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1.
Nature ; 604(7906): 451-456, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35444318

RESUMO

The ability to engineer parallel, programmable operations between desired qubits within a quantum processor is key for building scalable quantum information systems1,2. In most state-of-the-art approaches, qubits interact locally, constrained by the connectivity associated with their fixed spatial layout. Here we demonstrate a quantum processor with dynamic, non-local connectivity, in which entangled qubits are coherently transported in a highly parallel manner across two spatial dimensions, between layers of single- and two-qubit operations. Our approach makes use of neutral atom arrays trapped and transported by optical tweezers; hyperfine states are used for robust quantum information storage, and excitation into Rydberg states is used for entanglement generation3-5. We use this architecture to realize programmable generation of entangled graph states, such as cluster states and a seven-qubit Steane code state6,7. Furthermore, we shuttle entangled ancilla arrays to realize a surface code state with thirteen data and six ancillary qubits8 and a toric code state on a torus with sixteen data and eight ancillary qubits9. Finally, we use this architecture to realize a hybrid analogue-digital evolution2 and use it for measuring entanglement entropy in quantum simulations10-12, experimentally observing non-monotonic entanglement dynamics associated with quantum many-body scars13,14. Realizing a long-standing goal, these results provide a route towards scalable quantum processing and enable applications ranging from simulation to metrology.

2.
Artigo em Inglês | MEDLINE | ID: mdl-35413723

RESUMO

PURPOSE: To describe a case of a dislocated Descemet stripping automated endothelial keratoplasty (DSAEK) graft retained in-the-bag removed with pars plana vitrectomy (PPV). METHODS: Case report. RESULTS: A 69- year-old pseudophakic male who underwent a repeat DSAEK due to bullous keratopathy in the setting of multiple previous ocular surgeries presented with a vision of counting fingers. Upon examination a DSAEK graft was appreciated behind the intraocular lens obscuring the visual axis and presumed to be in the anterior vitreous. The patient underwent a 23-gauge vitrectomy and after a posterior capsulotomy, the dislocated graft was removed with a 23-gauge vitrector without complications. Best corrected visual acuity was 20/50 six months after the PPV. CONCLUSIONS: Grafts can dislocate posteriorly between the intraocular lens and the posterior capsule. The dislocated graft can be successfully extricated with a 23-gauge vitrector after a careful posterior capsulotomy, with good visual outcomes. IMPORTANCE: To our knowledge, this is the first reported case of an in-the-bag DSAEK graft posterior dislocation. Furthermore, we showed an innovative surgical technique for the removal of the dislocated graft with a 23-gauge vitrectomy and posterior capsulotomy.

3.
Cornea ; 41(2): 224-231, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-35037905

RESUMO

PURPOSE: The purpose of this study was to evaluate the risk of symptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection after corneal transplantation surgery, with cataract surgeries as controls, and the impact of the novel coronavirus disease pandemic in the clinical and surgical complications of corneal transplantation and cataract surgeries. METHODS: A retrospective matched case-control study of 480 consecutive individuals who underwent surgery at the Bascom Palmer Eye Institute between May 2020 and November 2020. A total of 240 patients who underwent corneal transplantation with tissue obtained from the Florida Lions Eye Bank were age, race, ethnicity, and sex matched with 240 patients who underwent cataract surgery during the same day and by the same surgical team. Only the first corneal transplant or cataract surgery during this period was considered for each individual. All donors and recipients were deemed SARS-CoV-2 negative by a nasopharyngeal polymerase chain reaction test before surgery. Postoperative SARS-CoV-2 infections were defined as previously SARS-CoV-2(-) individuals who developed symptoms or had a positive SARS-CoV-2 polymerase chain reaction test during the first postoperative month. RESULTS: Mean age, sex, race, and ethnicity were similar between groups. There were no differences between the corneal transplant and cataract groups in the rates of SARS-CoV-2 infection before (5.8% vs. 7.5%, P= 0.6) or after surgery (2.9% vs. 2.9%, P = 1). The rates of postoperative complications did not increase during the pandemic, compared with previously reported ranges. CONCLUSIONS: In this study, postoperative SARS-CoV-2 infection was similar for individuals undergoing corneal transplantation or cataract surgery. Further research is required to evaluate the transmission of SARS-CoV-2 through corneal tissue.


