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1.
Phys Rev Lett ; 132(19): 191402, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38804934

RESUMO

We present a top-down construction of a three-dimensional nonlocal theory of massive gravity. This "nonlocal massive gravity" (NLMG) is obtained as the gravitational theory induced by Einstein gravity on a brane inserted in anti-de Sitter space modified by an overall minus sign. The theory involves an infinite series of increasingly complicated higher-derivative corrections to the Einstein-Hilbert action, with the quadratic term coinciding with new massive gravity. We obtain an analytic formula for the quadratic action of NLMG and show that its linearized spectrum consists of an infinite tower of positive-energy massive spin-2 modes. We compute the Newtonian potential and show that the introduction of the infinite series of terms makes it behave as ∼1/r at short distances, as opposed to the logarithmic behavior encountered when the series is truncated at any finite order. We use this and input from brane-world holography to argue that the theory may contain asymptotically flat black hole solutions.

2.
Phys Rev Lett ; 131(17): 171601, 2023 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-37955507

RESUMO

The entanglement entropy of an arbitrary spacetime region A in a three-dimensional conformal field theory (CFT) contains a constant universal coefficient, F(A). For general theories, the value of F(A) is minimized when A is a round disk, F_{0}, and in that case it coincides with the Euclidean free energy on the sphere. We conjecture that, for general CFTs, the quantity F(A)/F_{0} is bounded above by the free scalar field result and below by the Maxwell field one. We provide strong evidence in favor of this claim and argue that an analogous conjecture in the four-dimensional case is equivalent to the Hofman-Maldacena bounds. In three dimensions, our conjecture gives rise to similar bounds on the quotients of various constants characterizing the CFT. In particular, it implies that the quotient of the stress-tensor two-point function coefficient and the sphere free energy satisfies C_{T}/F_{0}≤3/(4π^{2}log2-6ζ[3])≃0.14887 for general CFTs. We verify the validity of this bound for free scalars and fermions, general O(N) and Gross-Neveu models, holographic theories, N=2 Wess-Zumino models and general ABJM theories.

3.
Phys Rev Lett ; 131(11): 111603, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37774269

RESUMO

We construct generalized symmetries for linearized Einstein gravity in arbitrary dimensions. First-principle considerations in quantum field theory force generalized symmetries to appear in dual pairs. Verifying this prediction helps us find the full set of nontrivial conserved charges-associated, in equal parts, with 2-form and (D-2)-form currents. Their total number is D(D+1). We compute the quantum commutators of pairs of dual charges, showing that they are nonvanishing for regions whose boundaries are nontrivially linked with each other and zero otherwise, as expected on general grounds. We also consider general linearized higher-curvature gravities. These propagate, in addition to the usual graviton, a spin-0 mode as well as a massive ghostlike spin-2 mode. When the latter is absent, the theory is unitary and the dual-pairs principle is respected. In particular, we find that the number and types of charges remain the same as for Einstein gravity, and that they correspond to continuous generalizations of the Einsteinian ones.

4.
Phys Rev Lett ; 129(2): 021601, 2022 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-35867455

RESUMO

Rényi entropies, S_{n}, admit a natural generalization in the presence of global symmetries. These "charged Rényi entropies" are functions of the chemical potential µ conjugate to the charge contained in the entangling region and reduce to the usual notions as µâ†’0. For n=1, this provides a notion of charged entanglement entropy. In this Letter, we prove that for a general d(≥3)-dimensional conformal field theory, the leading correction to the uncharged entanglement entropy across a spherical entangling surface is quadratic in the chemical potential, positive definite, and universally controlled (up to fixed d-dependent constants) by the coefficients C_{J} and a_{2}. These fully characterize, for a given theory, the current correlators ⟨JJ⟩ and ⟨TJJ⟩, as well as the energy flux measured at infinity produced by the insertion of the current operator. Our result is motivated by analytic holographic calculations for a special class of higher-curvature gravities coupled to a (d-2) form in general dimensions as well as for free fields in d=4. A proof for general theories and dimensions follows from previously known universal identities involving the magnetic response of twist operators introduced in A. Belin et al. [J. High Energy Phys. 12 (2013) 059.JHEPFG1029-847910.1007/JHEP12(2013)059] and basic thermodynamic relations.

