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A key challenge in realizing practical quantum networks for long-distance quantum communication involves robust entanglement between quantum memory nodes connected by fibre optical infrastructure1-3. Here we demonstrate a two-node quantum network composed of multi-qubit registers based on silicon-vacancy (SiV) centres in nanophotonic diamond cavities integrated with a telecommunication fibre network. Remote entanglement is generated by the cavity-enhanced interactions between the electron spin qubits of the SiVs and optical photons. Serial, heralded spin-photon entangling gate operations with time-bin qubits are used for robust entanglement of separated nodes. Long-lived nuclear spin qubits are used to provide second-long entanglement storage and integrated error detection. By integrating efficient bidirectional quantum frequency conversion of photonic communication qubits to telecommunication frequencies (1,350 nm), we demonstrate the entanglement of two nuclear spin memories through 40 km spools of low-loss fibre and a 35-km long fibre loop deployed in the Boston area urban environment, representing an enabling step towards practical quantum repeaters and large-scale quantum networks.
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A multi-frame, X-ray diffraction (XRD) detector system has been developed for use in time-resolved XRD measurements during single-event experiments at the Dynamic Compression Sector (DCS) at the Advanced Photon Source (APS). The system is capable of collecting four sequential XRD patterns separated by 153â ns, the period of the APS storage ring in the 24-bunch mode. This capability allows an examination of the temporal evolution of material dynamics in single-event experiments, such as plate impact experiments, explosive detonations, and split-Hopkinson pressure bar experiments. This system is available for all user experiments at the DCS. Here, the system description and measured performance parameters (detective quantum efficiency, spatial and temporal resolution, and dynamic range) are presented along with procedures for synchronization and image post-processing.
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We characterize the 795 nm ^{3}H_{6} to ^{3}H_{4} transition of Tm^{3+} in a Ti^{4+}:LiNbO_{3} waveguide at temperatures as low as 800 mK. Coherence and hyperfine population lifetimes-up to 117 µs and 2.5 h, respectively-exceed those at 3 K at least tenfold, and are equivalent to those observed in a bulk Tm^{3+}:LiNbO_{3} crystal under similar conditions. We also find a transition dipole moment that is equivalent to that of the bulk. Finally, we prepare a 0.5 GHz-bandwidth atomic frequency comb of finesse >2 on a vanishing background. These results demonstrate the suitability of rare-earth-ion-doped waveguides created using industry-standard Ti indiffusion in LiNbO_{3} for on-chip quantum applications.
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The experimental determination of atomistic mechanisms linking crystal structures during a compression-driven solid-solid phase transformation is a long-standing and challenging scientific objective. Using new capabilities at the Dynamic Compression Sector at the Advanced Photon Source, the structure of shocked Si at 19 GPa was identified as simple hexagonal, and the lattice orientations between ambient cubic diamond and simple hexagonal structures were related. The approach is general and provides a powerful new method for examining atomistic mechanisms during stress-induced structural changes.
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We investigate the relevant spectroscopic properties of the 795 nm (3)H(6)â(3)H(4) transition in 1% Tm(3+):Y(3)Ga(5)O(12) at temperatures as low as 1.2 K for optical quantum memories based on persistent spectral tailoring of narrow absorption features. Our measurements reveal that this transition has uniform coherence properties over a 56 GHz bandwidth, and a simple hyperfine structure split by ± 44 MHz/T with lifetimes of up to hours. Furthermore, we find a (3)F(4) population lifetime of 64 ms-one of the longest lifetimes observed for an electronic level in a solid--and an exceptionally long coherence lifetime of 490 µs--the longest ever observed for optical transitions of Tm(3+) ions in a crystal. Our results suggest that this material allows realizing broadband quantum memories that enable spectrally multiplexed quantum repeaters.
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BACKGROUND: Melanoma and basal cell carcinoma (BCC) affect similar body sites and share a complex relationship with sun exposure. OBJECTIVE: To establish the existence and magnitude of association between melanocytic naevi, the strongest predictors of melanoma, and BCC to give possible insights into shared pathways of solar ultraviolet tumourigenesis. METHODS: In a community-based longitudinal Australian study, detailed information was collected about sun sensitivity, and dermatologists assessed skin colour and counted naevi on the forearms (1986) and back (1992). The BCC frequency and sites were prospectively monitored until 2007. Multivariate logistic regression was used to assess the association of naevi on the forearms or on the back with the development of BCC, adjusting for other risk factors. RESULTS: Of 1621 study participants in 1992, 1339 (average age 49) had complete follow-up and 401 (30%) of these had 1202 histologically confirmed BCCs until 2007. After adjustment for age, gender, skin colour, naevi on the back and sun exposure, overall BCC risk increased significantly in those with forearm naevi (odds ratio: 1.5; 95% confidence intervals: 1.1-1.9). Risk of BCC specifically on the back was doubled in those with many (11 or more) forearm naevi compared with no forearm naevi (odds ratio: 2.4; 95% confidence interval: 1.1-4.8). Naevi on the back were not associated with subsequent basal cell carcinoma. CONCLUSIONS: High naevus prevalence on the arms is associated with future BCC development.