Assuntos
COVID-19/epidemiologia , Extração de Catarata , Transplante de Córnea , Complicações Pós-Operatórias/epidemiologia , SARS-CoV-2/isolamento & purificação , Idoso , Idoso de 80 Anos ou mais , COVID-19/diagnóstico , Teste de Ácido Nucleico para COVID-19 , Estudos de Casos e Controles , Bancos de Olhos/estatística & dados numéricos , Feminino , Florida/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2/genética , Doadores de Tecidos/estatística & dados numéricos , Transplantados/estatística & dados numéricos
4.
Cornea ; 2021 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-34743105

RESUMO

PURPOSE: The purpose of this study was to report the indications, ocular and systemic comorbidities, and surgical outcomes of corneal transplantation in patients older than 90 years. METHODS: A retrospective review was conducted to identify individuals 90 years and older who underwent corneal transplantation surgery at the Bascom Palmer Eye Institute between January 2013 and October 2020. Outcomes included best-corrected visual acuity and graft survival over time. Paired t tests were used to compare visual acuity preoperatively versus postoperatively. Graft survival was evaluated with Kaplan-Meier curves. RESULTS: Fifty-eight eyes of 52 consecutive individuals were included. The mean age of individuals was 92 ± 2 years; 26.9% were male; and 48.1% self-identified as non-Hispanic White and 38.5% as Hispanic. Postoperative follow-up was 14.7 ± 12.1 months. Of the 58 eyes, 44.8% (26/58) underwent penetrating keratoplasty, 46.6% (27/58) Descemet stripping automated endothelial keratoplasty, and 6.9% (4/58) keratoprosthesis. All surgeries were performed under monitored local anesthesia, without major complications. Surgical indications included pseudophakic bullous keratopathy (36.2%), glaucoma-associated corneal decompensation (27.6%), Fuchs endothelial dystrophy (25.9%), and perforated corneal ulceration (19.0%). The best-corrected visual acuity improved by 0.32 (95% confidence interval 0.14-0.50; P < 0.01) as early as 1 month postoperatively, and vision gains were sustained for at least 12 months. Graft survival probability at 12 months was 88%. CONCLUSIONS: Corneal transplantation is a safe and successful procedure in restoring the visual acuity for patients older than 90 years after careful preoperative evaluation. Further research is needed to evaluate the impact of corneal transplantation on quality of life in patients in the 10th decade of life.

5.
Nature ; 595(7866): 227-232, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34234334

RESUMO

Motivated by far-reaching applications ranging from quantum simulations of complex processes in physics and chemistry to quantum information processing1, a broad effort is currently underway to build large-scale programmable quantum systems. Such systems provide insights into strongly correlated quantum matter2-6, while at the same time enabling new methods for computation7-10 and metrology11. Here we demonstrate a programmable quantum simulator based on deterministically prepared two-dimensional arrays of neutral atoms, featuring strong interactions controlled by coherent atomic excitation into Rydberg states12. Using this approach, we realize a quantum spin model with tunable interactions for system sizes ranging from 64 to 256 qubits. We benchmark the system by characterizing high-fidelity antiferromagnetically ordered states and demonstrating quantum critical dynamics consistent with an Ising quantum phase transition in (2 + 1) dimensions13. We then create and study several new quantum phases that arise from the interplay between interactions and coherent laser excitation14, experimentally map the phase diagram and investigate the role of quantum fluctuations. Offering a new lens into the study of complex quantum matter, these observations pave the way for investigations of exotic quantum phases, non-equilibrium entanglement dynamics and hardware-efficient realization of quantum algorithms.

