4,000 research outputs found
Isoaspartate, Carbamoyl phosphate synthase-1, and carbonic anhydrase-III as biomarkers of liver injury
We had previously shown that alcohol consumption can induce cellular isoaspartate protein damage via an impairment of the activity of protein isoaspartyl methyltransferase (PIMT), an enzyme that triggers repair of isoaspartate protein damage. To further investigate the mechanism of isoaspartate accumulation, hepatocytes cultured from control or 4-week ethanol-fed rats were incubated in vitro with tubercidin or adenosine. Both these agents, known to elevate intracellular S-adenosylhomocysteine levels, increased cellular isoaspartate damage over that recorded following ethanol consumption in vivo. Increased isoaspartate damage was attenuated by treatment with betaine. To characterize isoaspartate-damaged proteins that accumulate after ethanol administration, rat liver cytosolic proteins were methylated using exogenous PIMT and 3H-S- adenosylmethionine and proteins resolved by gel electrophoresis. Three major protein bands of ~75-80 kDa, ~95-100 kDa, and ~155-160 kDa were identified by autoradiography. Column chromatography used to enrich isoaspartate-damaged proteins indicated that damaged proteins from ethanol-fed rats were similar to those that accrued in the livers of PIMT knockout (KO) mice. Carbamoyl phosphate synthase-1 (CPS-1) was partially purified and identified as the ~160kDa protein target of PIMT in ethanol-fed rats and in PIMT KO mice. Analysis of the liver proteome of 4-week ethanol-fed rats and PIMT KO mice demonstrated elevated cytosolic CPS-1 and betaine homocysteine S-methyltransferase-1 when compared to their respective controls, and a significant reduction of carbonic anhydrase-III (CA-III) evident only in ethanol-fed rats. Ethanol feeding of rats for 8 weeks resulted in a larger (~2.3-fold) increase in CPS-1 levels compared to 4- week ethanol feeding indicating that CPS-1 accumulation correlated with the duration of ethanol consumption. Collectively, our results suggest that elevated isoaspartate and CPS-1, and reduced CA-III levels could serve as biomarkers of hepatocellular injury
Predictors of the psychosocial impact of being a carer of people living with Parkinson’s disease: A systematic review
INTRODUCTION:Caring for a person with Parkinson's disease (PwP) can have a variety of negative consequences that may challenge their ability to continue their caring role. It is still unknown why some individuals adapt better than others in response to such burdens. This review is the first to synthesize and evaluate the evidence on the predictive factors of psychosocial outcomes in PwP carers.METHODS:Studies which identified predictors of psychosocial outcomes for unpaid carers were included. PsychINFO, EMBASE, AMED, BNI and CINAHL databases were searched, supplemented by scanning of references lists of included studies and relevant journals from 2008 onwards. Quality was assessed using the NICE methodology checklist for prognostic studies.RESULTS:Twenty-nine studies were included in the review, providing a low-level of evidence. Carer burden was investigated in 18 studies and mental health and quality of life (QoL) in seven studies each. PwP non-motor symptoms and QoL and carer depression were consistently identified as predictors for at least one psychosocial outcome. Demographics and disease factors were consistently found not to be predictors. Carer involvement and protective factors (e.g. social support, personality) demonstrated promising findings but studies were too few or factors measured inconsistently.CONCLUSION:Confident conclusions could not be drawn regarding the most important predictors that should be targeted in psychosocial interventions due to methodological weaknesses and lack of theoretical testing across the current literature. Future research should build upon psychological theory to gain a better understanding of the mechanisms that explain how carers adapt to caregiving
Shaping black holes with free fields
Starting from a metric Ansatz permitting a weak version of Birkhoff's theorem
we find static black hole solutions including matter in the form of free scalar
and p-form fields, with and without a cosmological constant \Lambda. Single
p-form matter fields permit multiple possibilities, including dyonic solutions,
self-dual instantons and metrics with Einstein-Kaelher horizons. The inclusion
of multiple p-forms on the other hand, arranged in a homogeneous fashion with
respect to the horizon geometry, permits the construction of higher dimensional
dyonic p-form black holes and four dimensional axionic black holes with flat
horizons, when \Lambda<0. It is found that axionic fields regularize black hole
solutions in the sense, for example, of permitting regular -- rather than
singular -- small mass Reissner-Nordstrom type black holes. Their cosmic string
and Vaidya versions are also obtained.Comment: 38 pages. v2: minor changes, published versio
A scalar field condensation instability of rotating anti-de Sitter black holes
Near-extreme Reissner-Nordstrom-anti-de Sitter black holes are unstable
against the condensation of an uncharged scalar field with mass close to the
Breitenlohner-Freedman bound. It is shown that a similar instability afflicts
near-extreme large rotating AdS black holes, and near-extreme hyperbolic
Schwarzschild-AdS black holes. The resulting nonlinear hairy black hole
solutions are determined numerically. Some stability results for (possibly
charged) scalar fields in black hole backgrounds are proved. For most of the
extreme black holes we consider, these demonstrate stability if the ``effective
mass" respects the near-horizon BF bound. Small spherical
Reissner-Nordstrom-AdS black holes are an interesting exception to this result.Comment: 34 pages; 13 figure
Bicarbonate and dichloroacetate: Evaluating pH altering therapies in a mouse model for metastatic breast cancer
BACKGROUND:The glycolytic nature of malignant tumors contributes to high levels of extracellular acidity in the tumor microenvironment. Tumor acidity is a driving force in invasion and metastases. Recently, it has been shown that buffering of extracellular acidity through systemic administration of oral bicarbonate can inhibit the spread of metastases in a mouse model for metastatic breast cancer. While these findings are compelling, recent assessments into the use of oral bicarbonate as a cancer intervention reveal limitations.METHODS:We posited that safety and efficacy of bicarbonate could be enhanced by dichloroacetate (DCA), a drug that selectively targets tumor cells and reduces extracellular acidity through inhibition of glycolysis. Using our mouse model for metastatic breast cancer (MDA-MB-231), we designed an interventional survival study where tumor bearing mice received bicarbonate, DCA, or DCA-bicarbonate (DB) therapies chronically.RESULTS:Dichloroacetate alone or in combination with bicarbonate did not increase systemic alkalosis in mice. Survival was longest in mice administered bicarbonate-based therapies. Primary tumor re-occurrence after surgeries is associated with survival rates. Although DB therapy did not significantly enhance oral bicarbonate, we did observe reduced pulmonary lesion diameters in this cohort. The DCA monotherapy was not effective in reducing tumor size or metastases or improving survival time. We provide in vitro evidence to suggest this outcome may be a function of hypoxia in the tumor microenvironment.CONCLUSIONS:DB combination therapy did not appear to enhance the effect of chronic oral bicarbonate. The anti-tumor effect of DCA may be dependent on the cancer model. Our studies suggest DCA efficacy is unpredictable as a cancer therapy and further studies are necessary to determine the role of this agent in the tumor microenvironment.This item is part of the UA Faculty Publications collection. For more information this item or other items in the UA Campus Repository, contact the University of Arizona Libraries at [email protected]
Hamiltonian thermodynamics of the Reissner-Nordstr\"om-anti-de Sitter black hole
We consider the Hamiltonian dynamics and thermodynamics of spherically
symmetric Einstein-Maxwell spacetimes with a negative cosmological constant. We
impose boundary conditions that enforce every classical solution to be an
exterior region of a Reissner-Nordstr\"om-anti-de Sitter black hole with a
nondegenerate Killing horizon, with the spacelike hypersurfaces extending from
the horizon bifurcation two-sphere to the asymptotically anti-de Sitter
infinity. The constraints are simplified by a canonical transformation, which
generalizes that given by Kucha\v{r} in the spherically symmetric vacuum
Einstein theory, and the theory is reduced to its true dynamical degrees of
freedom. After quantization, the grand partition function of a thermodynamical
grand canonical ensemble is obtained by analytically continuing the Lorentzian
time evolution operator to imaginary time and taking the trace. A~similar
analysis under slightly modified boundary conditions leads to the partition
function of a thermodynamical canonical ensemble. The thermodynamics in each
ensemble is analyzed, and the conditions that the (grand) partition function be
dominated by a classical Euclidean black hole solution are found. When these
conditions are satisfied, we recover in particular the Bekenstein-Hawking
entropy. The limit of a vanishing cosmological constant is briefly discussed.