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Carcinoma Basocelular/complicações , Nevo Pigmentado/complicações , Adulto , Austrália , Carcinoma Basocelular/etiologia , Carcinoma Basocelular/patologia , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Neoplasias Induzidas por Radiação/complicações , Neoplasias Induzidas por Radiação/patologia , Nevo Pigmentado/etiologia , Nevo Pigmentado/patologiaAssuntos
Interleucinas/genética , Mutação de Sentido Incorreto/genética , Psoríase/genética , Adulto , Idade de Início , Análise Mutacional de DNA , Feminino , Heterozigoto , Humanos , Interleucinas/química , Doenças da Boca/genética , Mucosa Bucal , Fenótipo , Estrutura Terciária de Proteína/genética , Gêmeos MonozigóticosRESUMO
The injection of 60 micrograms of 9,10-dimethyl-1,2-benzanthracene into newborn mice gave rise to a very high incidence of malignant thymomas. The tumor incidence was directly related to the dose of the carcinogen. The neonatal injection of the carcinogen also resulted in a depression in the immune response when the animals were challenged with an antigert as early as 4 weeks or as late as 11 weeks after administration of the carcinogen.
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OBJECTIVES: To confirm the feasibility of nurse practitioner interventionin non-high-risk patients with recent myocardial infarction (MI). DESIGN: Observational study. SETTING: Acute coronary care unit in a teaching hospital. METHODS: We performed an open-label feasibility study to identify non-high-risk MI patients and evaluate the outcome of a new nurse practitioner intervention programme. The initial pilot phase served to identify the non-high-risk population. In the subsequent confirmation phase, 500 consecutive non-high-risk post-MI patients with preserved LV function without heart failure were included to receive nurse practitioner management. The nurse practitioner intervention started on transfer from the coronary care unit to the cardiology ward and continued thereafter for up to 30 days. MAIN OUTCOME MEASURES: Time to first event analysis of death from all causes or repeat myocardial infarction. RESULTS: 500 Patients without signs of heart failure or depressed LV function were identified as nonhigh- risk and eligible for inclusion in the nurse practitioner intervention programme. In the implementation phase, none of the patients died and 0.9% developed a repeat myocardial infarction after 30 days of follow-up. Compared with the pilot phase, patients in the implementation phase spent fewer days in hospital (mean 11.1 versus 6.2 days; p<0.001). CONCLUSION: It is feasible to identify non-high-risk post-MI patients, who can be managed adequately by a nurse practitioner. Embedding experienced nurse practitioners within critical care pathways may result in significant decreases in length of hospital stay. (Neth Heart J 2009;17:61-7.Neth Heart J 2009;17:61-7.).
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Transit through the carbon liquid phase has significant consequences for the subsequent formation of solid nanocarbon detonation products. We report dynamic measurements of liquid carbon condensation and solidification into nano-onions over â½200 ns by analysis of time-resolved, small-angle X-ray scattering data acquired during detonation of a hydrogen-free explosive, DNTF (3,4-bis(3-nitrofurazan-4-yl)furoxan). Further, thermochemical modeling predicts a direct liquid to solid graphite phase transition for DNTF products ~200 ns post-detonation. Solid detonation products were collected and characterized by high-resolution electron microscopy to confirm the abundance of carbon nano-onions with an average diameter of â½10 nm, matching the dynamic measurements. We analyze other carbon-rich explosives by similar methods to systematically explore different regions of the carbon phase diagram traversed during detonation. Our results suggest a potential pathway to the efficient production of carbon nano-onions, while offering insight into the phase transformation kinetics of liquid carbon under extreme pressures and temperatures.
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There are both fundamental and practical motivations for studying whether quantum entanglement can exist in macroscopic systems. However, multiparty entanglement is generally fragile and difficult to quantify. Dicke states are multiparty entangled states where a single excitation is delocalized over many systems. Building on previous work on quantum memories for photons, we create a Dicke state in a solid by storing a single photon in a crystal that contains many large atomic ensembles with distinct resonance frequencies. The photon is re-emitted at a well-defined time due to an interference effect analogous to multi-slit diffraction. We derive a lower bound for the number of entangled ensembles based on the contrast of the interference and the single-photon character of the input, and we experimentally demonstrate entanglement between over two hundred ensembles, each containing a billion atoms. We also illustrate the fact that each individual ensemble contains further entanglement.Multipartite entanglement is of both fundamental and practical interest, but is notoriously difficult to witness and characterise. Here, Zarkeshian et al. demonstrate multipartite entanglement in an atomic frequency comb storing a single photon in a Dicke state spread over a macroscopic ensemble.
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Non-destructive detection of photonic qubits is an enabling technology for quantum information processing and quantum communication. For practical applications, such as quantum repeaters and networks, it is desirable to implement such detection in a way that allows some form of multiplexing as well as easy integration with other components such as solid-state quantum memories. Here, we propose an approach to non-destructive photonic qubit detection that promises to have all the mentioned features. Mediated by an impurity-doped crystal, a signal photon in an arbitrary time-bin qubit state modulates the phase of an intense probe pulse that is stored during the interaction. Using a thulium-doped waveguide in LiNbO3, we perform a proof-of-principle experiment with macroscopic signal pulses, demonstrating the expected cross-phase modulation as well as the ability to preserve the coherence between temporal modes. Our findings open the path to a new key component of quantum photonics based on rare-earth-ion-doped crystals.
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Immunoreceptor tyrosine-based inhibitory motifs (ITIMs) have the restricted consensus sequence V/I/xYxxL/V, but may be more broadly defined by the sequence V/I/L/SxYxxL/V/I/S. If one includes the ITIM of CTLA-4, then the sequence becomes psixYxxpsi, where psi represents amino acids with nonpolar side chains. Aside from their presence in various inhibitory molecules, ITIMs are also found on many activating receptors and pathways. ITIMs with the restricted consensus sequence occur on IL-4Ralpha, IL-3Rbeta type II, gp130 cytokineR, OB-R (leptinR), LIF-Rbeta TNF-RI, G-CSF-R, PDGF-R, Blk, Ctk/Ntk, Lsk, Zap-70, PKB/RACalpha, PKC-alpha, PKC-beta, PKC-gamma, PKC-delta, PKC-zeta, PKC-epsilon, PKC-eta, PKC-phi, PKC-mu, calmodulin-dependent kinase IIdelta, SLP-76-associated protein, FYN-binding protein, Shc binding protein, RasGRF2, CDC25 homologue, Jak2, Jak3, PLCbeta1, and PLCbeta3. If ITIMs are defined by a broader consensus sequence, the list of ITIMs on activating molecules becomes even larger. In some instances, these ITIMs have been shown to associate with inhibitory phosphatases. Whether these ITIMs on activating receptors/pathways are necessary and sufficient for negative control of activating events and for immunologic tolerance is not yet known. In some instances, ITIMs on coinhibitory receptors are also required for appropriate negative regulation. By studying events leading to negative control during activation and to immunologic tolerance, it should be possible to discern the balance between antigen receptor-based negative events and coinhibition.
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Motivos de Aminoácidos , Tolerância Imunológica , Receptores de Antígenos/metabolismo , Receptores Imunológicos/metabolismo , Tirosina , Sequência Consenso , Proteínas Tirosina Quinases , Receptores de Citocinas , Transdução de SinaisRESUMO
The tripartite inactivation model proposed that coaggregation of the B cell antigen receptor (BCR) with the Fc receptor (FcR) by antigen and specific IgG antibody complexes explained the Fc-dependent inhibition of immune responses by antibody. This model has since been substantiated by many observations and its impact on studies of immune regulation has been threefold: (1) IgG antibody, via Fc gamma RIIB, mediates inhibition of cell activation in many cell types, demonstrating the general importance of this mechanism in immune regulation; (2) Fc gamma RIIB was the first receptor described that regulates immune responses by coinhibition, that is, regulation as a result of interaction between activating receptors (BCR, TCR, Fc epsilon RI, Fc gamma RIII, Fc gamma RIIA) and inhibitory receptors (Fc gamma RIIB, CTLA4, CD5, CD22, p58/70/140 KIR, gp49B1/gp91, Ly49A/C/E/F/G, NKG2-A/B, APCR, Fas (CD95), TGF beta-R, TNF-R, IFN gamma-R, and others). The list of coinhibitors is expanding, just as the list of costimulators has grown. Tolerance through multiple coinhibitors implies that Signal 1 alone is not tolerogenic; and (3) Studies of Fc gamma RIIB coinhibitory mechanisms have pointed the way to potential general inhibitory signaling pathways used by many receptors, involving the competing effects of various kinases and phosphatases, and other competitive events. Investigations of Fc gamma RIIB physiologic function and of other coinhibitory receptors, together with recent biochemical analyses, give an initial understanding of the biology of these inhibitory receptory receptors. Paradoxes within and between theoretical constructs, functional observations, and mechanistic studies point to critical questions for future study.
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Tolerância Imunológica , Ativação Linfocitária , Receptores de Antígenos/imunologia , Receptores Fc/imunologia , Animais , Sequência Consenso , Capeamento Imunológico , Camundongos , Camundongos Knockout , Modelos Imunológicos , Peptídeos , Transdução de SinaisRESUMO
Different biochemical and cytochemical techniques were applied to characterize the sites of localization of thrombospondin in cultured endothelial cells. The results obtained by [35S]methionine labeling, immunoblotting, immunoprecipitation, fluorescence microscopy, ultracytochemistry, immunogold labeling, and silver enhancement experiments revealed that thrombospondin secreted by endothelial cells is structurally organized together with proteoheparan sulfate in spherical granules at the cell surface. These granules are about 100 to 300 nm in size. Heparin or enzymatic degradation with heparitinase, but not with ABC lyase, release thrombospondin from the cell surface. Fibronectin is expressed in the extracellular matrix of endothelial cells in a fibrillar organization, clearly distinct from the punctate pattern of thrombospondin on the cell surface. Furthermore, secreted thrombospondin is highly enriched together with fibronectin and proteoheparan sulfate in cell attachment sites and in cell migration tracks. In cell migration tracks proteoheparan sulfate more clearly resembles the fibrillar distribution pattern of fibronectin, whereas thrombospondin reveals a rather monodisperse pattern. The obtained data suggest preferential sites of interaction between thrombospondin and heparan sulfate proteoglycans on the cell surface and a participation of thrombospondin in cell adhesion and cell migration.
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Endotélio Vascular/citologia , Glicoproteínas/metabolismo , Glicoproteínas de Membrana/metabolismo , Animais , Aorta/citologia , Adesão Celular , Movimento Celular , Células Cultivadas , Proteoglicanas de Sulfatos de Condroitina/metabolismo , Endotélio Vascular/metabolismo , Matriz Extracelular/análise , Matriz Extracelular/metabolismo , Matriz Extracelular/ultraestrutura , Fibronectinas/metabolismo , Glicoproteínas/análise , Glicoproteínas/imunologia , Glicosaminoglicanos/metabolismo , Proteoglicanas de Heparan Sulfato , Heparina/farmacologia , Heparitina Sulfato/metabolismo , Histocitoquímica , Humanos , Immunoblotting , Microscopia Eletrônica , Polissacarídeo-Liases/metabolismo , Testes de Precipitina , Suínos , TrombospondinasRESUMO
Exposure to tobacco smoke is measured by a variety of invasive and noninvasive techniques. Our purpose was to examine how well some of these measures correlated when obtained simultaneously from the same subjects. On three occasions, six subjects were studied while they were smoking a single cigarette after 24 hr of abstinence. There were positive correlations between increases in heart rate and plasma nicotine concentrations and between percentage carboxyhemoglobin and exhaled carbon monoxide. Although residual cotinine was readily detected in samples of plasma before the subjects smoked, there was an increase in mean levels, with a peak approximately 1 hr after smoking. Urinary concentrations of nicotine, cotinine, and nicotine-1'-N-oxide and thiocyanate levels in plasma and saliva were essentially unchanged by smoking a single cigarette. Data on smoke generation and nicotine retention in cigarette butts correlated poorly with all other measures of smoke uptake.
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Nicotina/metabolismo , Fumar , Adulto , Monóxido de Carbono/análise , Carboxihemoglobina/análise , Cromatografia Gasosa , Cotinina/sangue , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Masculino , Nicotina/sangue , Nicotina/farmacologia , Tiocianatos/sangueRESUMO
Continuous blockade of B-cell antigen receptors (BCRs) with Fab alpha sIg prevents the anti-ssDNA response of high, but not low, density B cells. Signaling via the BCRs, by prior exposure to crosslinking F(ab')2 alpha sIg, had no effect on the spontaneous anti-DNA response, but prevented a lipopolysaccharide-induced anti-DNA response. Pretreatment with intact alpha sIg, which provides exogenously derived Fc signals, reduced the response. An Fc-signal-blocking agent, F(ab')2 anti-IgG-Fc antibody, increased the number of anti-DNA antibody-forming cells produced in the absence of exogenous IgG anti-ssDNA antibody. Thus, activation is dependent on the availability of the BCRs, prior BCR crosslinking does not interfere with activation, and endogenous IgG anti-ssDNA antibody limits the activation of anti-ssDNA-specific B cells most of which are T-cell independent. These results indicate that the anti-ssDNA response is driven through the BCR.