7.
Ocul Surf ; 21: 186-192, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34102312

RESUMO

PURPOSE: To examine whether "activated" dendritic cells (aDCs) could serve as a biomarker of systemic immune disorders in individuals with dry eye (DE) symptoms. Secondarily, to examine the impact of a topical anti-inflammatory agent on aDC number. METHODS: Retrospective analysis was conducted to identify individuals with DE symptoms who had in-vivo confocal microscopy (IVCM) imaging between October 2018 and July 2020 at the Miami Veterans Hospital. aDCs were manually quantified based on morphology. Receiver operating curve (ROC) analysis examined relationships between aDC number and systemic immune disease status. Individuals were then grouped by aDC number (≥2 versus <2) and demographics and DE parameters were examined. Paired t-test was performed to evaluated aDC number pre-vs post-initiation of an anti-inflammatory agent. RESULTS: 128 individuals were included. Their mean age was 57.1 ± 15.0 years; 71.1% were male, 53.1% self-identified as White and 24.2% as Hispanic. The mean number of aDCs in the central cornea was 1.28 ± 2.16 cells/image. The presence of ≥2 aDCs had a sensitivity of 60% and specificity of 77% for the diagnosis of a systemic immune disorder. Individuals with ≥2 aDCs were more likely to self-identify as Black, have Secondary Sjögren's, and have higher nerve fiber area and fractal dimension. In 12 individuals, aDC number decreased from 2.69 ± 2.36 to 0.58 ± 0.73 cells/image after initiation of an anti-inflammatory agent, p = 0.01. CONCLUSIONS: The presence of ≥2 aDCs in the central cornea suggests a systemic immune disorder in individuals with DE symptoms. Topical anti-inflammatory therapy can reduce the number of aDCs in the central cornea.


Assuntos
Síndromes do Olho Seco , Síndrome de Sjogren , Adulto , Idoso , Córnea , Células Dendríticas , Síndromes do Olho Seco/diagnóstico , Síndromes do Olho Seco/tratamento farmacológico , Humanos , Masculino , Microscopia Confocal , Pessoa de Meia-Idade , Fibras Nervosas , Estudos Retrospectivos
8.
Alzheimers Dement ; 17(8): 1365-1382, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33559354

RESUMO

INTRODUCTION: Amyloid beta (Aß) oligomers are one of the most toxic structural forms of the Aß protein and are hypothesized to cause synaptotoxicity and memory failure as they build up in Alzheimer's disease (AD) patients' brain tissue. We previously demonstrated that antagonists of the sigma-2 receptor complex effectively block Aß oligomer toxicity. CT1812 is an orally bioavailable, brain penetrant small molecule antagonist of the sigma-2 receptor complex that appears safe and well tolerated in healthy elderly volunteers. We tested CT1812's effect on Aß oligomer pathobiology in preclinical AD models and evaluated CT1812's impact on cerebrospinal fluid (CSF) protein biomarkers in mild to moderate AD patients in a clinical trial (ClinicalTrials.gov NCT02907567). METHODS: Experiments were performed to measure the impact of CT1812 versus vehicle on Aß oligomer binding to synapses in vitro, to human AD patient post mortem brain tissue ex vivo, and in living APPSwe /PS1dE9 transgenic mice in vivo. Additional experiments were performed to measure the impact of CT1812 versus vehicle on Aß oligomer-induced deficits in membrane trafficking rate, synapse number, and protein expression in mature hippocampal/cortical neurons in vitro. The impact of CT1812 on cognitive function was measured in transgenic Thy1 huAPPSwe/Lnd+ and wild-type littermates. A multicenter, double-blind, placebo-controlled parallel group trial was performed to evaluate the safety, tolerability, and impact on protein biomarker expression of CT1812 or placebo given once daily for 28 days to AD patients (Mini-Mental State Examination 18-26). CSF protein expression was measured by liquid chromatography with tandem mass spectrometry or enzyme-linked immunosorbent assay in samples drawn prior to dosing (Day 0) and at end of dosing (Day 28) and compared within each patient and between pooled treated versus placebo-treated dosing groups. RESULTS: CT1812 significantly and dose-dependently displaced Aß oligomers bound to synaptic receptors in three independent preclinical models of AD, facilitated oligomer clearance into the CSF, increased synaptic number and protein expression in neurons, and improved cognitive performance in transgenic mice. CT1812 significantly increased CSF concentrations of Aß oligomers in AD patient CSF, reduced concentrations of synaptic proteins and phosphorylated tau fragments, and reversed expression of many AD-related proteins dysregulated in CSF. DISCUSSION: These preclinical studies demonstrate the novel disease-modifying mechanism of action of CT1812 against AD and Aß oligomers. The clinical results are consistent with preclinical data and provide evidence of target engagement and impact on fundamental disease-related signaling pathways in AD patients, supporting further development of CT1812.


