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1.
Opt Express ; 27(22): 31713-31726, 2019 Oct 28.
Artículo en Inglés | MEDLINE | ID: mdl-31684398

RESUMEN

Propagation losses in transmission media limit the transmission distance of optical signals. In the case where the signal is made up of quantum optical states, conventional deterministic optical amplification schemes cannot be used to increase the transmission distance as the copying of an arbitrary and unknown quantum state is forbidden. One strategy that can offset propagation loss is the use of probabilistic, or non-deterministic, amplification schemes - an example of which is the state comparison amplifier. Here we report a state comparison amplifier implemented in a compact, fiber-coupled femtosecond laser-written waveguide chip as opposed to the large, bulk-optical components of previous designs. This pathfinder on-chip implementation of the quantum amplifier has resulted in several performance improvements: the polarization integrity of the written waveguides has resulted in improved visibility of the amplifier interferometers; the potential of substantially-reduced losses throughout the amplifier configuration; and a more compact and environmentally-stable amplifier which is scalable to more complex networks.

2.
Blood Adv ; 3(22): 3503-3514, 2019 Nov 26.
Artículo en Inglés | MEDLINE | ID: mdl-31725895

RESUMEN

Aberrant JAK2 tyrosine kinase signaling drives the development of Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs), including polycythemia vera, essential thrombocythemia, and primary myelofibrosis. However, JAK2 kinase inhibitors have failed to significantly reduce allele burden in MPN patients, underscoring the need for improved therapeutic strategies. Members of the PIM family of serine/threonine kinases promote cellular proliferation by regulating a variety of cellular processes, including protein synthesis and the balance of signaling that regulates apoptosis. Overexpression of PIM family members is oncogenic, exemplified by their ability to induce lymphomas in collaboration with c-Myc. Thus, PIM kinases are potential therapeutic targets for several malignancies such as solid tumors and blood cancers. We and others have shown that PIM inhibitors augment the efficacy of JAK2 inhibitors by using in vitro models of MPNs. Here we report that the recently developed pan-PIM inhibitor INCB053914 augments the efficacy of the US Food and Drug Administration-approved JAK1/2 inhibitor ruxolitinib in both in vitro and in vivo MPN models. INCB053914 synergizes with ruxolitinib to inhibit cell growth in JAK2-driven MPN models and induce apoptosis. Significantly, low nanomolar INCB053914 enhances the efficacy of ruxolitinib to inhibit the neoplastic growth of primary MPN patient cells, and INCB053914 antagonizes ruxolitinib persistent myeloproliferation in vivo. These findings support the notion that INCB053914, which is currently in clinical trials in patients with advanced hematologic malignancies, in combination with ruxolitinib may be effective in MPN patients, and they support the clinical testing of this combination in MPN patients.

3.
Geriatr Nurs ; 40(4): 353-359, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30878281

RESUMEN

This descriptive study sought to establish an oral health baseline of need for enrollees at a Program of All-Inclusive Care for the Elderly (PACE) and identify opportunities for nursing interventions. The Oral Health Assessment Tool (OHAT) was applied to a random sample of 120 enrollees, 64 of whom met inclusion criteria, agreed to participate to assess their oral health status, and were included in the analysis. The mean OHAT score was 4.4 (SD = 2.6; range 0-12). Higher scores indicate poorer oral health. The oral conditions found needing the most attention were gums, saliva, natural teeth, dentures, and oral cleanliness. Oral cleanliness scored the worst on the OHAT, highlighting opportunities for nursing interventions and the necessity for oral hygiene routines. This study also identifies the need for nurses to address enrollees' oral health and relay information back to the PACE interdisciplinary team (IDT) to initiate referrals to the dentist as needed.