5.
Phys Rev Lett ; 122(7): 071602, 2019 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-30848622

RESUMO

We present several results concerning the free energy of odd-dimensional conformal field theories (CFTs) on squashed spheres. First, we propose a formula which computes this quantity for holographic CFTs dual to higher-curvature gravities with second-order linearized equations of motion. As opposed to standard on-shell action methods for Taub geometries, our formula only involves a simple evaluation of the corresponding bulk Lagrangian on an auxiliary pure anti-de Sitter (AdS) space. The expression is closely related to the function determining the possible AdS vacua of the bulk theory in question, which we argue to act as a generating functional from which correlation functions of the boundary stress tensor can be easily characterized. Finally, based on holographic results and free-field numerical calculations, we conjecture that the subleading term in the squashing-parameter free-energy expansion is universally controlled by the stress-tensor three-point function charge t_{4} for general (2+1)-dimensional CFTs.

6.
Phys Rev Lett ; 115(2): 021602, 2015 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-26207459

RESUMO

We study the contribution to the entanglement entropy of (2+1)-dimensional conformal field theories (CFTs) coming from a sharp corner in the entangling surface. This contribution is encoded in a function a(θ) of the corner opening angle, and was recently proposed as a measure of the degrees of freedom in the underlying CFT. We show that the ratio a(θ)/C(T), where C(T) is the central charge in the stress tensor correlator, is an almost universal quantity for a broad class of theories including various higher-curvature holographic models, free scalars, and fermions, and Wilson-Fisher fixed points of the O(N) models with N=1,2,3. Strikingly, the agreement between these different theories becomes exact in the limit θ→π, where the entangling surface approaches a smooth curve. We thus conjecture that the corresponding ratio is universal for general CFTs in three dimensions.

7.
PLoS One ; 9(11): e112189, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25380052

RESUMO

To date, no effective method exists that predicts the response to preoperative chemoradiation (CRT) in locally advanced rectal cancer (LARC). Nevertheless, identification of patients who have a higher likelihood of responding to preoperative CRT could be crucial in decreasing treatment morbidity and avoiding expensive and time-consuming treatments. The aim of this study was to identify signatures or molecular markers related to response to pre-operative CRT in LARC. We analyzed the gene expression profiles of 26 pre-treatment biopsies of LARC (10 responders and 16 non-responders) without metastasis using Human WG CodeLink microarray platform. Two hundred and fifty seven genes were differentially over-expressed in the responder patient subgroup. Ingenuity Pathway Analysis revealed a significant ratio of differentially expressed genes related to cancer, cellular growth and proliferation pathways, and c-Myc network. We demonstrated that high Gng4, c-Myc, Pola1, and Rrm1 mRNA expression levels was a significant prognostic factor for response to treatment in LARC patients (p<0.05). Using this gene set, we were able to establish a new model for predicting the response to CRT in rectal cancer with a sensitivity of 60% and 100% specificity. Our results reflect the value of gene expression profiling to gain insight about the molecular pathways involved in the response to treatment of LARC patients. These findings could be clinically relevant and support the use of mRNA levels when aiming to identify patients who respond to CRT therapy.


Assuntos
Perfilação da Expressão Gênica , Neoplasias Retais/genética , Neoplasias Retais/terapia , Idoso , Quimiorradioterapia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Prognóstico , Neoplasias Retais/diagnóstico , Reto/metabolismo , Reto/patologia , Resultado do Tratamento
8.
PLoS One ; 8(9): e74034, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24040155

