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1.
Phys Rev Lett ; 131(11): 117001, 2023 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-37774257

RESUMEN

Josephson junctions in InAs nanowires proximitized with an Al shell can host gate-tunable Andreev bound states. Depending on the bound state occupation, the fermion parity of the junction can be even or odd. Coherent control of Andreev bound states has recently been achieved within each parity sector, but it is impeded by incoherent parity switches due to excess quasiparticles in the superconducting environment. Here, we show that we can polarize the fermion parity dynamically using microwave pulses by embedding the junction in a superconducting LC resonator. We demonstrate polarization up to 94%±1% (89%±1%) for the even (odd) parity as verified by single shot parity readout. Finally, we apply this scheme to probe the flux-dependent transition spectrum of the even or odd parity sector selectively, without any postprocessing or heralding.

2.
Tech Coloproctol ; 27(11): 979-993, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37632643

RESUMEN

PURPOSE: Complete mesocolic excision improves lymphadenectomy for right hemicolectomy and respects the embryological planes. However, its effect on cancer-free and overall survival is questioned. Therefore, we aimed to determine the potential benefits of the technique by performing a systematic review of the literature and meta-analysis of the available evidence. METHODS: Web of Science, PubMed/Medline, and Embase were searched on February 22, 2023. Original studies on short- and long-term oncological outcomes of adult patients undergoing right hemicolectomy with complete mesocolic excision as a treatment for primary colon cancer were considered for inclusion. Outcomes were extracted and pooled using a model with random effects. RESULTS: A total of 586 publications were identified through database searching, and 18 from citation searching. Exclusion of 552 articles left 24 articles for inclusion. Meta-analysis showed that complete mesocolic excision increased the lymph node harvest (5 studies, 1479 patients, MD 9.62, 95% CI 5.83-13.41, p > 0.0001, I2 84%), 5-year overall survival (5 studies, 2381 patients, OR 1.88, 95% CI 1.14-3.09, p = 0.01, I2 66%), 5-year disease-free survival (4 studies, 1376 patients, OR 2.21, 95% CI 1.51-3.23, p < 0.0001, I2 0%) and decreased the incidence of local recurrence (4 studies, 818 patients, OR 0.27, 95% CI 0.09-0.79, p = 0.02, I2 0%) when compared to standard right hemicolectomy. Perioperative morbidity was similar between the techniques (8 studies, 3899 patients, OR 1.04, 95% CI 0.89-1.22, p = 0.97, I2 0%). CONCLUSION: Meta-analysis of observational and randomised studies showed that right hemicolectomy with complete mesocolic excision for primary right colon cancer improves oncologic results without increasing morbidity/mortality. These results need to be confirmed by high-quality evidence and randomised trials in selected patients to assess who may benefit from the procedure.


Asunto(s)
Neoplasias del Colon , Laparoscopía , Mesocolon , Adulto , Humanos , Neoplasias del Colon/patología , Escisión del Ganglio Linfático/métodos , Ganglios Linfáticos/patología , Supervivencia sin Enfermedad , Colectomía/métodos , Mesocolon/cirugía , Mesocolon/patología , Laparoscopía/métodos , Resultado del Tratamiento
3.
Rev Sci Instrum ; 93(12): 124901, 2022 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-36586892

RESUMEN

We demonstrate multiplexed readout of 43 transition edge sensor (TES) bolometers operating at 90 mK using a frequency division multiplexing (FDM) readout chain with bias frequencies ranging from 1 to 3.5 MHz and a typical frequency spacing of 32 kHz. We improve the previously reported performance of our FDM system by two important steps. First, we replace the coplanar wires with microstrip wires, which minimize the cross talk from mutual inductance. From the measured electrical cross talk (ECT) map, the ECT of all pixels is carrier leakage dominated. Only five pixels show an ECT level higher than 1%. Second, we reduce the thermal response speed of the TES detectors by a factor of 20 by increasing the heat capacity of the TES, which allows us to bias all TES detectors below 50% in transition without oscillations. We compare the current-voltage curves and noise spectra of the TESs measured in single-pixel mode and multiplexing mode. We also compare the noise equivalent power (NEP) and the saturation power of the bolometers in both modes, where 38 pixels show less than 10% difference in NEP and 5% difference in saturation power when measured in the two different modes. The measured noise spectrum is in good agreement with the simulated noise based on measured parameters from an impedance measurement, confirming that our TES is dominated by phonon noise.