4.
Sci Rep ; 7(1): 3235, 2017 06 12.
Artículo en Inglés | MEDLINE | ID: mdl-28607475

RESUMEN

Ensuring the integrity and transferability of digital messages is an important challenge in modern communications. Although purely mathematical approaches exist, they usually rely on the computational complexity of certain functions, in which case there is no guarantee of long-term security. Alternatively, quantum digital signatures offer security guaranteed by the physical laws of quantum mechanics. Prior experimental demonstrations of quantum digital signatures in optical fiber have typically been limited to operation over short distances and/or operated in a laboratory environment. Here we report the experimental transmission of quantum digital signatures over channel losses of up to 42.8 ± 1.2 dB in a link comprised of 90 km of installed fiber with additional optical attenuation introduced to simulate longer distances. The channel loss of 42.8 ± 1.2 dB corresponds to an equivalent distance of 134.2 ± 3.8 km and this represents the longest effective distance and highest channel loss that quantum digital signatures have been shown to operate over to date. Our theoretical model indicates that this represents close to the maximum possible channel attenuation for this quantum digital signature protocol, defined as the loss for which the signal rate is comparable to the dark count rate of the detectors.

5.
Opt Lett ; 41(21): 4883-4886, 2016 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-27805641

RESUMEN

Quantum digital signatures (QDSs) apply quantum mechanics to the problem of guaranteeing message integrity and non-repudiation with information-theoretical security, which are complementary to the confidentiality realized by quantum key distribution (QKD). Previous experimental demonstrations have been limited to transmission distances of less than 5 km of optical fiber in a laboratory setting. Here we report, to the best of our knowledge, the first demonstration of QDSs over installed optical fiber, as well as the longest transmission link reported to date. This demonstration used a 90 km long differential phase shift QKD to achieve approximately one signed bit per second, an increase in the signature generation rate of several orders of magnitude over previous optical fiber demonstrations.

6.
Sci Rep ; 6: 36914, 2016 11 14.
Artículo en Inglés | MEDLINE | ID: mdl-27841300

RESUMEN

The NOON state, and its experimental approximation the Holland-Burnett state, have important applications in phase sensing measurement with enhanced sensitivity. However, most of the previous Holland-Burnett state interference (HBSI) experiments only investigated the area of the interference pattern in the region immediately around zero optical path length difference, while the full HBSI pattern over a wide range of optical path length differences has not yet been well explored. In this work, we experimentally and theoretically demonstrate up to six-photon HBSI and study the properties of the interference patterns over a wide range of optical path length differences. It was found that the shape, the coherence time and the visibility of the interference patterns were strongly dependent on the detection schemes. This work paves the way for applications which are based on the envelope of the HBSI pattern, such as quantum spectroscopy and quantum metrology.

7.
Phys Rev Lett ; 114(12): 120505, 2015 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-25860729

RESUMEN

We present an experimental demonstration of a practical nondeterministic quantum optical amplification scheme that employs two mature technologies, state comparison and photon subtraction, to achieve amplification of known sets of coherent states with high fidelity. The amplifier uses coherent states as a resource rather than single photons, which allows for a relatively simple light source, such as a diode laser, providing an increased rate of amplification. The amplifier is not restricted to low amplitude states. With respect to the two key parameters, fidelity and the amplified state production rate, we demonstrate significant improvements over previous experimental implementations, without the requirement of complex photonic components. Such a system may form the basis of trusted quantum repeaters in nonentanglement-based quantum communications systems with known phase alphabets, such as quantum key distribution or quantum digital signatures.

8.
Phys Rev Lett ; 113(4): 040502, 2014 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-25105603

RESUMEN

Digital signatures are widely used to provide security for electronic communications, for example, in financial transactions and electronic mail. Currently used classical digital signature schemes, however, only offer security relying on unproven computational assumptions. In contrast, quantum digital signatures offer information-theoretic security based on laws of quantum mechanics. Here, security against forging relies on the impossibility of perfectly distinguishing between nonorthogonal quantum states. A serious drawback of previous quantum digital signature schemes is that they require long-term quantum memory, making them impractical at present. We present the first realization of a scheme that does not need quantum memory and which also uses only standard linear optical components and photodetectors. In our realization, the recipients measure the distributed quantum signature states using a new type of quantum measurement, quantum state elimination. This significantly advances quantum digital signatures as a quantum technology with potential for real applications.

