Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 37
Filtrar
1.
Phys Rev Lett ; 121(22): 221301, 2018 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-30547645

RESUMO

We present results from an analysis of all data taken by the bicep2/Keck CMB polarization experiments up to and including the 2015 observing season. This includes the first Keck Array observations at 220 GHz and additional observations at 95 and 150 GHz. The Q and U maps reach depths of 5.2, 2.9, and 26 µK_{CMB} arcmin at 95, 150, and 220 GHz, respectively, over an effective area of ≈400 square degrees. The 220 GHz maps achieve a signal to noise on polarized dust emission approximately equal to that of Planck at 353 GHz. We take auto and cross spectra between these maps and publicly available WMAP and Planck maps at frequencies from 23 to 353 GHz. We evaluate the joint likelihood of the spectra versus a multicomponent model of lensed-ΛCDM+r+dust+synchrotron+noise. The foreground model has seven parameters, and we impose priors on some of these using external information from Planck and WMAP derived from larger regions of sky. The model is shown to be an adequate description of the data at the current noise levels. The likelihood analysis yields the constraint r_{0.05}<0.07 at 95% confidence, which tightens to r_{0.05}<0.06 in conjunction with Planck temperature measurements and other data. The lensing signal is detected at 8.8σ significance. Running a maximum likelihood search on simulations we obtain unbiased results and find that σ(r)=0.020. These are the strongest constraints to date on primordial gravitational waves.

2.
Phys Rev Lett ; 118(25): 251302, 2017 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-28696768

RESUMO

We present experimental constraints on the spin-dependent WIMP-nucleon elastic cross sections from the total 129.5 kg yr exposure acquired by the Large Underground Xenon experiment (LUX), operating at the Sanford Underground Research Facility in Lead, South Dakota (USA). A profile likelihood ratio analysis allows 90% C.L. upper limits to be set on the WIMP-neutron (WIMP-proton) cross section of σ_{n}=1.6×10^{-41} cm^{2} (σ_{p}=5×10^{-40} cm^{2}) at 35 GeV c^{-2}, almost a sixfold improvement over the previous LUX spin-dependent results. The spin-dependent WIMP-neutron limit is the most sensitive constraint to date.

3.
Phys Rev Lett ; 118(26): 261301, 2017 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-28707937

RESUMO

The first searches for axions and axionlike particles with the Large Underground Xenon experiment are presented. Under the assumption of an axioelectric interaction in xenon, the coupling constant between axions and electrons g_{Ae} is tested using data collected in 2013 with an exposure totaling 95 live days ×118 kg. A double-sided, profile likelihood ratio statistic test excludes g_{Ae} larger than 3.5×10^{-12} (90% C.L.) for solar axions. Assuming the Dine-Fischler-Srednicki-Zhitnitsky theoretical description, the upper limit in coupling corresponds to an upper limit on axion mass of 0.12 eV/c^{2}, while for the Kim-Shifman-Vainshtein-Zhakharov description masses above 36.6 eV/c^{2} are excluded. For galactic axionlike particles, values of g_{Ae} larger than 4.2×10^{-13} are excluded for particle masses in the range 1-16 keV/c^{2}. These are the most stringent constraints to date for these interactions.

4.
Phys Rev Lett ; 118(2): 021303, 2017 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-28128598

RESUMO

We report constraints on spin-independent weakly interacting massive particle (WIMP)-nucleon scattering using a 3.35×10^{4} kg day exposure of the Large Underground Xenon (LUX) experiment. A dual-phase xenon time projection chamber with 250 kg of active mass is operated at the Sanford Underground Research Facility under Lead, South Dakota (USA). With roughly fourfold improvement in sensitivity for high WIMP masses relative to our previous results, this search yields no evidence of WIMP nuclear recoils. At a WIMP mass of 50 GeV c^{-2}, WIMP-nucleon spin-independent cross sections above 2.2×10^{-46} cm^{2} are excluded at the 90% confidence level. When combined with the previously reported LUX exposure, this exclusion strengthens to 1.1×10^{-46} cm^{2} at 50 GeV c^{-2}.

5.
Phys Rev Lett ; 116(16): 161301, 2016 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-27152785

RESUMO

We present constraints on weakly interacting massive particles (WIMP)-nucleus scattering from the 2013 data of the Large Underground Xenon dark matter experiment, including 1.4×10^{4} kg day of search exposure. This new analysis incorporates several advances: single-photon calibration at the scintillation wavelength, improved event-reconstruction algorithms, a revised background model including events originating on the detector walls in an enlarged fiducial volume, and new calibrations from decays of an injected tritium ß source and from kinematically constrained nuclear recoils down to 1.1 keV. Sensitivity, especially to low-mass WIMPs, is enhanced compared to our previous results which modeled the signal only above a 3 keV minimum energy. Under standard dark matter halo assumptions and in the mass range above 4 GeV c^{-2}, these new results give the most stringent direct limits on the spin-independent WIMP-nucleon cross section. The 90% C.L. upper limit has a minimum of 0.6 zb at 33 GeV c^{-2} WIMP mass.