(This paper is dedicated to Karel Kucha\v{r} on the occasion of his sixtieth
birthday.)Comment: 34 pages, REVTeX v3.0. (Minor corrections and presentational
revisions; added references.
The intrinsic shape of galaxy bulges
The knowledge of the intrinsic three-dimensional (3D) structure of galaxy
components provides crucial information about the physical processes driving
their formation and evolution. In this paper I discuss the main developments
and results in the quest to better understand the 3D shape of galaxy bulges. I
start by establishing the basic geometrical description of the problem. Our
understanding of the intrinsic shape of elliptical galaxies and galaxy discs is
then presented in a historical context, in order to place the role that the 3D
structure of bulges play in the broader picture of galaxy evolution. Our
current view on the 3D shape of the Milky Way bulge and future prospects in the
field are also depicted.Comment: Invited Review to appear in "Galactic Bulges" Editors: Laurikainen
E., Peletier R., Gadotti D. Springer Publishing. 24 pages, 7 figure
Search for Yukawa Production of a Light Neutral Higgs Boson at LEP
Within a Two-Higgs-Doublet Model (2HDM) a search for a light Higgs boson in
the mass range of 4-12 GeV has been performed in the Yukawa process e+e- -> b
bbar A/h -> b bbar tau+tau-, using the data collected by the OPAL detector at
LEP between 1992 and 1995 in e+e- collisions at about 91 GeV centre-of-mass
energy. A likelihood selection is applied to separate background and signal.
The number of observed events is in good agreement with the expected
background. Within a CP-conserving 2HDM type II model the cross-section for
Yukawa production depends on xiAd = |tan beta| and xihd = |sin alpha/cos beta|
for the production of the CP-odd A and the CP-even h, respectively, where tan
beta is the ratio of the vacuum expectation values of the Higgs doublets and
alpha is the mixing angle between the neutral CP-even Higgs bosons. From our
data 95% C.L. upper limits are derived for xiAd within the range of 8.5 to 13.6
and for xihd between 8.2 to 13.7, depending on the mass of the Higgs boson,
assuming a branching fraction into tau+tau- of 100%. An interpretation of the
limits within a 2HDM type II model with Standard Model particle content is
given. These results impose constraints on several models that have been
proposed to explain the recent BNL measurement of the muon anomalous magnetic
moment.Comment: 24 pages, 9 figures, Submitted to Euro. Phys. J.
Inhomogeneous Superconductivity in Condensed Matter and QCD
Inhomogeneous superconductivity arises when the species participating in the
pairing phenomenon have different Fermi surfaces with a large enough
separation. In these conditions it could be more favorable for each of the
pairing fermions to stay close to its Fermi surface and, differently from the
usual BCS state, for the Cooper pair to have a non zero total momentum. For
this reason in this state the gap varies in space, the ground state is
inhomogeneous and a crystalline structure might be formed. This situation was
considered for the first time by Fulde, Ferrell, Larkin and Ovchinnikov, and
the corresponding state is called LOFF. The spontaneous breaking of the space
symmetries in the vacuum state is a characteristic feature of this phase and is
associated to the presence of long wave-length excitations of zero mass. The
situation described here is of interest both in solid state and in elementary
particle physics, in particular in Quantum Chromo-Dynamics at high density and
small temperature. In this review we present the theoretical approach to the
LOFF state and its phenomenological applications using the language of the
effective field theories.Comment: RevTex, 83 pages, 26 figures. Submitted to Review of Modern Physic
Measurement of triple gauge boson couplings from WW production at LEP energies up to 189 GeV
A measurement of triple gauge boson couplings is presented, based on W-pair
data recorded by the OPAL detector at LEP during 1998 at a centre-of-mass
energy of 189 GeV with an integrated luminosity of 183 pb^-1. After combining
with our previous measurements at centre-of-mass energies of 161-183 GeV we
obtain k_g=0.97 +0.20 -0.16, g_1^z=0.991 +0.060 -0.057 and lambda_g=-0.110
+0.058 -0.055, where the errors include both statistical and systematic
uncertainties and each coupling is determined by setting the other two
couplings to their SM values. These results are consistent with the Standard
Model expectations.Comment: 28 pages, 8 figures, submitted to Eur. Phys. J.
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