9.
Nat Commun ; 3: 1174, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-23132024

RESUMEN

Digital signatures are frequently used in data transfer to prevent impersonation, repudiation and message tampering. Currently used classical digital signature schemes rely on public key encryption techniques, where the complexity of so-called 'one-way' mathematical functions is used to provide security over sufficiently long timescales. No mathematical proofs are known for the long-term security of such techniques. Quantum digital signatures offer a means of sending a message, which cannot be forged or repudiated, with security verified by information-theoretical limits and quantum mechanics. Here we demonstrate an experimental system, which distributes quantum signatures from one sender to two receivers and enables message sending ensured against forging and repudiation. Additionally, we analyse the security of the system in some typical scenarios. Our system is based on the interference of phase-encoded coherent states of light and our implementation utilizes polarization-maintaining optical fibre and photons with a wavelength of 850 nm.

11.
Appl Opt ; 48(32): 6241-51, 2009 Nov 10.
Artículo en Inglés | MEDLINE | ID: mdl-19904323

RESUMEN

We describe a scanning time-of-flight system which uses the time-correlated single-photon counting technique to produce three-dimensional depth images of distant, noncooperative surfaces when these targets are illuminated by a kHz to MHz repetition rate pulsed laser source. The data for the scene are acquired using a scanning optical system and an individual single-photon detector. Depth images have been successfully acquired with centimeter xyz resolution, in daylight conditions, for low-signature targets in field trials at distances of up to 325 m using an output illumination with an average optical power of less than 50 microW.

12.
Organogenesis ; 5(4): 201-10, 2009 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-20539739

RESUMEN

The Xenopus laevis cyclin dependent kinase inhibitor p27(Xic1) has been shown to be involved in exit from the cell cycle and differentiation of cells into a quiescent state in the nervous system, muscle tissue, heart and retina. We show that p27(Xic1) is expressed in the developing kidney in the nephrostomal regions. Using overexpression and morpholino oligonucleotide (MO) knock-down approaches we show normal levels of p27(Xic1) regulate pronephros organ size by regulating cell cycle exit. Knock-down of p27(Xic1) expression using a MO prevented myogenesis, as previously reported; an effect that subsequently inhibits pronephrogenesis. Furthermore, we show that normal levels of p27(Xic1) are required for somite segmentation also through its cell cycle control function. Finally, we provide evidence to suggest correct paraxial mesoderm segmentation is not necessary for pronephric induction in the intermediate mesoderm. These results indicate novel developmental roles for p27(Xic1), and reveal its differentiation function is not universally utilised in all developing tissues.

13.
Acta Crystallogr D Biol Crystallogr ; 64(Pt 11): 1123-30, 2008 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-19020350

RESUMEN

Structural crystallography aims to provide a three-dimensional representation of macromolecules. Many parts of the multistep process to produce the three-dimensional structural model have been automated, especially through various structural genomics projects. A key step is the production of crystals for diffraction. The target macromolecule is combined with a large and chemically diverse set of cocktails with some leading ideally, but infrequently, to crystallization. A variety of outcomes will be observed during these screening experiments that typically require human interpretation for classification. Human interpretation is neither scalable nor objective, highlighting the need to develop an automatic computer-based image classification. As a first step towards automated image classification, 147,456 images representing crystallization experiments from 96 different macromolecular samples were manually classified. Each image was classified by three experts into seven predefined categories or their combinations. The resulting data where all three observers are in agreement provides one component of a truth set for the development and rigorous testing of automated image-classification systems and provides information about the chemical cocktails used for crystallization. In this paper, the details of this study are presented.