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Anticorpos Antinucleares/biossíntese , DNA de Cadeia Simples/imunologia , Receptores de Antígenos de Linfócitos B/imunologia , Animais , Células Cultivadas , Ensaio de Imunoadsorção Enzimática , Eritrócitos/imunologia , Fragmentos Fab das Imunoglobulinas , Lipopolissacarídeos/imunologia , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos CBA , Camundongos Endogâmicos DBA , Receptores Fc , Ovinos/imunologia , Transdução de SinaisRESUMO
Ligation of surface immunoglobulin on resting or activated nonautoimmune B cells inhibited lipopolysaccharide (LPS)-induced total IgM production. B cells from NZB, (NZB x NZW)F1, and BXSB mice were relatively resistant, but B cells from NZW or MRL/lpr mice were inhibited. The resistance occurs in B cells from young and old NZB mice, and in both resting and activated splenic NZB B cells. Anti-ssDNA responses induced by lipopolysaccharide occur in the presence of antigen-receptor-ligating antibody in NZB, but not in DBA/2, B cells. Antagonism in signaling between the antigen and LPS receptor is not a general B cell hyporesponsiveness, but defects in antagonism specifically between antigen and LPS signaling may be a predisposing factor to autoimmune disease in some autoimmune strains of mice.
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Autoimunidade/imunologia , Linfócitos B/imunologia , Imunoglobulina M/biossíntese , Receptores de Antígenos de Linfócitos B/metabolismo , Animais , Linfócitos B/efeitos dos fármacos , Células Cultivadas , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Lipopolissacarídeos/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos , Camundongos MutantesRESUMO
The short-term kinetics of T cell-mediated cytotoxicity was investigated using a cloning inhibition assay. Murine cytotoxic thymus-derived lymphocytes (CTL) generated in vitro in mixed leukocyte cultures (MLC), were incubated for various periods of time at 37 degrees C with allogeneic mastocytoma target cells. The mixtures were then plated in soft agar, and mastocytoma clone formation was assessed after 5-7 days incubation. Using this technique, it was demonstrated that events leading to the loss of cloning ability could be detected after 1-3 min incubation at 37 degrees C, and after 20-30 min, 95% of the clone forming cells had been inactivated. When these results were compared directly with those obtained using the conventional 51Cr-release assay, it was found that the events leading to loss of cloning ability occurred more rapidly than indicated by the isotope assay. However, a modification of the 51Cr-release assay involving EDTA addition, gave comparable results to the cloning inhibition assay. These results raise the possibility that the events leading to 51Cr-release of tumor target cells may be related in time to those leading to the loss of cloning ability.
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Linfócitos T/imunologia , Animais , Radioisótopos de Cromo , Células Clonais/imunologia , Testes Imunológicos de Citotoxicidade , Relação Dose-Resposta Imunológica , Ácido Edético/metabolismo , Cinética , Sarcoma de Mastócitos/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBARESUMO
The effect of cyclosporine (CsA) on the in vivo cell-mediated immune response to donor antigens was examined sequentially following cadaveric renal transplantation in both immunologically naive and specifically sensitized allograft recipients. Cytotoxic T lymphocytes (CTL) exhibiting preferential specificity for donor antigens were detected in the peripheral blood of all patients receiving azathioprine (AZA) immunosuppression by two weeks posttransplant, disappearing progressively over the first three months with clinical quiescence. In contrast, the generation of donor-reactive CTL was significantly diminished in incidence (P = 0.05) and in magnitude (P = 0.004) in subjects receiving CsA. CTL were detected in only 36% of patients by two weeks posttransplant, and were not detectable in any CsA-treated patient after the sixth posttransplant week. The ability of CsA to inhibit clonal reexpansion of CTL was examined both in vitro and in vivo in subjects exhibiting prior sensitization to donor antigens. In vitro, CsA caused a dose-dependent inhibition of accelerated (72-hr MLC) CTL generation following restimulation with donor spleen cells, which was quantitatively identical to that in parallel cultures using responder PBL from non-sensitized individuals. In vivo, CsA produced a rapid disappearance of circulating CTL posttransplant in patients who exhibited specific cell-mediated sensitization to the graft donor, as evidenced by the presence of circulating donor-reactive CTL prior to transplantation. In contrast, in patients receiving AZA there was a rapid increase in donor-reactive CTL in the peripheral blood following transplantation. CTL persisted for six weeks or longer, and two of four patients lost the graft to irreversible acute rejection within the first four weeks.