RESUMO

Preoperative chemoradiation significantly improves oncological outcome in locally advanced rectal cancer. However there is no effective method of predicting tumor response to chemoradiation in these patients. Peripheral blood mononuclear cells have emerged recently as pathology markers of cancer and other diseases, making possible their use as therapy predictors. Furthermore, the importance of the immune response in radiosensivity of solid organs led us to hypothesized that microarray gene expression profiling of peripheral blood mononuclear cells could identify patients with response to chemoradiation in rectal cancer. Thirty five 35 patients with locally advanced rectal cancer were recruited initially to perform the study. Peripheral blood samples were obtained before neaodjuvant treatment. RNA was extracted and purified to obtain cDNA and cRNA for hybridization of microarrays included in Human WG CodeLink bioarrays. Quantitative real time PCR was used to validate microarray experiment data. Results were correlated with pathological response, according to Mandard´s criteria and final UICC Stage (patients with tumor regression grade 1-2 and downstaging being defined as responders and patients with grade 3-5 and no downstaging as non-responders). Twenty seven out of 35 patients were finally included in the study. We performed a multiple t-test using Significance Analysis of Microarrays, to find those genes differing significantly in expression, between responders (n = 11) and non-responders (n = 16) to CRT. The differently expressed genes were: BC 035656.1, CIR, PRDM2, CAPG, FALZ, HLA-DPB2, NUPL2, and ZFP36. The measurement of FALZ (p = 0.029) gene expression level determined by qRT-PCR, showed statistically significant differences between the two groups. Gene expression profiling reveals novel genes in peripheral blood samples of mononuclear cells that could predict responders and non-responders to chemoradiation in patients with locally advanced rectal cancer. Moreover, our investigation added further evidence to the importance of mononuclear cells' mediated response in the neoadjuvant treatment of rectal cancer.


Assuntos
Biomarcadores Tumorais , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Leucócitos Mononucleares/metabolismo , Neoplasias Retais/genética , Adulto , Idoso , Feminino , Humanos , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/efeitos da radiação , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/radioterapia , Reprodutibilidade dos Testes , Resultado do Tratamento
9.
J Colloid Interface Sci ; 362(1): 235-41, 2011 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-21737091

RESUMO

The coalescence mechanism of a particle-laden drop resting at an oil-water interface has been studied. Two mechanisms for drop coalescence are observed; (i) complete coalescence, in which the drop experiences total coalescence in one event, and (ii) partial coalescence, where a drop is observed to separate during coalescence, producing a smaller secondary drop that rebounds and comes to rest at the planar oil-water interface. For particle-laden drops of approximately 4mm in diameter, we show the critical condition for partial to complete coalescence to be dependent on the particle concentration, and the interparticle interaction energy. Colloidal silica spheres dispersed in 10(-4) M KNO(3) electrolyte solution are highly charged and remain dispersed in the drop. By increasing the solids concentration, we measure the transition from partial to complete coalescence at 20 wt.%. However, this critical condition can be reduced by increasing the interparticle interaction energy. In 1 M KNO(3) electrolyte solution, the particle surface charge is sufficiently screened such that particle clusters readily form in the water drop. With particle clustering, transition from partial to complete coalescence is measured at 8 wt.% solids.

10.
J Surg Res ; 153(2): 224-30, 2009 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-18952228

RESUMO

OBJECTIVE: To investigate the effect of parenteral administration of vitamin C on neutrophil apoptosis by determining Fas receptor expression and caspase-3, poly (ADP-ribose) polymerase (PARP), and Bcl-2 levels in neutrophils from septic abdominal surgery patients. STUDY DESIGN: Twenty septic abdominal surgery patients were studied in a prospective, randomized, double-blinded clinical trial. A group of healthy volunteers (n = 10) constituted a reference group for baseline parameter values. The patients were randomly assigned to a vitamin C-treated (n = 10) or placebo-treated (n = 10) group. For a 6-d period from 12 h post-surgery, the vitamin C group received 450 mg/d of the vitamin in 3 doses and the placebo group an identical administration of 5% dextrose. Early-morning peripheral blood samples were obtained daily from 24 h after vitamin C administration until d 6 post-surgery (T1d-T6d). RESULTS: Vitamin C group showed a nonsignificant reduction in Fas (CD95) expression on CD15-positive peripheral blood neutrophils, significantly decreased caspase-3, and PARP levels (caspase-3: T4d: P < 0.05, T5d: P < 0.05, T6d P < 0.01; and PARP: T3d: P < 0.05, T4d: P < 0.05, T6d: P < 0.05), and significantly increased Bcl-2 levels (T3d: P = 0.001) versus placebo group. CONCLUSIONS: Postoperative vitamin C treatment of septic abdominal surgery patients exerts an antiapoptotic effect on peripheral blood neutrophils, reducing caspase-3 and PARP levels, and increasing Bcl-2 levels. However, these antiapoptotic effects are not maintained at all time points.