Asunto(s)
Cristalografía por Rayos X/métodos , Procesamiento de Imagen Asistida por Computador/métodos , Sustancias Macromoleculares/química , Enseñanza/métodos , Algoritmos , Gráficos por Computador , Cristalización , Cristalografía por Rayos X/clasificación , Procesamiento Automatizado de Datos , Humanos , Procesamiento de Imagen Asistida por Computador/clasificación , Modelos Moleculares , Enseñanza/tendencias
14.
Acta Crystallogr D Biol Crystallogr ; 64(Pt 11): 1131-7, 2008 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-19020351

RESUMEN

In the automated image analysis of crystallization experiments, representative examples of outcomes can be obtained rapidly. However, while the outcomes appear to be diverse, the number of crystalline outcomes can be small. To complement a training set from the visual observation of 147 456 crystallization outcomes, a set of crystal images was produced from 106 and 163 macromolecules under study for the North East Structural Genomics Consortium (NESG) and Structural Genomics of Pathogenic Protozoa (SGPP) groups, respectively. These crystal images have been combined with the initial training set. A description of the crystal-enriched data set and a preliminary analysis of outcomes from the data are described.


Asunto(s)
Cristalografía por Rayos X/métodos , Procesamiento de Imagen Asistida por Computador/métodos , Sustancias Macromoleculares/química , Enseñanza/métodos , Gráficos por Computador , Cristalización , Cristalografía por Rayos X/clasificación , Sistemas de Administración de Bases de Datos , Humanos , Procesamiento de Imagen Asistida por Computador/clasificación , Modelos Moleculares , Polietilenglicoles/química , Polietilenglicoles/metabolismo , Enseñanza/tendencias
15.
Organogenesis ; 3(2): 83-92, 2007 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-19279706

RESUMEN

Anxa4 belongs to the multigenic annexin family of proteins which are characterized by their ability to interact with membranes in a calcium-dependent manner. Defined as a marker for polarized epithelial cells, Anxa4 is believed to be involved in many cellular processes but its functions in vivo are still poorly understood. Previously, we cloned Xanx4 in Xenopus laevis (now referred to as anxa4a) and demonstrated its role during organogenesis of the pronephros, providing the first evidence of a specific function for this protein during the development of a vertebrate. Here, we describe the strict conservation of protein sequence and functional domains of anxa4 during vertebrate evolution. We also identify the paralog of anxa4a, anxa4b and show its specific temporal and spatial expression pattern is different from anxa4a. We show that anxa4 orthologs in X. laevis and tropicalis display expression domains in different organ systems. Whilst the anxa4a gene is mainly expressed in the kidney, Xt anxa4 is expressed in the liver. Finally, we demonstrate Xt anxa4 and anxa4a can display conserved function during kidney organogenesis, despite the fact that Xt anxa4 transcripts are not expressed in this domain. This study highlights the divergence of expression of homologous genes during Xenopus evolution and raises the potential problems of using X. tropicalis promoters in X. laevis.

16.
Acta Cytol ; 50(2): 164-77, 2006 Mar-Apr.
Artículo en Inglés | MEDLINE | ID: mdl-16610684

RESUMEN

OBJECTIVE: To develop a local quality assurance program in cytopathology based on circulation of patient specimens on glass slides, with limited resources. STUDY DESIGN: A working group was set up for design and running of the program. Participation is on a laboratory basis. The scope and frequency of testing are defined. Well-documented cases (including gynecologic, nongynecologic and fine needle aspiration cytology) with commonly encountered diagnoses are collected. Consensus concerning the diagnosis, interpretive menu and scoring system is sought before the actual slide circulations using express mail. After returning their answers to the program organizer, the participating laboratories receive immediate feedback on their scores, with reference answers, explanatory notes, "whole-mount" images of glass slides and cumulative responses of peer laboratories for on-site checking. At the end of each year, an electronic file containing representative photomicrographs of all cases examined is provided to individual laboratories for their permanent records and training purposes. RESULTS: The program was launched in mid-2003. There were 24 and 27 participating laboratories from Hong Kong (and Macau) in 2003 and 2004, respectively. To date, >150 well-documented cytology cases are available in the slide pool and ready for circulation. As the revenue is mainly to cover the expenses of express mail, the program can be carried out at a relatively low cost. CONCLUSION: In order to have any cytology quality assurance program accepted by local laboratories, it has to be fair and practical. Strict confidentiality needs to be observed throughout the process. This program emphasizes both performance assessment and educational value. Adequate representation from experienced local cytology workers, detailed documentation support from authorities and assistance from dedicated staff are essential to the success of any external proficiency testing scheme. Regular review and evaluation are also necessary for continuous improvement. The Hong Kong experience can serve as an example of running a glass slide-based cytology quality assurance program in a small region with limited resources.


