entanglement of
the vacuum and has a quantum information theoretic origin.Comment: 7 pages, revtex4-1, 2 figures, recent supporting results adde
The relativistic fluid dual to vacuum Einstein gravity
We present a construction of a (d+2)-dimensional Ricci-flat metric
corresponding to a (d+1)-dimensional relativistic fluid, representing
holographically the hydrodynamic regime of a (putative) dual theory. We show
how to obtain the metric to arbitrarily high order using a relativistic
gradient expansion, and explicitly carry out the computation to second order.
The fluid has zero energy density in equilibrium, which implies
incompressibility at first order in gradients, and its stress tensor (both at
and away from equilibrium) satisfies a quadratic constraint, which determines
its energy density away from equilibrium. The entire dynamics to second order
is encoded in one first order and six second order transport coefficients,
which we compute. We classify entropy currents with non-negative divergence at
second order in relativistic gradients. We then verify that the entropy current
obtained by pulling back to the fluid surface the area form at the null horizon
indeed has a non-negative divergence. We show that there are distinct
near-horizon scaling limits that are equivalent either to the relativistic
gradient expansion we discuss here, or to the non-relativistic expansion
associated with the Navier-Stokes equations discussed in previous works. The
latter expansion may be recovered from the present relativistic expansion upon
taking a specific non-relativistic limit.Comment: 29 pages, 1 figure; v2: added comments and references, published
versio
Conservative entropic forces
Entropic forces have recently attracted considerable attention as ways to
reformulate, retrodict, and perhaps even "explain'" classical Newtonian gravity
from a rather specific thermodynamic perspective. In this article I point out
that if one wishes to reformulate classical Newtonian gravity in terms of an
entropic force, then the fact that Newtonian gravity is described by a
conservative force places significant constraints on the form of the entropy
and temperature functions. (These constraints also apply to entropic
reinterpretations of electromagnetism, and indeed to any conservative force
derivable from a potential.)
The constraints I will establish are sufficient to present real and
significant problems for any reasonable variant of Verlinde's entropic gravity
proposal, though for technical reasons the constraints established herein do
not directly impact on either Jacobson's or Padmanabhan's versions of entropic
gravity. In an attempt to resolve these issues, I will extend the usual notion
of entropic force to multiple heat baths with multiple "temperatures'" and
multiple "entropies".Comment: V1: 21 pages; no figures. V2: now 24 pages. Two new sections (reduced
mass formulation, decoherence). Many small clarifying comments added
throughout the text. Several references added. V3: Three more references
added. V4: now 25 pages. Some extra discussion on the relation between
Verlinde's scenario and the Jacobson and Padmanabhan scenarios. This version
accepted for publication in JHE
Tumor tissue levels of Tissue Inhibitor of Metalloproteinases-1 (TIMP-1) and outcome following adjuvant chemotherapy in premenopausal lymph node-positive breast cancer patients: A retrospective study
<p>Abstract</p> <p>Background</p> <p>We have previously demonstrated that high tumor tissue levels of TIMP-1 are associated with no or limited clinical benefit from chemotherapy with CMF and anthracyclines in metastatic breast cancer patients. Here, we extend our investigations to the adjuvant setting studying outcome after adjuvant chemotherapy in premenopausal lymph node-positive patients. We hypothesize that TIMP-1 high tumors are less sensitive to chemotherapy and accordingly that high tumor tissue levels are associated with shorter survival.</p> <p>Methods</p> <p>From our original retrospectively collected tumor samples we selected a group of 525 pre-menopausal lymph node-positive patients (adjuvant treatment: CMF, 324 patients; anthracycline-based, 99 patients; no adjuvant chemotherapy, 102 patients). TIMP-1 levels were measured using ELISA in cytosolic extracts of frozen primary tumors. TIMP-1 was analyzed as a continuous variable and as a dichotomized one using the median TIMP-1 concentration as a cut point between high and low TIMP-1 groups. We analyzed the benefit of adjuvant CMF and anthracyclines in univariate and multivariable survival models; endpoints were disease-free (DFS) and overall survival (OS).