Assuntos
Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Ácido Ascórbico/farmacologia , Neutrófilos/efeitos dos fármacos , Sepse/cirurgia , Idoso , Caspase 3/metabolismo , Procedimentos Cirúrgicos do Sistema Digestório , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Poli(ADP-Ribose) Polimerases/metabolismo , Cuidados Pós-Operatórios , Estudos Prospectivos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Receptor fas/metabolismo
11.
Am J Hypertens ; 18(6): 871-7, 2005 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15925750

RESUMO

BACKGROUND: This study analyzed whether hypertension induced by N(omega)-nitro-l-arginine methyl ester (L-NAME) is associated with dysregulation of the main antioxidant enzymes (superoxide dismutase [SOD], catalase, glutathione peroxidase [GPX], and glutathione reductase [GR]) and whether chronic administration of tempol ameliorates this hypertension. METHODS: Four groups of male Wistar rats were used: 1) control rats; 2) rats treated with L-NAME (35 mg/100 mL in drinking fluid); 3) rats treated with tempol (18 mg/100 mL in drinking fluid); and 4) rats treated with L-NAME plus tempol. All treatments were maintained for 6 weeks. Body weight, systolic blood pressure (BP) determined by the tail-cuff method, and heart rate were measured once per week. At the end of the experimental period, direct BP and morphologic, metabolic, plasma, and renal variables were measured. Enzymatic activities were measured in the kidney (cortex and medulla) and heart (right and left ventricles). RESULTS: Rats with L-NAME-induced hypertension showed increased copper-zinc (Cu-Zn) SOD activity in the renal cortex and medulla and the left and right ventricles, which was reduced by tempol administration. The manganese (Mn) SOD activity was increased by L-NAME and reduced by tempol in the renal cortex but was unchanged in other tissues. Catalase activity was not affected by L-NAME or tempol treatments in any tissue. Both GPX and GR activities were increased by L-NAME and reduced by tempol in the renal cortex and medulla but were not affected in the ventricles. Tempol reduced BP and total urinary excretion of 8-hydroxy-2'-deoxyguanosine in L-NAME-treated animals but did not affect either variable in controls. CONCLUSIONS: We conclude that L-NAME-induced hypertension is associated with an upregulation of antioxidant SOD, GPX, and GR activities. Moreover, the results indicate that tempol attenuates hypertension on nitric oxide-deficient rats and that oxidative stress participates in the established phase of this type of hypertension.


Assuntos
Antioxidantes/uso terapêutico , Óxidos N-Cíclicos/uso terapêutico , Hipertensão/tratamento farmacológico , Óxido Nítrico/antagonistas & inibidores , Oxirredutases/metabolismo , 8-Hidroxi-2'-Desoxiguanosina , Animais , Biomarcadores/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Catalase/efeitos dos fármacos , Catalase/metabolismo , Desoxiguanosina/análogos & derivados , Desoxiguanosina/urina , Modelos Animais de Doenças , Inibidores Enzimáticos/toxicidade , Ensaio de Imunoadsorção Enzimática , Glutationa Peroxidase/efeitos dos fármacos , Glutationa Peroxidase/metabolismo , Glutationa Redutase/efeitos dos fármacos , Glutationa Redutase/metabolismo , Frequência Cardíaca/efeitos dos fármacos , Frequência Cardíaca/fisiologia , Ventrículos do Coração/enzimologia , Ventrículos do Coração/patologia , Hipertensão/induzido quimicamente , Hipertensão/enzimologia , Córtex Renal/enzimologia , Córtex Renal/patologia , Medula Renal/enzimologia , Medula Renal/patologia , Masculino , NG-Nitroarginina Metil Éster/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Oxirredutases/efeitos dos fármacos , Ratos , Ratos Wistar , Espectrofotometria , Marcadores de Spin , Superóxido Dismutase/efeitos dos fármacos , Superóxido Dismutase/metabolismo
12.
Am J Physiol Endocrinol Metab ; 289(5): E776-83, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-15941780