Assuntos
Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Biomarcadores/líquido cefalorraquidiano , Cognição/efeitos dos fármacos , Camundongos Transgênicos , Receptores sigma/antagonistas & inibidores , Idoso , Animais , Encéfalo/metabolismo , Método Duplo-Cego , Ensaio de Imunoadsorção Enzimática , Hipocampo/metabolismo , Humanos , Masculino , Camundongos , Neurônios/metabolismo , Sinapses/metabolismo
9.
Crit Rev Food Sci Nutr ; 61(2): 283-311, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32090597

RESUMO

This review paper describes our exploratory experimental studies on the functionality of sucrose and other sugars in cake-baking, and effects on cake quality. We have used the American Association of Cereal Chemists Method 10-90.01 as a base cake-baking method, and have applied Differential Scanning Calorimetry, Rapid Visco-Analyzer, and time-lapse photography analyses in experimental design studies of the effects of the following ingredient and formulation variables on cake quality (e.g. texture, color, moisture content) and other finished-product properties (e.g. shape, dimensions): (a) cake formula levels of sucrose and water, in terms of %Sucrose and Total Solvent; (b) concentration of sucrose or other sugars (e.g. xylose, ribose, fructose, glucose, maltose, polydextrose) vs. wheat flour starch gelatinization temperature and starch pasting during baking and gluten development during mixing; (c) unchlorinated flour vs. chlorinated flours (of varying pH); (d) cake formula %Sucrose and TS vs. cake color, shape, and dimensions; (e) cakes formulated with sucrose or other sugars (i.e. xylose, fructose, glucose), and variable %S and TS, and unchlorinated or chlorinated flour (pH 4.6), vs. cake color, shape, and dimensions.


Assuntos
Farinha , Açúcares , Glutens , Amido , Triticum
10.
J Neurochem ; 157(4): 1316-1330, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33025581

RESUMO

Several mutations conferring protection against Alzheimer's disease (AD) have been described, none as profound as the A673T mutation, where carriers are four times less likely to get AD compared to noncarriers. This mutation results in reduced amyloid beta (Aß) protein production in vitro and lower lifetime Aß concentration in carriers. Better understanding of the protective mechanisms of the mutation may provide important insights into AD pathophysiology and identify productive therapeutic intervention strategies for disease modification. Aß(1-42) protein forms oligomers that bind saturably to a single receptor site on neuronal synapses, initiating the downstream toxicities observed in AD. Decreased formation, toxicity, or stability of soluble Aß oligomers, or reduction of synaptic binding of these oligomers, may combine with overall lower Aß concentration to underlie A673T's disease protecting mechanism. To investigate these possibilities, we compared the formation rate of soluble oligomers made from Icelandic A673T mutant and wild type (wt) Aß(1-42) synthetic protein, the amount and intensity of oligomer bound to mature primary rat hippocampal/cortical neuronal synapses, and the potency of bound oligomers to impact trafficking rate in neurons in vitro using a physiologically relevant oligomer preparation method. At equal protein concentrations, mutant protein forms approximately 50% or fewer oligomers of high molecular weight (>50 kDa) compared to wt protein. Mutant oligomers are twice as potent at altering the cellular vesicle trafficking rate as wt at equivalent concentrations, however, mutant oligomers have a >4-fold lower binding affinity to synaptic receptors (Kd  = 1,950 vs. 442 nM). The net effect of these differences is a lower overall toxicity at a given concentration. This study demonstrates for the first time that mutant A673T Aß oligomers prepared with this method have fundamentally different assembly characteristics and biological impact from wt protein and indicates that its disease protecting mechanism may result primarily from the mutant protein's much lower binding affinity to synaptic receptors. This suggests that therapeutics that effectively reduce oligomer binding to synapses in the brain may be beneficial in AD.


