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1.
Phys Rev Lett ; 119(5): 056402, 2017 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-28949722

RESUMO

Starting from the (Hubbard) model of an atom, we demonstrate that the uniqueness of the mapping from the interacting to the noninteracting Green function, G→G_{0}, is strongly violated, by providing numerous explicit examples of different G_{0} leading to the same physical G. We argue that there are indeed infinitely many such G_{0}, with numerous crossings with the physical solution. We show that this rich functional structure is directly related to the divergence of certain classes of (irreducible vertex) diagrams, with important consequences for traditional many-body physics based on diagrammatic expansions. Physically, we ascribe the onset of these highly nonperturbative manifestations to the progressive suppression of the charge susceptibility induced by the formation of local magnetic moments and/or resonating valence bond (RVB) states in strongly correlated electron systems.

2.
Ann Oncol ; 27(8): 1579-85, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27457310

RESUMO

BACKGROUND: Anti-angiogenic therapies are effective in metastatic renal cell carcinoma (mRCC), but resistance is inevitable. A dual-inhibition strategy focused on hypoxia-inducible factor (HIF) is hypothesized to be active in this refractory setting. CRLX101 is an investigational camptothecin-containing nanoparticle-drug conjugate (NDC), which durably inhibits HIF1α and HIF2α in preclinical models and in gastric cancer patients. Synergy was observed in the preclinical setting when combining this NDC and anti-angiogenic agents, including bevacizumab. PATIENTS AND METHODS: Patients with refractory mRCC were treated every 2 weeks with bevacizumab (10 mg/kg) and escalating doses of CRLX101 (12, 15 mg/m(2)) in a 3 + 3 phase I design. An expansion cohort of 10 patients was treated at the recommended phase II dose (RP2D). Patients were treated until progressive disease or prohibitive toxicity. Adverse events (AEs) were assessed using CTCAE v4.0 and clinical outcome using RECIST v1.1. RESULTS: Twenty-two patients were response-evaluable in an investigator-initiated trial at two academic medical centers. RCC histologies included clear cell (n = 12), papillary (n = 5), chromophobe (n = 2), and unclassified (n = 3). Patients received a median of two prior therapies, with at least one prior vascular endothelial tyrosine kinase inhibitor therapy (VEGF-TKI). No dose-limiting toxicities were observed. Grade ≥3 AEs related to CRLX101 included non-infectious cystitis (5 events), fatigue (3 events), anemia (2 events), diarrhea (2 events), dizziness (2 events), and 7 other individual events. Five of 22 patients (23%) achieved partial responses, including 3 of 12 patients with clear cell histology and 2 of 10 patients (20%) with non-clear cell histology. Twelve of 22 patients (55%) achieved progression-free survival (PFS) of >4 months. CONCLUSIONS: CRLX101 combined with bevacizumab is safe in mRCC. This combination fulfilled the protocol's predefined threshold for further examination with responses and prolonged PFS in a heavily pretreated population. A randomized phase II clinical trial in mRCC of this combination is ongoing.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Bevacizumab/administração & dosagem , Camptotecina/administração & dosagem , Carcinoma de Células Renais/tratamento farmacológico , Ciclodextrinas/administração & dosagem , Adulto , Idoso , Inibidores da Angiogênese/administração & dosagem , Inibidores da Angiogênese/efeitos adversos , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/química , Bevacizumab/efeitos adversos , Camptotecina/efeitos adversos , Carcinoma de Células Renais/patologia , Ciclodextrinas/efeitos adversos , Intervalo Livre de Doença , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/classificação , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nanopartículas/administração & dosagem , Nanopartículas/química , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos
3.
Phys Rev Lett ; 114(23): 236402, 2015 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-26196809

RESUMO

We demonstrate how to identify which physical processes dominate the low-energy spectral functions of correlated electron systems. We obtain an unambiguous classification through an analysis of the equation of motion for the electron self-energy in its charge, spin, and particle-particle representations. Our procedure is then employed to clarify the controversial physics responsible for the appearance of the pseudogap in correlated systems. We illustrate our method by examining the attractive and repulsive Hubbard model in two dimensions. In the latter, spin fluctuations are identified as the origin of the pseudogap, and we also explain why d-wave pairing fluctuations play a marginal role in suppressing the low-energy spectral weight, independent of their actual strength.

4.
Phys Rev Lett ; 110(24): 246405, 2013 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-25165946

RESUMO

Identifying the fingerprints of the Mott-Hubbard metal-insulator transition may be quite elusive in correlated metallic systems if the analysis is limited to the single particle level. However, our dynamical mean-field calculations demonstrate that the situation changes completely if the frequency dependence of the two-particle vertex functions is considered: The first nonperturbative precursors of the Mott physics are unambiguously identified well inside the metallic regime by the divergence of the local Bethe-Salpeter equation in the charge channel. In the low-temperature limit this occurs for interaction values where incoherent high-energy features emerge in the spectral function, while at high temperatures it is traceable up to the atomic limit.