RESUMO

This study evaluated the activity of cardiac and renal antioxidant enzymes [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), and glutathione reductase (GR)] and whether chronic treatment with tempol, a cell membrane-permeable SOD mimetic, ameliorates the hypertension of hyperthyroidism. Two experiments were performed. In experiment I, the following four groups of male Wistar rats were used: control group and three groups that received thyroxine (T4) at 10, 50, or 75 microg x rat(-1) x day(-1). In experiment II, tempol was orally administered (18 mg x kg(-1) x day(-1)) to control and T4-treated (75 microg x rat(-1) x day(-1)) rats. All treatments were maintained for 6 wk. Body weight, tail systolic blood pressure (BP), and heart rate were measured one time a week, and direct BP and morphological, metabolic, plasma, and renal variables were measured at the end of the experiment. Enzymatic activities were measured in renal cortex and medulla and right and left ventricles. In renal cortex, SOD activity was decreased in the T4-75 group, and there was a dose-related increase in CAT activity and decrease in GPX and GR activities in T4-treated groups. Activity of all antioxidant enzymes was reduced in left ventricle in T4-50 and T4-75 groups and in right ventricle in the T4-75 group. Tempol reduced BP, plasma malondialdehyde, and total urinary excretion of F2 isoprostanes in hypertensive hyperthyroid rats but not in controls. Tempol did not improve cardiac hypertrophy, proteinuria, or creatinine clearance in hyperthyroid rats. In conclusion, the results obtained indicate that the activity of SOD, GPX, and GR in renal and cardiac tissues is decreased in hyperthyroidism and that antioxidant treatment with tempol ameliorates T4-induced hypertension.


Assuntos
Antioxidantes/farmacologia , Óxidos N-Cíclicos/farmacologia , Hipertireoidismo/tratamento farmacológico , Hipertireoidismo/enzimologia , Rim/enzimologia , Miocárdio/enzimologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Catalase/metabolismo , Dinoprosta/análogos & derivados , Dinoprosta/urina , Glutationa Peroxidase/metabolismo , Glutationa Redutase/metabolismo , Frequência Cardíaca/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Hipertensão/enzimologia , Hipertensão/etiologia , Hipertireoidismo/complicações , Masculino , Malondialdeído/sangue , Ratos , Ratos Wistar , Marcadores de Spin , Superóxido Dismutase/metabolismo , Tiroxina/farmacologia
13.
New Phytol ; 156(3): 409-415, 2002 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33873571

RESUMO

• The effects of salt stress and adaptation on salicylic acid (SA) content and on antioxidant and lipoxygenase (LOX) enzyme activities were studied in tomato (Lycopersicon esculentum cv. Pera) cells. • NaCl-adapted cells were obtained from calli adapted to 100 mm NaCl by successive subcultures in medium supplemented with 100 mm NaCl. Salt stress treatments consisted of the addition of 100 mm NaCl to cells. • Adapted cells contained a lower concentration of SA than unadapted cells. The lower manganese-containing superoxide dismutase (Mn-SOD) and LOX activities as well as the higher glutathione reductase (GR) and ascorbate peroxidase (APX) activities in adapted cells than in unadapted cells could be correlated with the development of salt adaptation. Salt stress increased APX and LOX activities as well as lipid peroxidation in unadapted cells and increased Mn-SOD activity in both types of cells. Application of 200 µm SA + 100 mm NaCl inhibited APX activity in both unadapted and adapted cells, induced the Mn-SOD in adapted cells and increased lipid peroxidation in unadapted cells. • Our data indicate that adaptation of tomato cells to NaCl results in a higher tolerance to NaCl-induced oxidative stress and suggest a role for SA in this response.

14.
New Phytol ; 152(1): 91-96, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35974481

RESUMO

• The involvement of lipoxygenase and antioxidant enzyme activities as well as hydrogen peroxide (H2 O2 ) accumulation are reported during early infection steps in alfalfa (Medicago sativa) roots inoculated either with a wild type Sinorhizobium meliloti or with a mutant defective in Nod-factor synthesis (Nod C- ). • Compatibility between M. sativa and Rhizobium correlates, at least in part, with an increase in the activities of these enzymes, particularly catalase and lipoxygenase, during the preinfection period (up to 12 h). The mutant strain, defective in Nod-factor biosynthesis, showed a decrease in all enzyme activities assayed, and an increase in H2 O2 accumulation. • Enhancement of scavenging activities for several reactive oxygen species correlated with compatibility of the S. meliloti-alfalfa symbiosis, whereas the Nod C- strain triggered a defence response. Nod factors were essential to suppress this response. • Increase in lipoxygenase and lipid hydroperoxide decomposing activities, observed during the first hours after inoculation with a compatible strain, could be related to tissue differentiation and/or the production of signal molecules involved in autoregulation of nodulation by the plant.

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