Assuntos
Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/genética , Peptídeos beta-Amiloides/metabolismo , Neurônios/metabolismo , Animais , Humanos , Ligação Proteica , Transporte Proteico/fisiologia , Ratos , Ratos Sprague-Dawley
11.
Phys Rev Lett ; 123(23): 230504, 2019 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-31868463

RESUMO

We demonstrate quantum many-body state reconstruction from experimental data generated by a programmable quantum simulator by means of a neural-network model incorporating known experimental errors. Specifically, we extract restricted Boltzmann machine wave functions from data produced by a Rydberg quantum simulator with eight and nine atoms in a single measurement basis and apply a novel regularization technique to mitigate the effects of measurement errors in the training data. Reconstructions of modest complexity are able to capture one- and two-body observables not accessible to experimentalists, as well as more sophisticated observables such as the Rényi mutual information. Our results open the door to integration of machine learning architectures with intermediate-scale quantum hardware.

12.
Phys Rev Lett ; 123(17): 170503, 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31702233

RESUMO

We report the implementation of universal two- and three-qubit entangling gates on neutral-atom qubits encoded in long-lived hyperfine ground states. The gates are mediated by excitation to strongly interacting Rydberg states and are implemented in parallel on several clusters of atoms in a one-dimensional array of optical tweezers. Specifically, we realize the controlled-phase gate, enacted by a novel, fast protocol involving only global coupling of two qubits to Rydberg states. We benchmark this operation by preparing Bell states with fidelity F≥95.0(2)%, and extract gate fidelity ≥97.4(3)%, averaged across five atom pairs. In addition, we report a proof-of-principle implementation of the three-qubit Toffoli gate, in which two control atoms simultaneously constrain the behavior of one target atom. These experiments demonstrate key ingredients for high-fidelity quantum information processing in a scalable neutral-atom platform.

13.
Drug Alcohol Depend ; 202: 13-17, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-31280002

RESUMO

INTRODUCTION: Due to the increase in people who use opioids in the US, there has been a steady increase in injection drug use. Without access to safe syringe disposal locations, people who inject drugs (PWID) have few options other than improper disposal, including in public places. In 2016, Florida's first legal Syringe Services Program (SSP) was established in Miami. This study aims to compare syringe disposal practices among PWID before and after the implementation of an SSP. METHODS: Visual inspection walkthroughs of randomly selected census blocks in the neighborhoods in the top quartile of narcotics-related arrests were conducted to assess improperly discarded syringes. Syringe location was geocoded in ArcGIS. Adult PWID pre-SSP (n = 448) and post-SSP (n = 482) implementation were recruited for a survey using respondent-driven sampling in Miami. A Poisson regression model was used to determine the adjusted relative risk (aRR) of improper syringe disposal pre- and post-SSP. RESULTS: A total of 191 syringes/1000 blocks were found post-implementation versus 371/1000 blocks pre-implementation, representing a 49% decrease after SSP implementation. In the surveys, 70% reported any improper syringe disposal post-SSP implementation versus 97% pre-SSP implementation. PWID in the post-implementation survey had 39% lower adjusted relative risk (aRR = 0.613; 95% CI = 0.546, 0.689) of improper syringe disposal as compared to pre-implementation. CONCLUSIONS: There was a significant decrease in the number of improperly discarded syringes in public in Miami after the implementation of an SSP. Providing PWID with proper disposal venues such as an SSP could decrease public disposal in other communities.