5.
Phys Rev Lett ; 104(24): 246402, 2010 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-20867318

RESUMO

With an increasing complexity of nanoscopic systems and the modeling thereof, new theoretical tools are needed for a reliable calculation of complex systems with strong electronic correlations. To this end, we propose a new approach based on the recently introduced dynamical vertex approximation. We demonstrate its reliability already on the one-particle vertex (i.e., dynamical mean field theory) level by comparison with the exact solution. Modeling a quantum point contact with 110 atoms, we show that the contact becomes insulating already before entering the tunneling regime due to a local Mott-Hubbard transition occurring on the atoms which form the point contact.

6.
Nature ; 405(6790): 1027-30, 2000 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-10890437

RESUMO

The electrical resistivity, p, of a metal is usually interpreted in terms of the mean free path (the average distance, l, an electron travels before it is scattered). As the temperature is raised, the resistivity increases and the apparent mean free path is correspondingly reduced. In this semi-classical picture, the mean free path cannot be much shorter than the distance, d, between two atoms. This has been confirmed for many systems and was considered to be a universal behaviour. Recently, some apparent exceptions were found, including alkali-doped fullerenes and high-temperature superconductors. However, there remains the possibility that these systems are in exotic states, with only a small fraction of the conduction electrons contributing to the conductivity; the mean free path would then have to be correspondingly larger to explain the observed resistivity. Here we report a model calculation of electron conduction in alkali-doped fullerenes, in which the electrons are scattered by intramolecular vibrations. The resistivity at large temperatures implies l << d, demonstrating that there is no fundamental principle requiring l > or = d. At high temperatures, the semi-classical picture breaks down, and the electrons cannot be described as quasiparticles.

7.
J Intern Med ; 265(4): 488-95, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19019181

RESUMO

OBJECTIVES: The purpose of this study was to examine factors associated with high or low parathyroid hormone (PTH) levels in relationship to vitamin D insufficiency. DESIGN: This was a cross-sectional study consisting of 516 healthy men and women, aged 30-85, all Caucasians with vitamin D insufficiency [serum 25(OH)D<45 nmol L(-1)]. The group was divided into quartiles by PTH levels and the highest and lowest quartiles were compared with regard to various factors likely to affect calcium metabolism. We used stepwise multivariable logistic regression to determine the independent association between PTH levels and other variables for men and women separately. RESULTS: We found that men in the lowest PTH quartile were significantly younger, had less energy intake, lower body mass index (BMI) and better kidney function compared with the highest PTH quartile. They had also higher ionized calcium, insulin-like growth factor (IGF1) and testosterone and were more likely to smoke. Women within the lowest PTH quartile were younger, had lower BMI and magnesium values and higher IGF1 levels and were more likely to smoke. Stepwise multivariate regression showed that IGF1, testosterone and BMI were significantly associated with PTH in men (R(2)=0.472) but smoking, BMI and kidney function in women (R(2)=0.362). CONCLUSIONS: Our results indicate that during vitamin D insufficiency, factors other than calcium and vitamin D may modify PTH response. These factors may be different between sexes and we have identified novel factors, IGF1 and testosterone in men which may be compensatory in nature and confirmed previous factors such as smoking, BMI and kidney function in women.


Assuntos
Hormônio Paratireóideo/sangue , Deficiência de Vitamina D/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Cálcio/sangue , Estudos Transversais , Cistatina C/sangue , Dieta , Feminino , Humanos , Testes de Função Renal , Magnésio/sangue , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Fatores de Risco , Fatores Sexuais , Fumar , Testosterona/sangue , Vitamina D/sangue , Deficiência de Vitamina D/fisiopatologia
8.
Nature ; 455(7213): E6-7, 2008 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-18833217
9.
J Phys Condens Matter ; 28(4): 045501, 2016 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-26742570

RESUMO

We analyze self-energies of electrons away from the Fermi surface in doped Mott insulators using the dynamical cluster approximation to the Hubbard model. For large onsite repulsion, U, and hole doping, the magnitude of the self-energy for imaginary frequencies at the top of the band ([Formula: see text]) is enhanced with respect to the self-energy magnitude at the bottom of the band ([Formula: see text]). The self-energy behavior at these two [Formula: see text]-points is switched for electron doping. Although the hybridization is much larger for (0, 0) than for [Formula: see text], we demonstrate that this is not the origin of this difference. Isolated clusters under a downward shift of the chemical potential, [Formula: see text], at half-filling reproduce the overall self-energy behavior at (0, 0) and [Formula: see text] found in low hole doped embedded clusters. This happens although there is no change in the electronic structure of the isolated clusters. Our analysis shows that a downward shift of the chemical potential which weakly hole dopes the Mott insulator can lead to a large enhancement of the [Formula: see text] self-energy for imaginary frequencies which is not associated with electronic correlation effects, even in embedded clusters. Interpretations of the strength of electronic correlations based on self-energies for imaginary frequencies are, in general, misleading for states away from the Fermi surface.

10.
Phys Rev Lett ; 84(6): 1276-9, 2000 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-11017497

RESUMO

We study the influence of the lattice structure, the Jahn-Teller effect, and the Hund's rule coupling on a metal-insulator transition in A(n)C60 (A = K,Rb). The difference in the lattice structure favors A3C60 (fcc) being a metal and A4C60 (bct) being an insulator, and the coupling to H(g) Jahn-Teller phonons favors A4C60 being nonmagnetic. The coupling to H(g) ( A(g)) phonons decreases (increases) the value U(c) of the Coulomb integral at which the metal-insulator transition occurs. There is an important partial cancellation between the Jahn-Teller effect and the Hund's rule coupling.

11.
Geriatrics ; 52(5): 71-2, 77-80; quiz 81, 1997 May.
Artigo em Inglês | MEDLINE | ID: mdl-9152219

RESUMO

Moderate exercise for middle-aged and older adults is emerging as an important adjuvant to the treatment of many diseases. These include cardiovascular disease, diabetes, osteoporosis, osteoarthritis, insomnia, deconditioning, and (to a degree) obesity. A recent report from the United States Surgeon General recommends that most adults exercise most if not all days of the week, accumulating 180 minutes of moderate intensity exercise weekly. If your patients have been previously sedentary, encourage them to start a slow, stepwise exercise program. Ongoing support, encouragement, and follow-up can help them commit to and maintain a program of regular exercise.


Assuntos
Exercício Físico , Planejamento de Assistência ao Paciente , Idoso , Doença das Coronárias/prevenção & controle , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
12.
Eur J Drug Metab Pharmacokinet ; 8(4): 395-402, 1983.
Artigo em Inglês | MEDLINE | ID: mdl-6673977

RESUMO

The hydrolysis of estramustine phosphate by enzymes of blood, liver, intestines and prostate of man, dog and rat was studied by using specific analytical methods for the parent compound and some of its metabolites. Estramustine phosphate was stable in blood and plasma of different species but rapidly dephosphorylated to estramustine by liver, intestinal and prostatic enzymes. The prostate was the most active tissue. The ester bond by which nornitrogen mustard is linked to estradiol-17-phosphate was slowly cleaved by enzymes from the liver and prostate of the rat, dog and man. The dog tissues were more effective than those of the rat and man. Intestinal enzymes also exhibited the ability to hydrolyze the carbamic ester, but to a greater extent in the rat than in the dog. It is concluded that, with regard to the metabolism of estramustine, the rat is more similar to man than is the dog. Possible clinical implications of the biotransformation of estramustine phosphate are discussed.


Assuntos
Estramustina/metabolismo , Compostos de Mostarda Nitrogenada/metabolismo , Animais , Cães , Estramustina/sangue , Humanos , Hidrólise , Técnicas In Vitro , Mucosa Intestinal/metabolismo , Fígado/metabolismo , Masculino , Próstata/metabolismo , Ratos , Especificidade da Espécie
13.
J Phys Condens Matter ; 25(5): 052201, 2013 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-23264461

RESUMO

We analyze the origin of the pseudogap present in cuprate superconductors. We elucidate the mechanism of pseudogap formation close to the Mott localization within the dynamical cluster approach (DCA) to the Hubbard model. As the Coulomb interaction is increased, cluster-bath Kondo states are destroyed and a nondegenerate bound cluster state is formed, leading to a pseudogap. This occurs first at the antinodal point due to its weaker coupling to the bath, explaining the momentum dependence of the pseudogap. We find that the character of the pseudogap is related to breaking d-wave pairs.

14.
Phys Rev Lett ; 60(15): 1583, 1988 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-10038078
15.
Phys Rev Lett ; 69(6): 957-960, 1992 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-10047078
16.
Phys Rev Lett ; 56(18): 1968-1971, 1986 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-10032823
17.
Phys Rev Lett ; 65(9): 1148-1151, 1990 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-10043117
18.
Phys Rev Lett ; 55(1): 107-110, 1985 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-10031692
19.
Phys Rev Lett ; 74(16): 3221-3224, 1995 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-10058142
20.
Phys Rev Lett ; 70(8): 1180, 1993 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-10054307
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