4.
Rev Sci Instrum ; 92(1): 014710, 2021 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-33514257

RESUMEN

We have characterized and mapped the electrical cross talk (ECT) of a frequency division multiplexing (FDM) system with a transition edge sensor (TES) bolometer array, which is intended for space applications. By adding a small modulation at 120 Hz to the AC bias voltage of one bolometer and measuring the cross talk response in the current noise spectra of the others simultaneously, we have for the first time mapped the ECT level of 61 pixels with a nominal frequency spacing of 32 kHz in a 61 × 61 matrix and a carrier frequency ranging from 1 MHz to 4 MHz. We find that about 94% of the pixels show an ECT level of less than 0.4%. Only the adjacent pixels reach this level, and the ECT for the rest of the pixels is less than 0.1%. We also observe higher ECT levels, up to 10%, between some of the pixels, which have bundled long, parallel coplanar wires connecting TES bolometers to inductor-capacitor filters. In this case, the high mutual inductances dominate. To mitigate this source of ECT, the coplanar wires should be replaced by microstrip wires in the array. Our study suggests that an FDM system can have a relatively low ECT level, e.g., around 0.4% if the frequency spacing is 30 kHz. Our results successfully demonstrate a low electrical cross talk for a space FDM technology.

5.
Phys Rev Lett ; 121(15): 157701, 2018 Oct 12.
Artículo en Inglés | MEDLINE | ID: mdl-30362798

RESUMEN

Nonequilibrium quasiparticle excitations degrade the performance of a variety of superconducting circuits. Understanding the energy distribution of these quasiparticles will yield insight into their generation mechanisms, the limitations they impose on superconducting devices, and how to efficiently mitigate quasiparticle-induced qubit decoherence. To probe this energy distribution, we systematically correlate qubit relaxation and excitation with charge-parity switches in an offset-charge-sensitive transmon qubit, and find that quasiparticle-induced excitation events are the dominant mechanism behind the residual excited-state population in our samples. By itself, the observed quasiparticle distribution would limit T_{1} to ≈200 µs, which indicates that quasiparticle loss in our devices is on equal footing with all other loss mechanisms. Furthermore, the measured rate of quasiparticle-induced excitation events is greater than that of relaxation events, which signifies that the quasiparticles are more energetic than would be predicted from a thermal distribution describing their apparent density.

6.
Phys Rev Lett ; 121(4): 047001, 2018 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-30095962

RESUMEN

The modern understanding of the Josephson effect in mesosopic devices derives from the physics of Andreev bound states, fermionic modes that are localized in a superconducting weak link. Recently, Josephson junctions constructed using semiconducting nanowires have led to the realization of superconducting qubits with gate-tunable Josephson energies. We have used a microwave circuit QED architecture to detect Andreev bound states in such a gate-tunable junction based on an aluminum-proximitized indium arsenide nanowire. We demonstrate coherent manipulation of these bound states, and track the bound-state fermion parity in real time. Individual parity-switching events due to nonequilibrium quasiparticles are observed with a characteristic timescale T_{parity}=160±10 µs. The T_{parity} of a topological nanowire junction sets a lower bound on the bandwidth required for control of Majorana bound states.