Asunto(s)
Técnicas de Laboratorio Clínico/normas , Laboratorios/normas , Garantía de la Calidad de Atención de Salud/organización & administración , Programas Médicos Regionales/organización & administración , Citodiagnóstico/métodos , Citodiagnóstico/normas , Evaluación del Rendimiento de Empleados , Hong Kong , Humanos , Ciencia del Laboratorio Clínico/educación , Ciencia del Laboratorio Clínico/normas , Control de Calidad , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Manejo de Especímenes/normas
17.
J Virol ; 79(21): 13630-40, 2005 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-16227283

RESUMEN

Among the more than one hundred formally described human papillomavirus (HPV) types, 18 are referred to as high-risk HPV types due to their association with anogenital cancer. Despite pathogenic similarities, these types form three remotely related taxonomic groups. One of these groups is called HPV species 9 and is formed by HPV-16, the most common and best-studied type, together with HPV-31, -33, -35, -52, -58, and -67. Previous worldwide comparisons of HPV-16 samples showed about 2% nucleotide diversity between isolates, which were subsequently termed variants. The distribution of divergent variants has been found to correlate frequently with the geographic origin and the ethnicity of the infected patients and led to the concept of unique African, European, Asian, and Native American HPV-16 variants. In the current study, we address the question of whether geography and ethnicity also correlate with sequence variations found for HPV-31, -35, -52, and -58. This was done by sequencing the long control region in samples derived from Europe, Asia, and Africa, and from immigrant populations in North and South America. We observed maximal divergence between any two variants within each of these four HPV types ranging from 1.8 to 3.6% based on nucleotide exchanges and, occasionally, on insertions and deletions. Similar to the case with HPV-16, these mutations are not random but indicate a relationship between the variants in form of phylogenetic trees. An interesting example is presented by a 16-bp insert in select variants of HPV-35, which appears to have given rise to additional variants by nucleotide exchanges within the insert. All trees showed distinct phylogenetic topologies, ranging from dichotomic branching in the case of HPV-31 to star phylogenies of the other three types. No clear similarities between these types or between these types and HPV-16 exist. While variant branches in some types were specific for Europe, Africa, or East Asia, none of the four trees reflected human evolution and spread to the extent illustrated by HPV-16. One possible explanation is that the rare HPV types that we studied spread and thereby diversified more slowly than the more abundant HPV-16 and may have established much of today's variant diversity already before the worldwide spread of humans 100,000 years ago. Most variants had prototypic amino acid sequences within the E6 oncoprotein and a segment of the L1 capsid protein. Some had one, two, or three amino acid substitutions in these regions, which might indicate biological and pathogenic diversity between the variants of each HPV type.


Asunto(s)
Genes Virales , Variación Genética , Papillomaviridae/genética , Infecciones por Papillomavirus/virología , África , Américas , Asia , Europa (Continente) , Datos de Secuencia Molecular , Filogenia
18.
Virology ; 340(1): 95-104, 2005 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-16039686