</p> <p>Results</p> <p>In this selected cohort of high-risk patients, and in the subgroup of patients receiving no adjuvant therapy, TIMP-1 was not associated with prognosis. In the subgroup of patients treated with anthracyclines, when analyzed as a continuous variable we observed a tendency for increasing TIMP-1 levels to be associated with shorter DFS (multivariable analysis, HR 1.75, 95% CI 1.00-3.07, P = 0.05) and a significant association between increasing TIMP-1 and shorter OS in both univariate (HR 3.52, 95% CI 1.54-8.06, P = 0.003) and multivariable analyses (HR 4.19, 95% CI 1.67-10.51, P = 0.002). No statistically significant association between TIMP-1 and DFS was observed in the CMF-treated patients although high TIMP-1 was associated with shorter OS when analyzed as a dichotomized variable (HR 1.64, 95% CI 1.02-2.65, P = 0.04).</p> <p>Conclusion</p> <p>In the subgroup of patients receiving adjuvant chemotherapy we found an association between shorter survival after treatment in TIMP-1 high patients compared with TIMP-1 low patients, especially in patients receiving anthracycline-based therapy. This suggests that high tumor tissue levels of TIMP-1 might be associated with reduced benefit from classical adjuvant chemotherapy. Our findings should be validated in larger prospective studies.</p
f(R) theories
Over the past decade, f(R) theories have been extensively studied as one of
the simplest modifications to General Relativity. In this article we review
various applications of f(R) theories to cosmology and gravity - such as
inflation, dark energy, local gravity constraints, cosmological perturbations,
and spherically symmetric solutions in weak and strong gravitational
backgrounds. We present a number of ways to distinguish those theories from
General Relativity observationally and experimentally. We also discuss the
extension to other modified gravity theories such as Brans-Dicke theory and
Gauss-Bonnet gravity, and address models that can satisfy both cosmological and
local gravity constraints.Comment: 156 pages, 14 figures, Invited review article in Living Reviews in
Relativity, Published version, Comments are welcom
Measurement of the νe -Nucleus Charged-Current Double-Differential Cross Section at «eν »=2.4 GeV Using NOvA
The inclusive electron neutrino charged-current cross section is measured in the NOvA near detector using 8.02×1020 protons-on-target in the NuMI beam. The sample of GeV electron neutrino interactions is the largest analyzed to date and is limited by ≃17% systematic rather than the ≃7.4% statistical uncertainties. The double-differential cross section in final-state electron energy and angle is presented for the first time, together with the single-differential dependence on Q2 (squared four-momentum transfer) and energy, in the range 1 GeV≤Eν<6 GeV. Detailed comparisons are made to the predictions of the GENIE, GiBUU, NEUT, and NuWro neutrino event generators. The data do not strongly favor a model over the others consistently across all three cross sections measured, though some models have especially good or poor agreement in the single differential cross section vs Q2
Measurement of the Nucleus Charged-Current Double-Differential Cross Section at 2.4 GeV using NOvA
The inclusive electron neutrino charged-current cross section is measured in
the NOvA near detector using protons-on-target (POT) in the
NuMI beam. The sample of GeV electron neutrino interactions is the largest
analyzed to date and is limited by 17\% systematic rather than the
7.4\% statistical uncertainties. The double-differential cross section
in final-state electron energy and angle is presented for the first time,
together with the single-differential dependence on (squared
four-momentum transfer) and energy, in the range 1 GeV 6 GeV.
Detailed comparisons are made to the predictions of the GENIE, GiBUU, NEUT, and
NuWro neutrino event generators. The data do not strongly favor a model over
the others consistently across all three cross sections measured, though some
models have especially good or poor agreement in the single differential cross
section vs.