7.
Neth J Med ; 75(10): 443-447, 2017 12.
Artículo en Inglés | MEDLINE | ID: mdl-29256411

RESUMEN

BACKGROUND: Community dwelling elderly who are temporarily unable to live independently due to functional decline can be referred for geriatric rehabilitation care at a nursing home. This referral is always preceded by a comprehensive geriatric assessment (CGA) by a geriatrician in hospital to rule out an indication for clinical admission and to evaluate geriatric multimorbidity. Because there is little evidence of the effectiveness of this procedure, we aimed to evaluate the results of this assessment and to elaborate on its relevance. METHODS: All patients who were referred by their general practitioner for a CGA in our hospital prior to geriatric rehabilitation care between March and December 2016 were included prospectively. Data were analysed retrospectively. Our primary aim was to describe the percentage of patients with an indication for hospital admission. Other outcomes included new diagnostic findings from the geriatric assessment and recommendations given to the elderly care physician in the geriatric rehabilitation facility. RESULTS: Of the 32 assessed patients, 25% required admission to hospital, either due to somatic illness, mainly infections or suspected neurological disorders, needing clinical treatment, or for further diagnostics. New findings by geriatric assessment mostly concerned vitamin deficiency and infection, for which treatment recommendations were given to the elderly care physician. CONCLUSION: Geriatric assessment prior to geriatric rehabilitation referral is essential as it identifies patients needing hospital care, which cannot be provided at a nursing home. Furthermore, the assessment results in important recommendations to the elderly care physician in the geriatric rehabilitation facility.


Asunto(s)
Evaluación Geriátrica , Derivación y Consulta , Rehabilitación , Anciano , Anciano de 80 o más Años , Femenino , Geriatría , Hospitalización , Humanos , Vida Independiente , Masculino , Países Bajos , Casas de Salud , Estudios Retrospectivos
8.
Phys Rev Lett ; 115(12): 127002, 2015 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-26431010

RESUMEN

We report the realization of quantum microwave circuits using hybrid superconductor-semiconductor Josephson elements comprised of InAs nanowires contacted by NbTiN. Capacitively shunted single elements behave as transmon circuits with electrically tunable transition frequencies. Two-element circuits also exhibit transmonlike behavior near zero applied flux but behave as flux qubits at half the flux quantum, where nonsinusoidal current-phase relations in the elements produce a double-well Josephson potential. These hybrid Josephson elements are promising for applications requiring microwave superconducting circuits operating in a magnetic field.

9.
Sci Total Environ ; 512-513: 562-571, 2015 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-25647371

RESUMEN

Marine bacteria isolated from natural seawater were used to test their capacity to promote barite precipitation under laboratory conditions. Seawater samples were collected in the western and eastern Mediterranean at 250 m and 200 m depths, respectively, since marine barite formation is thought to occur in the upper water column. The results indicate that Pseudoalteromonas sp., Idiomarina sp. and Alteromonas sp. actually precipitate barite under experimental conditions. Barite precipitates show typical characteristics of microbial precipitation in terms of size, morphology and composition. Initially, a P-rich phase precipitates and subsequently evolves to barite crystals with low P contents. Under laboratory conditions barite formation correlates with extracellular polymeric substances (EPS) production. Barite precipitates are particularly abundant in cultures where EPS production is similarly abundant. Our results further support the idea that bacteria may provide appropriate microenvironments for mineral precipitation in the water column. Therefore, bacterial production in the past ocean should be considered when using Ba proxies for paleoproductivity reconstructions.


Asunto(s)
Bacterias/metabolismo , Sulfato de Bario/metabolismo , Agua de Mar/microbiología , Contaminantes Químicos del Agua/metabolismo , Sulfato de Bario/análisis , Clima , Mar Mediterráneo , Filogenia , ARN Ribosómico 16S , Agua de Mar/química , Contaminantes Químicos del Agua/análisis
10.
Phys Rev Lett ; 112(7): 070502, 2014 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-24579578

RESUMEN

We present an indirect two-qubit parity meter in planar circuit quantum electrodynamics, realized by discrete interaction with an ancilla and a subsequent projective ancilla measurement with a dedicated, dispersively coupled resonator. Quantum process tomography and successful entanglement by measurement demonstrate that the meter is intrinsically quantum nondemolition. Separate interaction and measurement steps allow the execution of subsequent data-qubit operations in parallel with ancilla measurement, offering time savings over continuous schemes.