RESUMEN

Among more than 200 human papillomavirus (HPV) types presumed to exist, 18 "high-risk" HPV types are frequently found in anogenital cancer. The best studied types are HPV-16 and 18, which are only distantly related to one another and form two separate phylogenetic branches, each including six closely related types. HPV-30, 53, 56, and 66 form a third phylogenetic branch unrelated to HPV-16 and 18. Worldwide comparison of HPV-16 and 18 isolates revealed a distribution of variant genomes that correlated with the geographic origin and the ethnicity of the infected cohort and led to the concept of unique African, European, Asian, and Native American HPV-16 and 18 variants. Here, we address the question whether similar phylogenies are found for HPV-53, 56, and 66 by determining the sequence of the long control regions (LCR) of these HPVs in samples from Europe, Asia, and Africa, and from immigrant societies in North and South America. Phylogenetic trees calculated from point mutations and a few insertions/deletions affecting 2-4.2% of the nucleotide sequences were distinct for each of the three HPVs and divergent from HPV-16 and 18. In contrast to the "star-phylogenies" formed by HPV-16 and 18 variants, 44 HPV-53 isolates represented nine variants, which formed two deep dichotomic branches reminiscent of the beginning split into two new taxa, as recently observed for subtypes of HPV-44 and 68. A total of 66 HPV-56 isolates represented 17 variants, which formed three branches preferentially containing European, Asian, and African variants. Variants of a fourth branch, deeply separated from the other three, were characterized by a 25 bp insertion and created a dichotomy rather than star-like phylogeny. As it contained isolates from cohorts in all continents, it may have evolved before the spread of humans into all continents. 18 of 31 HPV-66 isolates represented the prototype clone, which was found in all parts of the world, while the remaining 13 clones formed 11 branches without any geographic association. Our findings confirm the notion of a quantitatively limited genomic diversity of each HPV type with some correlation to the geographic origin of the sample. In addition, we observed in some variants of these three HPV types mutations that affect the amino acid sequence of the E6 oncoproteins and the L1 capsid protein, supporting the possibility of immunogenic and oncogenic diversity between variants of any HPV type.


Asunto(s)
Variación Genética , Genoma Viral , Papillomaviridae/clasificación , Papillomaviridae/genética , Filogenia , Virus de la Enfermedad Aleutiana del Visón , Secuencia de Bases , Cartilla de ADN , Amplificación de Genes , Humanos , Datos de Secuencia Molecular , Papillomaviridae/patogenicidad , Reacción en Cadena de la Polimerasa
19.
J Virol ; 79(10): 6565-9, 2005 May.
Artículo en Inglés | MEDLINE | ID: mdl-15858044

RESUMEN

A human papillomavirus (HPV) type is defined as an HPV isolate whose L1 gene sequence is at least 10% different from that of any other type, while a subtype is 2 to 10% different from any HPV type. In order to analyze the phylogeny behind the subtype definition, we compared 49 isolates of HPV type 44 (HPV-44) and its subtype HPV-55, previously misclassified as a separate type, and 41 isolates of the subtype pair HPV-68a and -b, sampled from cohorts in four continents. The subtypes of each pair are separated by deep dichotomic branching, and three of the four subtypes have evolved large phylogenetic clusters of genomic variants forming a "star" phylogeny, with some branches specific for ethnically defined cohorts. We conclude that subtypes of HPV types are natural and old taxa, equivalent to types, which either diverged more recently than types or evolved more slowly.


Asunto(s)
Papillomaviridae/genética , Datos de Secuencia Molecular , Papillomaviridae/clasificación , Filogenia
20.
J Struct Biol ; 142(1): 170-9, 2003 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-12718929

RESUMEN

A method to rationally predict crystallization conditions for a previously uncrystallized macromolecule has not yet been developed. One way around this problem is to determine initial crystallization conditions by casting a wide net, surveying a large number of chemical and physical conditions to locate crystallization leads. A facility that executes the rapid survey of crystallization lead conditions is described in detail. Results and guidelines for the initial screening of crystallization conditions, applicable to both manual and robotic setups, are discussed.


Asunto(s)
Biopolímeros/química , Cristalización/métodos , Automatización , Biopolímeros/aislamiento & purificación , Computadores , Cristalización/instrumentación , Aceites , Programas Informáticos
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