TIMP-1 Induces an EMT-Like Phenotypic Conversion in MDCK Cells Independent of Its MMP-Inhibitory Domain
Matrix metalloproteinases (MMPs) and their endogenous inhibitors (TIMPs) regulate epithelial-mesenchymal transition (EMT) critical for the development of epithelial organs as well as cancer cell invasion. TIMP-1 is frequently overexpressed in several types of human cancers and serves as a prognostic marker. The present study investigates the roles of TIMP-1 on the EMT process and formation of the lumen-like structure in a 3D Matrigel culture of MDCK cells. We show that TIMP-1 overexpression effectively prevents cell polarization and acinar-like structure formation. TIMP-1 induces expression of the developmental EMT transcription factors such as SLUG, TWIST, ZEB1 and ZEB2, leading to downregulation of epithelial marker and upregulation of mesenchymal markers. Importantly, TIMP-1′s ability to induce the EMT-like process is independent of its MMP-inhibitory domain. To our surprise, TIMP-1 induces migratory and invasive properties in MDCK cells. Here, we present a novel finding that TIMP-1 signaling upregulates MT1-MMP and MMP-2 expression, and potentiates MT1-MMP activation of pro-MMP-2, contributing to tumor cell invasion. In spite of the fact that TIMP-1, as opposed to TIMP-2, does not interact with and inhibit MT1-MMP, TIMP-1 may act as a key regulator of MT1-MMP/MMP-2 axis. Collectively, our findings suggest a model in which TIMP-1 functions as a signaling molecule and also as an endogenous inhibitor of MMPs. This concept represents a paradigm shift in the current view of TIMP-1/MT1-MMP interactions and functions during cancer development/progression
Timp1 interacts with beta-1 integrin and CD63 along melanoma genesis and confers anoikis resistance by activating PI3-K signaling pathway independently of Akt phosphorylation
Background: Anoikis resistance is one of the abilities acquired along tumor progression. This characteristic is associated with metastasis development, since tumorigenic cells must survive independently of cell-matrix interactions in this process. in our laboratory, it was developed a murine melanocyte malignant transformation model associated with a sustained stressful condition. After subjecting melan-a melanocytes to 1, 2, 3 and 4 cycles of anchorage impediment, anoikis resistant cells were established and named 1C, 2C, 3C and 4C, respectively. These cells showed altered morphology and PMA independent cell growth, but were not tumorigenic, corresponding to pre-malignant cells. After limiting dilution of 4C pre-malignant cells, melanoma cell lines with different characteristics were obtained. Previous data from our group showed that increased Timp1 expression correlated with anoikis-resistant phenotype. Timp1 was shown to confer anchorage-independent growth capability to melan-a melanocytes and render melanoma cells more aggressive when injected into mice. However, the mechanisms involved in anoikis regulation by Timp1 in tumorigenic cells are not clear yet.Methods: the beta 1-integrin and Timp1 expression were evaluated by Western blotting and CD63 protein expression by flow cytometry using specific antibodies. To analyze the interaction among Timp1, CD63 and beta 1-integrin, immunoprecipitation assays were performed, anoikis resistance capability was evaluated in the presence or not of the PI3-K inhibitors, Wortmannin and LY294002. Relative expression of TIMP1 and CD63 in human metastatic melanoma cells was analyzed by real time PCR.Results: Differential association among Timp1, CD63 and beta 1-integrins was observed in melan-a melanocytes, 4C pre-malignant melanocytes and 4C11- and 4C11+ melanoma cells. Timp1 present in conditioned medium of melanoma cells rendered melan-a melanocytes anoikis-resistant through PI3-K signaling pathway independently of Akt activation. in human melanoma cell lines, in which TIMP1 and beta-1 integrin were also found to be interacting, TIMP1 and CD63 levels together was shown to correlate significantly with colony formation capacity.Conclusions: Our results show that Timp1 is assembled in a supramolecular complex containing CD63 and beta 1-integrins along melanoma genesis and confers anoikis resistance by activating PI3-K signaling pathway, independently of Akt phosphorylation. in addition, our data point TIMP1, mainly together with CD63, as a potential biomarker of melanoma.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Universidade Federal de São Paulo, Dept Pharmacol, São Paulo, BrazilUniversidade Federal de São Paulo, Microbiol Immunol & Parasitol Dept, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biochem, São Paulo, BrazilLudwig Inst Canc Res, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Pharmacol, São Paulo, BrazilUniversidade Federal de São Paulo, Microbiol Immunol & Parasitol Dept, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biochem, São Paulo, BrazilFAPESP: 2011/12306-1FAPESP: 2010/18715-8CAPES: 2867/10Web of Scienc
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