Assuntos
Usuários de Drogas/estatística & dados numéricos , Programas de Troca de Agulhas/estatística & dados numéricos , Seringas/estatística & dados numéricos , Adulto , Usuários de Drogas/psicologia , Feminino , Florida , Implementação de Plano de Saúde/estatística & dados numéricos , Humanos , Masculino , Distribuição de Poisson , Avaliação de Programas e Projetos de Saúde , Análise de Regressão , Características de Residência , Abuso de Substâncias por Via Intravenosa/psicologia , Inquéritos e Questionários
14.
Opt Lett ; 44(12): 3178-3181, 2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-31199410

RESUMO

In this Letter, to the best of our knowledge, we report a new method to generate uniform large-scale optical focus arrays (LOFAs). By identifying and removing undesired phase rotation in the iterative Fourier transform algorithm (IFTA), our approach rapidly produces computer-generated holograms of highly uniform LOFAs. The new algorithm also shows a faster compensation of system-induced LOFA intensity inhomogeneity than the conventional IFTA. After only three adaptive correction steps, we demonstrate LOFAs consisting of O(103) optical foci with an intensity uniformity greater than 98%.

15.
Nature ; 568(7751): 207-211, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30936552

RESUMO

Quantum phase transitions (QPTs) involve transformations between different states of matter that are driven by quantum fluctuations1. These fluctuations play a dominant part in the quantum critical region surrounding the transition point, where the dynamics is governed by the universal properties associated with the QPT. Although time-dependent phenomena associated with classical, thermally driven phase transitions have been extensively studied in systems ranging from the early Universe to Bose-Einstein condensates2-5, understanding critical real-time dynamics in isolated, non-equilibrium quantum systems remains a challenge6. Here we use a Rydberg atom quantum simulator with programmable interactions to study the quantum critical dynamics associated with several distinct QPTs. By studying the growth of spatial correlations when crossing the QPT, we experimentally verify the quantum Kibble-Zurek mechanism (QKZM)7-9 for an Ising-type QPT, explore scaling universality and observe corrections beyond QKZM predictions. This approach is subsequently used to measure the critical exponents associated with chiral clock models10,11, providing new insights into exotic systems that were not previously understood and opening the door to precision studies of critical phenomena, simulations of lattice gauge theories12,13 and applications to quantum optimization14,15.

16.
Phys Rev Lett ; 121(12): 123603, 2018 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-30296143

RESUMO

Individual neutral atoms excited to Rydberg states are a promising platform for quantum simulation and quantum information processing. However, experimental progress to date has been limited by short coherence times and relatively low gate fidelities associated with such Rydberg excitations. We report progress towards high-fidelity quantum control of Rydberg-atom qubits. Enabled by a reduction in laser phase noise, our approach yields a significant improvement in coherence properties of individual qubits. We further show that this high-fidelity control extends to the multi-particle case by preparing a two-atom entangled state with a fidelity exceeding 0.97(3), and extending its lifetime with a two-atom dynamical decoupling protocol. These advances open up new prospects for scalable quantum simulation and quantum computation with neutral atoms.

17.
Chemphyschem ; 19(22): 3001-3009, 2018 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-30183138

RESUMO

Two analogues to the fluorescent amyloid probe 2,5-bis(4'-hydroxy-3'-carboxy-styryl)benzene (X-34) were synthesized based on the trans-stilbene pyrene scaffold (Py1SA and Py2SA). The compounds show strikingly different emission spectra when bound to preformed Aß1-42 fibrils. This remarkable emission difference is retained when bound to amyloid fibrils of four distinct proteins, suggesting a common binding configuration for each molecule. Density functional theory calculations show that Py1SA is twisted, while Py2SA is more planar. Still, an analysis of the highest occupied molecular orbitals (HOMOs) and lowest unoccupied molecular orbitals (LUMOs) of the two compounds indicates that the degree of electronic coupling between the pyrene and salicylic acid (SA) moieties is larger in Py1SA than in Py2SA. Excited state intramolecular proton transfer (ESIPT) coupled-charge transfer (ICT) was observed for the anionic form in polar solvents. We conclude that ICT properties of trans-stilbene derivatives can be utilized for amyloid probe design with large changes in emission spectra and decay times from analogous chemical structures depending on the detailed physical nature of the binding site.