11.
Nature ; 502(7471): 350-4, 2013 Oct 17.
Artículo en Inglés | MEDLINE | ID: mdl-24132292

RESUMEN

The stochastic evolution of quantum systems during measurement is arguably the most enigmatic feature of quantum mechanics. Measuring a quantum system typically steers it towards a classical state, destroying the coherence of an initial quantum superposition and the entanglement with other quantum systems. Remarkably, the measurement of a shared property between non-interacting quantum systems can generate entanglement, starting from an uncorrelated state. Of special interest in quantum computing is the parity measurement, which projects the state of multiple qubits (quantum bits) to a state with an even or odd number of excited qubits. A parity meter must discern the two qubit-excitation parities with high fidelity while preserving coherence between same-parity states. Despite numerous proposals for atomic, semiconducting and superconducting qubits, realizing a parity meter that creates entanglement for both even and odd measurement results has remained an outstanding challenge. Here we perform a time-resolved, continuous parity measurement of two superconducting qubits using the cavity in a three-dimensional circuit quantum electrodynamics architecture and phase-sensitive parametric amplification. Using postselection, we produce entanglement by parity measurement reaching 88 per cent fidelity to the closest Bell state. Incorporating the parity meter in a feedback-control loop, we transform the entanglement generation from probabilistic to fully deterministic, achieving 66 per cent fidelity to a target Bell state on demand. These realizations of a parity meter and a feedback-enabled deterministic measurement protocol provide key ingredients for active quantum error correction in the solid state.

12.
Phys Rev Lett ; 110(6): 067004, 2013 Feb 08.
Artículo en Inglés | MEDLINE | ID: mdl-23432295

RESUMEN

We study spin relaxation and diffusion in an electron-spin ensemble of nitrogen impurities in diamond at low temperature (0.25-1.2 K) and polarizing magnetic field (80-300 mT). Measurements exploit field-controlled coupling of the ensemble to two modes of a transmission-line resonator. The observed temperature-independent spin relaxation time indicates that spin outdiffusion across the mode volume dominates over spin-lattice relaxation. Depolarization of one hyperfine-split subensemble by pumping of another indicates fast cross relaxation, with implications for the use of subensembles as independent quantum memories.

13.
Geobiology ; 9(5): 377-93, 2011 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-21884361

RESUMEN

Recent studies have shown that ancient plankton DNA can be recovered from Holocene lacustrine and marine sediments, including from species that do not leave diagnostic microscopic fossils in the sediment record. Therefore, the analysis of this so-called fossil plankton DNA is a promising approach for refining paleoecological and paleoenvironmental information. However, further studies are needed to reveal whether DNA of past plankton is preserved beyond the Holocene. Here, we identified past eukaryotic plankton members based on 18S rRNA gene profiling in eastern Mediterranean Holocene and Pleistocene sapropels S1 (~9 ka), S3 (~80 ka), S4 (~105 ka), and S5 (~125 ka). The majority of preserved ~400- to 500-bp-long 18S rDNA fragments of microalgae that were studied in detail (i.e. from haptophyte algae and dinoflagellates) were found in the youngest sapropel S1, whereas their specific lipid biomarkers (long-chain alkenones and dinosterol) were also abundant in sediments deposited between 80 and 124 ka BP. The late-Pleistocene sediments mainly contained eukaryotic DNA of marine fungi and from terrestrial plants, which could have been introduced via the river Nile at the time of deposition and preserved in pollen grains. A parallel analysis of Branched and Isoprenoid Tetraethers (i.e. BIT index) showed that most of the organic matter in the eastern Mediterranean sediment record was of marine (e.g. pelagic) origin. Therefore, the predominance of terrestrial plant DNA over plankton DNA in older sapropels suggests a preferential degradation of marine plankton DNA.


Asunto(s)
Dinoflagelados/genética , Sedimentos Geológicos/química , Haptophyta/genética , Paleontología/métodos , Reacción en Cadena de la Polimerasa/métodos , Benzopiranos/análisis , Biomarcadores/análisis , Biomasa , Colestenos/análisis , Electroforesis en Gel de Gradiente Desnaturalizante/métodos , Dinoflagelados/química , Dinoflagelados/clasificación , Éteres/análisis , Eucariontes/química , Eucariontes/clasificación , Eucariontes/genética , Fósiles , Haptophyta/química , Haptophyta/clasificación , Sustancias Húmicas/análisis , Cetonas/análisis , Mar Mediterráneo , Filogenia , Fitoplancton/química , Fitoplancton/clasificación , Fitoplancton/genética , ARN Ribosómico 16S/genética , ARN Ribosómico 16S/aislamiento & purificación
14.
Phys Rev Lett ; 106(8): 080802, 2011 Feb 25.
Artículo en Inglés | MEDLINE | ID: mdl-21405560

RESUMEN

We experimentally demonstrate single-spin magnetometry with multipulse sensing sequences. The use of multipulse sequences can greatly increase the sensing time per measurement shot, resulting in enhanced ac magnetic field sensitivity. We theoretically derive and experimentally verify the optimal number of sensing cycles, for which the effects of decoherence and increased sensing time are balanced. We perform these experiments for oscillating magnetic fields with fixed phase as well as for fields with random phase. Finally, by varying the phase and frequency of the ac magnetic field, we measure the full frequency-filtering characteristics of different multipulse schemes and discuss their use in magnetometry applications.


Asunto(s)
Magnetismo , Diamante/química , Nitrógeno/química
15.
Phys Rev Lett ; 105(7): 077601, 2010 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-20868076

RESUMEN

Long-time dynamical decoupling and quantum control of qubits require high-precision control pulses. Full characterization (quantum tomography) of imperfect pulses presents a bootstrap problem: tomography requires initial states of a qubit which cannot be prepared without perfect pulses. We present a protocol for pulse error analysis, specifically tailored for a wide range of the single solid-state electron spins. Using a single electron spin of a nitrogen-vacancy center in diamond, we experimentally verify the correctness of the protocol, and demonstrate its usefulness for quantum control tasks.

16.
Science ; 330(6000): 60-3, 2010 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-20829452

RESUMEN

Controlling the interaction of a single quantum system with its environment is a fundamental challenge in quantum science and technology. We strongly suppressed the coupling of a single spin in diamond with the surrounding spin bath by using double-axis dynamical decoupling. The coherence was preserved for arbitrary quantum states, as verified by quantum process tomography. The resulting coherence time enhancement followed a general scaling with the number of decoupling pulses. No limit was observed for the decoupling action up to 136 pulses, for which the coherence time was enhanced more than 25 times compared to that obtained with spin echo. These results uncover a new regime for experimental quantum science and allow us to overcome a major hurdle for implementing quantum information protocols.

17.
Geobiology ; 6(5): 450-60, 2008 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-19076636

RESUMEN

The diversity of the methyl-coenzyme reductase A (mcrA) and 16S rRNA genes was investigated in gas hydrate containing sediment from the Kazan mud volcano, eastern Mediterranean Sea. mcrA was detected only at 15 and 20 cm below seafloor (cmbsf) from a 40-cm long push core, while based on chemical profiles of methane, sulfate, and sulfide, possible anaerobic oxidation of methane (AOM) depth was inferred at 12-15 cmbsf. The phylogenetic relationships of the obtained mcrA, archaeal and bacterial 16S rRNA genes, showed that all the found sequences were found in both depths and at similar relative abundances. mcrA diversity was low. All sequences were related to the Methanosarcinales, with the most dominant (77.2%) sequences falling in group mcrA-e. The 16S rRNA-based archaeal diversity also revealed low diversity and clear dominance (72.8% of all archaeal phylotypes) of the Methanosarcinales and, in particular, ANME-2c. Bacteria showed higher diversity but 83.2% of the retrieved phylotypes from both sediment layers belonged to the delta-Proteobacteria. These phylotypes fell in the SEEP-SRB1 putative AOM group. In addition, the rest of the less abundant phylotypes were related to yet-uncultivated representatives of the Actinobacteria, Spirochaetales, and candidate divisions OP11 and WS3 from gas hydrate-bearing habitats. These phylotype patterns indicate that AOM is occurring in the 15 and 20 cmbsf sediment layers.


Asunto(s)
Archaea/clasificación , Bacterias/clasificación , Biodiversidad , Sedimentos Geológicos/microbiología , Metano/metabolismo , Oxidorreductasas/genética , ARN Ribosómico 16S/genética , Archaea/genética , Archaea/metabolismo , Bacterias/genética , Bacterias/metabolismo , Mar Mediterráneo , Datos de Secuencia Molecular , Filogenia , Análisis de Secuencia de ADN , Homología de Secuencia
18.
J Sports Med Phys Fitness ; 46(2): 202-8, 2006 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-16823348

RESUMEN

AIM: The aim of this study was to assess the applicability of a regression model for peak power (PP) and total mechanical work (TMW) for healthy children, adolescents and young adults especially in the extreme ranges of stature, mass, and body mass index (BMI). METHODS: A total of 454 children, adolescents and young adults aged 6-20 years volunteered for the study. Subjects, whose stature, mass and BMI were between the 10(th) and the 90(th) centile, were selected to calculate the prediction equation: 267 subjects fulfilled these criteria. Each subject performed two unilateral Wingate tests (ULWAnT), one with each leg. PP (Watts) and TMW (Joules) of the left and right leg were averaged for each individual. Ln(mass), in(stature), age, age(2), gender, and age x gender were used as predictors for in(PP) and ln(TMW). The applicability of the prediction equation was tested on individuals who were less than the 10(th) centile or greater than the 90(th) centile for stature, body mass and BMI. RESULTS: All independent variables were statistically significant (P<0.05) predictors of in(PP), adjusted R(2)=0.93 and all but gender were significant predictors for in(TMW), adjusted R(2)=0.95. However, measured in(PP) and in(TMW) were significantly lower than predicted in(PP) and in(TMW) for subjects >90th centile for stature, body mass, or BMI. CONCLUSIONS: the prediction equations overestimated PP and TMW in children, adolescents and young adults who were heavier than the reference subjects, as indicated by a relatively high body mass or high BMI for age or were taller than the reference subjects. The findings might reflect a deficit in anaerobic capacity in children, adolescents and young adults with relatively large body size for their age.


Asunto(s)
Tamaño Corporal/fisiología , Fuerza Muscular/fisiología , Esfuerzo Físico/fisiología , Adolescente , Adulto , Factores de Edad , Estatura/fisiología , Índice de Masa Corporal , Peso Corporal/fisiología , Niño , Prueba de Esfuerzo , Femenino , Humanos , Extremidad Inferior/fisiología , Masculino , Modelos Biológicos , Factores Sexuales
19.
Neuroimage ; 26(2): 513-24, 2005 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-15907308

RESUMEN

Individuals with Chronic Fatigue Syndrome (CFS) often have difficulties with complex auditory information processing. In a series of two Blood Oxygen Level Dependent (BOLD) functional Magnetic Resonance Imaging (fMRI) studies, we compared BOLD signal changes between Controls and individuals with CFS who had documented difficulties in complex auditory information processing (Study 1) and those who did not (Study 2) in response to performance on a simple auditory monitoring and a complex auditory information processing task (mPASAT). We hypothesized that under conditions of cognitive challenge: (1) individuals with CFS who have auditory information processing difficulties will utilize frontal and parietal brain regions to a greater extent than Controls and (2) these differences will be maintained even when objective difficulties in this domain are controlled for. Using blocked design fMRI paradigms in both studies, we first presented the auditory monitoring task followed by the mPASAT. Within and between regions of interest (ROI), group analyses were performed for both studies with statistical parametric mapping (SPM99). Findings showed that individuals with CFS are able to process challenging auditory information as accurately as Controls but utilize more extensive regions of the network associated with the verbal WM system. Individuals with CFS appear to have to exert greater effort to process auditory information as effectively as demographically similar healthy adults. Our findings provide objective evidence for the subjective experience of cognitive difficulties in individuals with CFS.


Asunto(s)
Cognición/fisiología , Síndrome de Fatiga Crónica/patología , Síndrome de Fatiga Crónica/psicología , Memoria a Corto Plazo/fisiología , Oxígeno/sangre , Estimulación Acústica , Adulto , Percepción Auditiva/fisiología , Interpretación Estadística de Datos , Femenino , Humanos , Interpretación de Imagen Asistida por Computador , Imagen por Resonancia Magnética , Masculino , Red Nerviosa/fisiología , Pruebas Neuropsicológicas , Desempeño Psicomotor/fisiología
20.
Biomed Microdevices ; 6(3): 191-202, 2004 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-15377828

RESUMEN

Here we describe a post-translational modification of SC-63032, a variant of the species restricted, multi-lineage hematopoeitic factor human interleukin-3 (hIL-3). We have made two new dendritic polymer (polyamidoamine or PAMAM dendrimers, generation 5)-SC-63032 bioconjugates. Using two distinct chemistries (one of which is novel to this work), we achieved site-specific conjugation with respect to the amino acid in the proteins ligated to the dendrimers. In both bioconjugates, conjugated cytokine maintains its ability to bind the hIL-3 alpha receptor subunit, but is significantly (about 10-fold) less potent in inducing hIL-3 dependent in vitro cell proliferation than is the free cytokine. In vivo data indicates that conjugation decreases the immunogenicity of the conjugated cytokine modestly. In the absence of pharmacokinetic or biodistribution effects associated with the bioconjugates that increase their potency in vivo (which can only be tested in a higher primate, due to the species restriction of hIL-3 and its derivatives), these immune mitigation effects may be too small to be therapeutically significant. Though unmodified PAMAM dendrimers fail to elicit an antibody response in mice, protein conjugation to dendrimers haptenizes them, and a dendrimer-specific antibody response is produced. In toto, the principal limitation of the dendrimer-cytokine bioconjugates herein is in their reduced receptor affinity and potency in vitro. Were the in vivo potency of the bioconjugates to parallel the in vitro potency of the conjugates reported here, it is likely that particular dendrimer bioconjugates could not justify their higher costs of goods relative to the parent SC-63032 molecule, though retention of SC-63032 biological activities in conjugates suggests that other cytokine-dendrimer bioconjugates may be bioactive. This is good news to the nanotechnology community, in as much as PAMAM dendrimers are among the monodisperse polymeric nanomaterials available, and these results show that they can be used successfully in conjugates to bioactive proteins.


Asunto(s)
Riñón/metabolismo , Poliaminas/química , Ingeniería de Proteínas/métodos , Proteínas/inmunología , Proteínas/metabolismo , Receptores de Interleucina-3/metabolismo , Animales , Materiales Biocompatibles/química , Línea Celular , Cricetinae , Citocinas/química , Citocinas/inmunología , Citocinas/metabolismo , Femenino , Ratones , Ratones Endogámicos BALB C , Polímeros/química , Unión Proteica , Proteínas/química , Proteínas Recombinantes de Fusión/química , Proteínas Recombinantes de Fusión/inmunología , Proteínas Recombinantes de Fusión/metabolismo
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