6.
Phys Rev Lett ; 116(16): 161302, 2016 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-27152786

RESUMO

We present experimental constraints on the spin-dependent WIMP (weakly interacting massive particle)-nucleon elastic cross sections from LUX data acquired in 2013. LUX is a dual-phase xenon time projection chamber operating at the Sanford Underground Research Facility (Lead, South Dakota), which is designed to observe the recoil signature of galactic WIMPs scattering from xenon nuclei. A profile likelihood ratio analysis of 1.4×10^{4} kg day of fiducial exposure allows 90% C.L. upper limits to be set on the WIMP-neutron (WIMP-proton) cross section of σ_{n}=9.4×10^{-41} cm^{2} (σ_{p}=2.9×10^{-39} cm^{2}) at 33 GeV/c^{2}. The spin-dependent WIMP-neutron limit is the most sensitive constraint to date.

7.
Phys Rev Lett ; 112(9): 091303, 2014 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-24655239

RESUMO

The Large Underground Xenon (LUX) experiment is a dual-phase xenon time-projection chamber operating at the Sanford Underground Research Facility (Lead, South Dakota). The LUX cryostat was filled for the first time in the underground laboratory in February 2013. We report results of the first WIMP search data set, taken during the period from April to August 2013, presenting the analysis of 85.3 live days of data with a fiducial volume of 118 kg. A profile-likelihood analysis technique shows our data to be consistent with the background-only hypothesis, allowing 90% confidence limits to be set on spin-independent WIMP-nucleon elastic scattering with a minimum upper limit on the cross section of 7.6 × 10(-46) cm(2) at a WIMP mass of 33 GeV/c(2). We find that the LUX data are in disagreement with low-mass WIMP signal interpretations of the results from several recent direct detection experiments.

8.
Science ; 293(5536): 1806-11, 2001 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-11546867

RESUMO

Recently we reported that antibodies can generate hydrogen peroxide (H2O2) from singlet molecular oxygen (1O2*). We now show that this process is catalytic, and we identify the electron source for a quasi-unlimited generation of H2O2. Antibodies produce up to 500 mole equivalents of H2O2 from 1O2*, without a reduction in rate, and we have excluded metals or Cl- as the electron source. On the basis of isotope incorporation experiments and kinetic data, we propose that antibodies use H2O as an electron source, facilitating its addition to 1O2* to form H2O3 as the first intermediate in a reaction cascade that eventually leads to H2O2. X-ray crystallographic studies with xenon point to putative conserved oxygen binding sites within the antibody fold where this chemistry could be initiated. Our findings suggest a protective function of immunoglobulins against 1O2* and raise the question of whether the need to detoxify 1O2* has played a decisive role in the evolution of the immunoglobulin fold.


Assuntos
Anticorpos Catalíticos/metabolismo , Peróxido de Hidrogênio/metabolismo , Oxidantes/metabolismo , Oxigênio/metabolismo , Água/química , Água/metabolismo , Animais , Anticorpos Catalíticos/química , Sítios de Ligação , Catálise , Sequência Conservada , Cristalografia por Raios X , Humanos , Cinética , Modelos Moleculares , Oxidantes/química , Oxirredução , Conformação Proteica , Oxigênio Singlete , Espectrometria de Massas por Ionização por Electrospray , Termodinâmica , Triptofano/metabolismo , Raios Ultravioleta , Xenônio/metabolismo
9.
Sci Rep ; 7(1): 11030, 2017 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-28887473

RESUMO

We demonstrate on-chip, differential DNA and RNA extraction from a single cell using a microfluidic chip and a two-stage lysis protocol. This method enables direct use of the whole extract, without additional washing steps, reducing sample loss. Using this method, the tumor driving pathway in individual cells from a colorectal cancer cell line was determined by applying a Bayesian computational pathway model to sequences obtained from the RNA fraction of a single cell and, the mutations driving the pathway were determined by analyzing sequences obtained from the DNA fraction of the same single cell. This combined functional and mutational pathway assessment of a single cell could be of significant value for dissecting cellular heterogeneity in tumors and analyzing single circulating tumor cells.


Assuntos
DNA/isolamento & purificação , Redes Reguladoras de Genes , Microfluídica/métodos , RNA/isolamento & purificação , Análise de Célula Única/métodos , Linhagem Celular Tumoral , Neoplasias Colorretais/patologia , Misturas Complexas/análise , Misturas Complexas/isolamento & purificação , DNA/análise , Humanos , RNA/análise
10.
J Mol Biol ; 314(1): 93-102, 2001 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-11724535

RESUMO

Murine antibody 1D4 selectively catalyzes a highly disfavored beta-elimination reaction. Crystal structures of unliganded 1D4 and 1D4 in complex with a transition-state analog (TSA) have elucidated a possible general base mode of catalysis. The structures of the unliganded and liganded Fabs were determined to 1.80 and 1.85 A resolution, respectively. The structure of the complex reveals a binding pocket with high shape complementarity to the TSA, which is recruited to coerce the substrate into the sterically demanding, eclipsed conformation that is required for catalysis. A histidine residue and two water molecules are likely involved in the catalysis. The structure supports either a concerted E2 or stepwise E1cB-like mechanism for elimination. Finally, the liganded 1D4 structure shows minor conformational rearrangements in CDR H2, indicative of induced-fit binding of the hapten. 1D4 has pushed the boundaries of antibody-mediated catalysis into the realm of disfavored reactions and, hence, represents an important milestone in the development of this technology.