Assuntos
Peptídeos beta-Amiloides/química , Fragmentos de Peptídeos/química , Prótons , Pirenos/química , Salicilatos/química , Estilbenos/química , Teoria da Densidade Funcional , Fluorescência , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/química , Corantes Fluorescentes/efeitos da radiação , Luz , Modelos Químicos , Estrutura Molecular , Multimerização Proteica , Pirenos/síntese química , Pirenos/efeitos da radiação , Salicilatos/síntese química , Salicilatos/efeitos da radiação , Estilbenos/síntese química , Estilbenos/efeitos da radiação
18.
Chemistry ; 24(28): 7210-7216, 2018 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-29543355

RESUMO

We revisited the Congo red analogue 2,5-bis(4'-hydroxy-3'-carboxy-styryl)benzene (X-34) to develop this highly fluorescent amyloid dye for imaging Alzheimer's disease (AD) pathology comprising Aß and Tau fibrils. A selection of ligands with distinct optical properties were synthesized by replacing the central benzene unit of X-34, with other heterocyclic moieties. Full photophysical characterization was performed, including recording absorbance and fluorescence spectra, Stokes shift, quantum yield and fluorescence lifetimes. All ligands displayed high affinity towards recombinant amyloid fibrils of Aß1-42 (13-300 nm Kd ) and Tau (16-200 nm Kd ) as well as selectivity towards the corresponding disease-associated protein aggregates in AD tissue. We observed that these ligands efficiently displaced X-34, but not Pittsburgh compound B (PiB) from recombinant Aß1-42 amyloid fibrils, arguing for retained targeting of the Congo red type binding site. We foresee that the X-34 scaffold offers the possibility to develop novel high-affinity ligands for Aß pathology found in human AD brain in a different mode compared with PiB, potentially recognizing different polymorphs of Aß fibrils.


Assuntos
Alcenos/química , Peptídeos beta-Amiloides/química , Amiloide/química , Amiloide/metabolismo , Compostos de Anilina/química , Benzoatos/química , Corantes Fluorescentes/química , Tiazóis/química , Proteínas tau/química , Peptídeos beta-Amiloides/metabolismo , Humanos
19.
Crit Rev Food Sci Nutr ; 58(6): 972-992, 2018 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-27657744

RESUMO

This article reviews the application of the "Food Polymer Science" approach to the practice of industrial R&D, leading to patent estates based on fundamental starch science and technology. The areas of patents and patented technologies reviewed here include: (a) soft-from-the-freezer ice creams and freezer-storage-stable frozen bread dough products, based on "cryostabilization technology" of frozen foods, utilizing commercial starch hydrolysis products (SHPs); (b) glassy-matrix encapsulation technology for flavors and other volatiles, based on structure-function relationships for commercial SHPs;


Assuntos
Tecnologia de Alimentos , Polímeros/química , Amido/química , Farinha/análise , Aditivos Alimentares/química , Manipulação de Alimentos , Qualidade dos Alimentos , Relação Estrutura-Atividade , Triticum/química
20.
Nature ; 551(7682): 579-584, 2017 11 29.
Artigo em Inglês | MEDLINE | ID: mdl-29189778

RESUMO

Controllable, coherent many-body systems can provide insights into the fundamental properties of quantum matter, enable the realization of new quantum phases and could ultimately lead to computational systems that outperform existing computers based on classical approaches. Here we demonstrate a method for creating controlled many-body quantum matter that combines deterministically prepared, reconfigurable arrays of individually trapped cold atoms with strong, coherent interactions enabled by excitation to Rydberg states. We realize a programmable Ising-type quantum spin model with tunable interactions and system sizes of up to 51 qubits. Within this model, we observe phase transitions into spatially ordered states that break various discrete symmetries, verify the high-fidelity preparation of these states and investigate the dynamics across the phase transition in large arrays of atoms. In particular, we observe robust many-body dynamics corresponding to persistent oscillations of the order after a rapid quantum quench that results from a sudden transition across the phase boundary. Our method provides a way of exploring many-body phenomena on a programmable quantum simulator and could enable realizations of new quantum algorithms.

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