Assuntos
Anticorpos Catalíticos/química , Anticorpos Catalíticos/metabolismo , Fragmentos Fab das Imunoglobulinas/química , Fragmentos Fab das Imunoglobulinas/metabolismo , Animais , Anticorpos Catalíticos/imunologia , Sítios de Ligação de Anticorpos , Catálise , Cátions/metabolismo , Cristalografia por Raios X , Entropia , Haptenos/química , Haptenos/imunologia , Haptenos/metabolismo , Ligação de Hidrogênio , Fragmentos Fab das Imunoglobulinas/imunologia , Imunoglobulina G/química , Imunoglobulina G/imunologia , Imunoglobulina G/metabolismo , Ligantes , Camundongos , Modelos Moleculares , Conformação Proteica , Solventes , Eletricidade Estática , Relação Estrutura-Atividade
11.
J Mol Biol ; 311(1): 9-15, 2001 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-11469854

RESUMO

Murine monoclonal antibody GNC92H2 was elicited by active immunization with a cocaine immunoconjugate and binds free cocaine with excellent specificity and moderate affinity. Improvement of affinity, as well as humanization of GNC92H2, would be advantageous in immunopharmacotherapy for cocaine addiction, and for emergency cases of drug overdose. Toward this end, the crystal structure of an engineered murine-human chimeric Fab of GNC92H2 complexed with cocaine was determined at 2.3 A resolution. Structural analysis reveals a binding pocket with high shape and charge complementarity to the cocaine framework, which explains the specificity for cocaine, as opposed to the pharmacologically inactive cocaine metabolites. Importantly, the structure provides a foundation for mutagenesis to enhance the binding affinity for cocaine and potent cocaine derivatives, such as cocaethylene, and for additional humanization of the antibody.


Assuntos
Anticorpos Monoclonais/química , Anticorpos Monoclonais/imunologia , Especificidade de Anticorpos/imunologia , Cocaína/imunologia , Animais , Anticorpos Monoclonais/genética , Sítios de Ligação de Anticorpos/imunologia , Cátions/metabolismo , Cocaína/análogos & derivados , Cocaína/metabolismo , Cristalografia por Raios X , Desenho de Fármacos , Humanos , Ligação de Hidrogênio , Fragmentos Fab das Imunoglobulinas/química , Fragmentos Fab das Imunoglobulinas/genética , Fragmentos Fab das Imunoglobulinas/imunologia , Imunoterapia , Camundongos , Modelos Moleculares , Conformação Proteica , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/imunologia , Eletricidade Estática
12.
J Neurol Sci ; 42(3): 407-16, 1979 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-512674

RESUMO

The concentrations of arsenic, manganese and selenium per gram wet tissue weight were determined in samples from 24 areas of normal human brain from 5 persons with ages ranging from 15 to 81 years of age. The concentrations of the 3 elements were determined for each sample by means of neutron activation analysis with radiochemical separation. Distinct patterns of distribution were shown for each of the 3 elements. Variations between individuals were found for some but not all brain areas, resulting in coefficients of variation between individuals of about 30% for arsenic, 10% for manganese and 20% for selenium. The results seem to indicate that arsenic is associated with the lipid phase, manganese with the dry matter and selenium with the aqueous phase of brain tissue.


Assuntos
Arsênio/análise , Química Encefálica , Manganês/análise , Selênio/análise , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Ativação de Nêutrons
13.
J Neurol Sci ; 51(3): 437-46, 1981 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-7276987

RESUMO

The concentrations of arsenic, manganese and selenium/g wet tissue weight were determined in samples from 24 areas of the human brain from 3 patients with chronic renal insufficiency, 2 with Parkinson's disease and 1 with amyotrophic lateral sclerosis. The concentrations of the 3 elements were determined for each sample by neutron activation analysis with radiochemical separation. Overall arsenic concentrations were about 2.5 times higher in patients with chronic renal failure than in controls, and lower than normal in the patients with Parkinson's disease and amyotrophic lateral sclerosis. There were no obvious differences in the overall concentrations of manganese and selenium from one group to another. Even multivariate data analysis by the SIMCA method failed to reveal any significant difference in the distribution pattern of manganese and selenium in Parkinson's disease compared to normal controls.


Assuntos
Esclerose Lateral Amiotrófica/metabolismo , Arsênio/metabolismo , Encéfalo/metabolismo , Falência Renal Crônica/metabolismo , Manganês/metabolismo , Doença de Parkinson/metabolismo , Selênio/metabolismo , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA