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1.
Chem Senses ; 492024 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-38421250

RESUMO

Many common chemotherapeutics produce disruptions in the sense of taste which can lead to loss of appetite, nutritional imbalance, and reduced quality of life, especially if taste loss persists after treatment ends. Cyclophosphamide (CYP), an alkylating chemotherapeutic agent, affects taste sensitivity through its cytotoxic effects on mature taste receptor cells (TRCs) and on taste progenitor cell populations, retarding the capacity to replace TRCs. Mechanistic studies have focused primarily on taste cells, however, taste signaling requires communication between TRCs and the gustatory nerve fibers that innervate them. Here, we evaluate cyclophosphamide's effects on the peripheral gustatory nerve fibers that innervate the taste buds. Following histological analysis of tongue tissues, we find that CYP reduces innervation within the fungiform and circumvallates taste buds within 4 days after administration. To better understand the dynamics of the denervation process, we used 2-photon intravital imaging to visualize the peripheral gustatory nerve fibers within individual fungiform taste buds up to 20 days after CYP treatment. We find that gustatory fibers retract from the taste bud properly but are maintained within the central papilla core. These data indicate that in addition to TRCs, gustatory nerve fibers are also affected by CYP treatment. Because the connectivity between TRCs and gustatory neurons must be re-established for proper function, gustatory fibers should continue to be included in future studies to understand the mechanisms leading to chemotherapy-induced persistent taste loss.


Assuntos
Ageusia , Papilas Gustativas , Animais , Camundongos , Papilas Gustativas/fisiologia , Qualidade de Vida , Língua , Ciclofosfamida/farmacologia , Paladar
2.
J Neurophysiol ; 131(2): 321-337, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38198656

RESUMO

There is a lack of experimental methods in genetically tractable mouse models to analyze the developmental period at which newborns mature weight-bearing locomotion. To overcome this deficit, we introduce methods to study l-3,4-dihydroxyphenylalanine (l-DOPA)-induced air-stepping in mice at postnatal day (P)7 and P10. Air-stepping is a stereotypic rhythmic behavior that resembles mouse walking overground locomotion but without constraints imposed by weight bearing, postural adjustments, or sensory feedback. We propose that air-stepping represents the functional organization of early spinal circuits coordinating limb movements. After subcutaneous injection of l-DOPA (0.5 mg/g), we recorded air-stepping movements in all four limbs and electromyographic (EMG) activity from ankle flexor (tibialis anterior, TA) and extensor (lateral gastrocnemius, LG) muscles. Using DeepLabCut pose estimation, we analyzed rhythmicity and limb coordination. We demonstrate steady rhythmic stepping of similar duration from P7 to P10 but with some fine-tuning of interlimb coordination with age. Hindlimb joints undergo a greater range of flexion at older ages, indicating maturation of flexion-extension cycles as the animal starts to walk. EMG recordings of TA and LG show alternation but with more focused activation particularly in the LG from P7 to P10. We discuss similarities to neonatal rat l-DOPA-induced air-stepping and infant assisted walking. We conclude that limb coordination and muscle activations recorded with this method represent basic spinal cord circuitry for limb control in neonates and pave the way for future investigations on the development of rhythmic limb control in genetic or disease models with correctly or erroneously developing motor circuitry.NEW & NOTEWORTHY We present novel methods to study neonatal air-stepping in newborn mice. These methods allow analyses at the onset of limb coordination during the period in which altricial species like rats, mice, and humans "learn" to walk. The methods will be useful to test a large variety of mutations that serve as models of motor disease in newborns or that are used to probe for specific circuit mechanisms that generate coordinated limb motor output.


Assuntos
Levodopa , Músculo Esquelético , Recém-Nascido , Animais , Ratos , Camundongos , Humanos , Animais Recém-Nascidos , Levodopa/farmacologia , Eletromiografia , Músculo Esquelético/fisiologia , Movimento , Locomoção/fisiologia , Membro Posterior/fisiologia
3.
Sci Adv ; 10(3): eadj4960, 2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38232174

RESUMO

Revolutionary advancements in underwater imaging, robotics, and genomic sequencing have reshaped marine exploration. We present and demonstrate an interdisciplinary approach that uses emerging quantitative imaging technologies, an innovative robotic encapsulation system with in situ RNA preservation and next-generation genomic sequencing to gain comprehensive biological, biophysical, and genomic data from deep-sea organisms. The synthesis of these data provides rich morphological and genetic information for species description, surpassing traditional passive observation methods and preserved specimens, particularly for gelatinous zooplankton. Our approach enhances our ability to study delicate mid-water animals, improving research in the world's oceans.


Assuntos
Robótica , Zooplâncton , Animais , Oceanos e Mares , Zooplâncton/genética , Água , Gelatina
4.
JAMA Netw Open ; 5(4): e228855, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-35467731

RESUMO

Importance: The COVID-19 pandemic has impacted cancer systems worldwide. Quantifying the changes is critical to informing the delivery of care while the pandemic continues, as well as for system recovery and future pandemic planning. Objective: To quantify change in the delivery of cancer services across the continuum of care during the COVID-19 pandemic. Design, Setting, and Participants: This population-based cohort study assessed cancer screening, imaging, diagnostic, treatment, and psychosocial oncological care services delivered in pediatric and adult populations in Ontario, Canada (population 14.7 million), from April 1, 2019, to March 1, 2021. Data were analyzed from May 1 to July 31, 2021. Exposures: COVID-19 pandemic. Main Outcomes and Measures: Cancer service volumes from the first year of the COVID-19 pandemic, defined as April 1, 2020, to March 31, 2021, were compared with volumes during a prepandemic period of April 1, 2019, to March 31, 2020. Results: During the first year of the pandemic, there were a total of 4 476 693 cancer care services, compared with 5 644 105 services in the year prior, a difference of 20.7% fewer services of cancer care, representing a potential backlog of 1 167 412 cancer services. While there were less pronounced changes in systemic treatments, emergency and urgent imaging examinations (eg, 1.9% more parenteral systemic treatments) and surgical procedures (eg, 65% more urgent surgical procedures), major reductions were observed for most services beginning in March 2020. Compared with the year prior, during the first pandemic year, cancer screenings were reduced by 42.4% (-1 016 181 screening tests), cancer treatment surgical procedures by 14.1% (-8020 procedures), and radiation treatment visits by 21.0% (-141 629 visits). Biopsies to confirm cancer decreased by up to 41.2% and surgical cancer resections by up to 27.8% during the first pandemic wave. New consultation volumes also decreased, such as for systemic treatment (-8.2%) and radiation treatment (-9.3%). The use of virtual cancer care increased for systemic treatment and radiation treatment and psychosocial oncological care visits, increasing from 0% to 20% of total new or follow-up visits prior to the pandemic up to 78% of total visits in the first pandemic year. Conclusions and Relevance: In this population-based cohort study in Ontario, Canada, large reductions in cancer service volumes were observed. While most services recovered to prepandemic levels at the end of the first pandemic year, a substantial care deficit likely accrued. The anticipated downstream morbidity and mortality associated with this deficit underscore the urgent need to address the backlog and recover cancer care and warrant further study.


Assuntos
COVID-19 , Influenza Humana , Neoplasias , Adulto , COVID-19/epidemiologia , Criança , Estudos de Coortes , Humanos , Influenza Humana/prevenção & controle , Neoplasias/epidemiologia , Neoplasias/terapia , Ontário/epidemiologia , Pandemias
5.
Top Cogn Sci ; 14(4): 739-755, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-34529347

RESUMO

The fields of machine learning (ML) and cognitive science have developed complementary approaches to computationally modeling human behavior. ML's primary concern is maximizing prediction accuracy; cognitive science's primary concern is explaining the underlying mechanisms. Cross-talk between these disciplines is limited, likely because the tasks and goals usually differ. The domain of e-learning and knowledge acquisition constitutes a fruitful intersection for the two fields' methodologies to be integrated because accurately tracking learning and forgetting over time and predicting future performance based on learning histories are central to developing effective, personalized learning tools. Here, we show how a state-of-the-art ML model can be enhanced by incorporating insights from a cognitive model of human memory. This was done by exploiting the predictive performance equation's (PPE) narrow but highly specialized domain knowledge with regard to the temporal dynamics of learning and forgetting. Specifically, the PPE was used to engineer timing-related input features for a gradient-boosted decision trees (GBDT) model. The resulting PPE-enhanced GBDT outperformed the default GBDT, especially under conditions in which limited data were available for training. Results suggest that integrating cognitive and ML models could be particularly productive if the available data are too high-dimensional to be explained by a cognitive model but not sufficiently large to effectively train a modern ML algorithm. Here, the cognitive model's insights pertaining to only one aspect of the data were enough to jump-start the ML model's ability to make predictions-a finding that holds promise for future explorations.


Assuntos
Cognição , Aprendizado de Máquina , Humanos , Previsões , Algoritmos
6.
Psychol Rep ; 125(1): 129-147, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33174817

RESUMO

Psychologists have debated the wisdom of recovering traumatic memories in therapy that were previously unknown to the client, with some concerns over accuracy and memory distortions. The current study surveyed a sample of 576 undergraduates in the south of the United States. Of 188 who reported attending therapy or counselling, 8% reported coming to remember memories of abuse, without any prior recollection of that abuse before therapy. Of those who reported recovered memories, 60% cut off contact with some of their family. Within those who received therapy, those who had a therapist discuss the possibility of repressed memory were 28.6 times more likely to report recovered memories, compared to those who received therapy without such discussion. These findings mirror a previous survey of US adults and suggest attempts to recover repressed memories in therapy may continue in the forthcoming generation of adults.


Assuntos
Abuso Sexual na Infância , Repressão Psicológica , Adulto , Criança , Humanos , Rememoração Mental , Estudantes , Inquéritos e Questionários , Estados Unidos
7.
Proc Natl Acad Sci U S A ; 118(49)2021 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-34845027

RESUMO

Quantum coherences, observed as time-dependent beats in ultrafast spectroscopic experiments, arise when light-matter interactions prepare systems in superpositions of states with differing energy and fixed phase across the ensemble. Such coherences have been observed in photosynthetic systems following ultrafast laser excitation, but what these coherences imply about the underlying energy transfer dynamics remains subject to debate. Recent work showed that redox conditions tune vibronic coupling in the Fenna-Matthews-Olson (FMO) pigment-protein complex in green sulfur bacteria, raising the question of whether redox conditions may also affect the long-lived (>100 fs) quantum coherences observed in this complex. In this work, we perform ultrafast two-dimensional electronic spectroscopy measurements on the FMO complex under both oxidizing and reducing conditions. We observe that many excited-state coherences are exclusively present in reducing conditions and are absent or attenuated in oxidizing conditions. Reducing conditions mimic the natural conditions of the complex more closely. Further, the presence of these coherences correlates with the vibronic coupling that produces faster, more efficient energy transfer through the complex under reducing conditions. The growth of coherences across the waiting time and the number of beating frequencies across hundreds of wavenumbers in the power spectra suggest that the beats are excited-state coherences with a mostly vibrational character whose phase relationship is maintained through the energy transfer process. Our results suggest that excitonic energy transfer proceeds through a coherent mechanism in this complex and that the coherences may provide a tool to disentangle coherent relaxation from energy transfer driven by stochastic environmental fluctuations.


Assuntos
Transferência de Energia/fisiologia , Complexos de Proteínas Captadores de Luz/fisiologia , Fotossíntese/fisiologia , Proteínas de Bactérias/química , Luz , Complexos de Proteínas Captadores de Luz/metabolismo , Oxirredução , Complexo de Proteínas do Centro de Reação Fotossintética/fisiologia , Pigmentação , Teoria Quântica , Análise Espectral/métodos , Vibração
8.
J Exp Orthop ; 8(1): 95, 2021 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-34677691

RESUMO

PURPOSE: A large percentage of anterior cruciate ligament (ACL) surgical reconstructions experience sub-optimal outcomes within 2 years. A potential factor contributing to poor outcomes is an incomplete understanding of micro-level, regional ACL biomechanics. This research aimed to demonstrate a minimally invasive method that uses micro-CT imaging to quantify regional ACL strains under clinically relevant joint loading. METHODS: A pattern of 0.8 mm diameter zirconium dioxide beads were arthroscopically inserted into four regions of the ACL of four cadaveric knee specimens (mean [SD] age = 59 [9] years). A custom micro-CT compatible joint motion simulator then applied clinically relevant joint loading conditions, while an image was acquired at each condition. From the resulting images, strains within each region were calculated using the centroid coordinates of each tissue-embedded bead. Strain repeatability was assessed using the mean intra-specimen standard deviation across repeated load applications. A one-way repeated measures ANOVA (α = 0.05) was used to determine regional strain variations. RESULTS: The mean intra-specimen standard deviation across repeated load application was ±0.003 strain for all specimens. No statistically significant differences were found between tissue regions, although medium and large effect sizes (0.095-0.450) suggest that these differences may be clinically relevant. CONCLUSIONS: The method presented here demonstrates a minimally invasive measurement of regional ACL strain under clinically relevant joint loads using micro-CT imaging. The strain measurements demonstrated excellent reliability across the five repeated load applications and suggest a non-homogenous distribution of strain through the ACL.

9.
Biology (Basel) ; 10(8)2021 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-34439946

RESUMO

DGAT2 is a transmembrane protein encoded by the DGAT2 gene that functions in lipid metabolism, triacylglycerol synthesis, and lipid droplet regulation. Cancer cells exhibit altered lipid metabolism and mutations in DGAT2 may contribute to this state. Using data from the Catalogue of Somatic Mutations in Cancer (COSMIC), we analyzed all cancer genetic DGAT2 alterations, including mutations, copy number variations and gene expression. We find that several DGAT2 mutations fall within the catalytic site of the enzyme. Using the Variant Effect Scoring Tool (VEST), we identify multiple mutations with a high likelihood of contributing to cellular transformation. We also found that D222V is a mutation hotspot neighboring a previously discovered Y223H mutation that causes Axonal Charcot-Marie-Tooth disease. Remarkably, Y223H has not been detected in cancers, suggesting that it is inhibitory to cancer progression. We also identify several single nucleotide polymorphisms (SNP) with high VEST scores, indicating that certain alleles in human populations have a pathogenic predisposition. Most mutations do not correlate with a change in gene expression, nor is gene expression dependent on high allele copy number. However, we did identify eight alleles with high expression levels, suggesting that at least in certain cases, the excess DGAT2 gene product is not inhibitory to cellular proliferation. This work uncovers unknown functions of DGAT2 in cancers and suggests that its role may be more complex than previously appreciated.

10.
ACS Nano ; 15(6): 10253-10263, 2021 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-34096707

RESUMO

The valley pseudospin at the K and K' high-symmetry points in monolayer transition metal dichalcogenides (TMDs) has potential as an optically addressable degree of freedom in next-generation optoelectronics. However, intervalley scattering and relaxation of charge carriers leads to valley depolarization and limits practical applications. In addition, enhanced Coulomb interactions lead to pronounced excitonic effects that dominate the optical response and initial valley depolarization dynamics but complicate the interpretation of ultrafast spectroscopic experiments at short time delays. Employing broadband helicity-resolved two-dimensional electronic spectroscopy (2DES), we observe ultrafast (∼10 fs) intervalley coupling between all A and B valley exciton states that results in a complete breakdown of the valley index in large-area monolayer MoS2 films. These couplings and subsequent dynamics exhibit minimal excitation fluence or temperature dependence and are robust toward changes in sample grain size and inherent strain. Our observations strongly suggest that this direct intervalley coupling on the time scale of optical excitation is an inherent property of large-area MoS2 distinct from dynamic carrier or exciton scattering, phonon-driven processes, and multiexciton effects. This ultrafast intervalley coupling poses a fundamental challenge for exciton-based valleytronics in monolayer TMDs and must be overcome to fully realize large-area valleytronic devices.

11.
Proc Natl Acad Sci U S A ; 118(11)2021 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-33688046

RESUMO

Photosynthetic species evolved to protect their light-harvesting apparatus from photoxidative damage driven by intracellular redox conditions or environmental conditions. The Fenna-Matthews-Olson (FMO) pigment-protein complex from green sulfur bacteria exhibits redox-dependent quenching behavior partially due to two internal cysteine residues. Here, we show evidence that a photosynthetic complex exploits the quantum mechanics of vibronic mixing to activate an oxidative photoprotective mechanism. We use two-dimensional electronic spectroscopy (2DES) to capture energy transfer dynamics in wild-type and cysteine-deficient FMO mutant proteins under both reducing and oxidizing conditions. Under reducing conditions, we find equal energy transfer through the exciton 4-1 and 4-2-1 pathways because the exciton 4-1 energy gap is vibronically coupled with a bacteriochlorophyll-a vibrational mode. Under oxidizing conditions, however, the resonance of the exciton 4-1 energy gap is detuned from the vibrational mode, causing excitons to preferentially steer through the indirect 4-2-1 pathway to increase the likelihood of exciton quenching. We use a Redfield model to show that the complex achieves this effect by tuning the site III energy via the redox state of its internal cysteine residues. This result shows how pigment-protein complexes exploit the quantum mechanics of vibronic coupling to steer energy transfer.


Assuntos
Proteínas de Bactérias/química , Transferência de Energia , Complexos de Proteínas Captadores de Luz/química , Fotossíntese , Teoria Quântica , Proteínas de Bactérias/genética , Cisteína/química , Complexos de Proteínas Captadores de Luz/genética , Oxirredução , Análise Espectral/métodos , Vibração
12.
J Biomech ; 115: 110133, 2021 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-33257006

RESUMO

Clinical outcomes following posterior cruciate ligament (PCL) reconstruction are often suboptimal. A better understanding of the biomechanical contributions of the PCL to knee stability under physiologic, clinically-relevant loading conditions could improve reconstruction techniques and outcomes. We employed a servohydraulic joint motion simulator to investigate the kinematics of intact and PCL-deficient knees during simulated clinical tests and activities of daily living(ADL), including gait, stair ascent and descent. PCL transection caused the tibia to be displaced posterior, relative to the intact joint, throughout flexion. PCL transection also increased the amount of posterior tibial displacement measured during posterior laxity testing by up to 9.6 ± 1.7 mm at 75° (p = 0.001). During internal-external rotational laxity testing, PCL transection increased the allowable internal and external rotation of the tibia, by up to 2.9 ± 0.5°at90° (p = 0.001) and 1.0 ± 0.2° at45°(p = 0.001), respectively. PCL transection did not have a significant effect on abduction-adduction kinematics or laxity, regardless of flexion angle. PCL transection resulted in a relative posterior displacement of the tibia during the stance phase of gait when the knee was extended (2.2 ± 2.2 mm, p = 0.045), and when the knee was flexed during stair ascent (2.4 ± 2.2 mm, p = 0.035) and descent (1.6 ± 1.4 mm, p = 0.037). Our results support previous studies of the role of the PCL on neutral joint kinematics and laxity, and provide new data quantifying the effect of PCL transection on AP kinematics during simulated ADL.


Assuntos
Instabilidade Articular , Ligamento Cruzado Posterior , Atividades Cotidianas , Fenômenos Biomecânicos , Cadáver , Humanos , Joelho , Articulação do Joelho , Amplitude de Movimento Articular , Rotação , Tíbia
13.
Opt Express ; 28(22): 32869-32881, 2020 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-33114962

RESUMO

Phase stability between pulse pairs defining Fourier-transform time delays can limit resolution and complicates development and adoption of multidimensional coherent spectroscopies. We demonstrate a data processing procedure to correct the long-term phase drift of the nonlinear signal during two-dimensional (2D) experiments based on the relative phase between scattered excitation pulses and a global phasing procedure to generate fully absorptive 2D electronic spectra of wafer-scale monolayer MoS2. Our correction results in a ∼30-fold increase in effective long-term signal phase stability, from ∼λ/2 to ∼λ/70 with negligible extra experimental time and no additional optical components. This scatter-based drift correction should be applicable to other interferometric techniques as well, significantly lowering the practical experimental requirements for this class of measurements.

14.
J Dev Biol ; 8(3)2020 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-32660129

RESUMO

The skeletal system plays an important role in the development and maturation process. Through the bone remodeling process, 10% of the skeletal system is renewed every year. Osteoblasts and osteoclasts are two major bone cells that are involved in the development of the skeletal system, and their activity is kept in balance. An imbalance between their activities can lead to diseases such as osteoporosis that are characterized by significant bone loss due to the overactivity of bone-resorbing osteoclasts. Our laboratory has developed a novel peptide, CK2.3, which works as both an anabolic and anti-resorptive agent to induce bone formation and prevent bone loss. We previously reported that CK2.3 mediated mineralization and osteoblast development through the SMAD, ERK, and AKT signaling pathways. In this study, we demonstrated the mechanism by which CK2.3 inhibits osteoclast development. We showed that the inhibition of MEK by the U0126 inhibitor rescued the osteoclast development of RAW264.7 induced by RANKL in a co-culture system with CK2.3. We observed that CK2.3 induced ERK activation and BMPRIa expression on Day 1 after stimulation with CK2.3. While CK2.3 was previously reported to induce the SMAD signaling pathway in osteoblast development, we did not observe any changes in SMAD activation in osteoclast development with CK2.3 stimulation. Understanding the mechanism by which CK2.3 inhibits osteoclast development will allow CK2.3 to be developed as a new treatment for osteoporosis.

15.
J Alzheimers Dis ; 76(2): 613-621, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32538852

RESUMO

BACKGROUND: Previous studies indicate that taste dysfunction occurs early in the development of Alzheimer's disease. It is debatable whether the deficit in taste is due primarily to peripheral sensory mechanisms or to central processing, or a combination of the two. OBJECTIVE: The aim of our current study is to combine behavior and histological data in APP/PS1 transgenic mice to determine whether APP/PS1 transgenic mice show deficits in unconditioned taste preference and avoidance behaviors and whether taste impairments are due to defects in the peripheral taste system and/or problems with central processing of taste information. METHODS: The APP/PS1 transgenic mutant mice were used as a model of Alzheimer's disease. We employed a brief-access gustometer test to assess immediate orosensory taste responses of APP/PS1 mice. We used immunohistochemistry to examine tongue, gustatory ganglion, and brain tissues to determine a cytological basis for behavioral deficits. RESULTS: There is a significant, selective reduction of bitter taste sensitivity in APP/PS1 mice. These mice also have a loss of TRPM5-expressing taste receptor cells in the circumvallate papillae of the tongue. While we observed no overt loss of neuron cell bodies within the primary gustatory sensory neurons, degeneration of the neurons' peripheral axons innervating the taste bud may play a role in the observed loss of TRPM5-expressing taste receptor cells. CONCLUSION: This data supports a potential role for peripheral taste dysfunction in AD through the selective loss of taste receptor cells. Further study is necessary to delineate the mechanisms and pathological significance of this deficit in AD.


Assuntos
Precursor de Proteína beta-Amiloide/genética , Mutação/genética , Presenilina-1/genética , Distúrbios do Paladar/genética , Paladar/genética , Animais , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Camundongos , Camundongos Transgênicos , Quinina/administração & dosagem , Sacarose/administração & dosagem , Canais de Cátion TRPM/deficiência , Canais de Cátion TRPM/genética , Paladar/efeitos dos fármacos , Distúrbios do Paladar/fisiopatologia
16.
J Phys Chem Lett ; 11(10): 4163-4172, 2020 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-32391695

RESUMO

DNA scaffolds enable base-pair-specific positioning of fluorescent molecules, allowing for nanometer-scale precision in controlling multidye interactions. Expanding on this concept, DNA-based molecular photonic wires (MPWs) allow for light harvesting and directional propagation of photonic energy on the nanometer scale. The most common MPW examples exploit Förster resonance energy transfer (FRET), and FRET between the same dye species (HomoFRET) was recently shown to increase the distance and efficiency at which MPWs can function. Although increased proximity between adjacent fluorophores can be used to increase the energy transfer efficiency, FRET assumptions break down as the distance between the dye molecules becomes comparable to their size (∼2 nm). Here we compare dye conjugation with single versus dimer Cy5 dye repeats as HomoFRET MPW components on a double-crossover DNA scaffold. At room temperature (RT) under low-light conditions, end-labeled uncoupled dye molecules provide optimal transfer, while the Cy5 dimers show ultrafast (<100 ps) nonradiative decay that severely limits their functionality. Of particular interest is the observation that through increased excitation fluence as well as cryogenic temperatures, the dimeric MPW shows suppression of the ultrafast decay, demonstrating fluorescence lifetimes similar to the single Cy5 MPWs. This work points to the complex dynamic capabilities of dye-based nanophotonic networks, where dye positioning and interactions can become critical, and could be used to extend the lengths and complexities of such dye-DNA devices, enabling multiparameter nanophotonic circuitry.


Assuntos
Carbocianinas/química , DNA/química , Corantes Fluorescentes/química , Fótons , Termodinâmica , Transferência Ressonante de Energia de Fluorescência
17.
Front Microbiol ; 11: 257, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32153541

RESUMO

Bacterial antibiotic resistance is becoming a significant health threat, and rapid identification of antibiotic-resistant bacteria is essential to save lives and reduce the spread of antibiotic resistance. This paper analyzes the ability of machine learning algorithms (MLAs) to process data from a novel spectroscopic diagnostic device to identify antibiotic-resistant genes and bacterial species by comparison to available bacterial DNA sequences. Simulation results show that the algorithms attain from 92% accuracy (for genes) up to 99% accuracy (for species). This novel approach identifies genes and species by optically reading the percentage of A, C, G, T bases in 1000s of short 10-base DNA oligomers instead of relying on conventional DNA sequencing in which the sequence of bases in long oligomers provides genetic information. The identification algorithms are robust in the presence of simulated random genetic mutations and simulated random experimental errors. Thus, these algorithms can be used to identify bacterial species, to reveal antibiotic resistance genes, and to perform other genomic analyses. Some MLAs evaluated here are shown to be better than others at accurate gene identification and avoidance of false negative identification of antibiotic resistance.

18.
J Phys Chem Lett ; 11(7): 2658-2666, 2020 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-32168454

RESUMO

Transition-metal dichalcogenides (TMDs) such as MoS2 display promising electrical and optical properties in the monolayer limit. Due to strong quantum confinement, TMDs provide an ideal environment for exploring excitonic physics using ultrafast spectroscopy. However, the interplay between collective excitation effects on single excitons such as band gap renormalization/exciton binding energy (BGR/EBE) change and multiexciton effects such biexciton formation remains poorly understood. Using two-dimensional electronic spectroscopy, we observe the dominance of single-exciton BGR/EBE signals over optically induced biexciton formation. We make this determination based on a lack of strong PIA features at T = 0 fs in the cryogenic spectra. By means of nodal line slope analysis, we determine that spectral diffusion occurs faster than BGR/EBE change, indicative of distinct processes. These results indicate that at higher sub-Mott limit fluences, collective effects on single excitons dominate biexciton formation.

19.
Chem Sci ; 11(32): 8546-8557, 2020 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-34123114

RESUMO

Vibronic coupling between pigment molecules is believed to prolong coherences in photosynthetic pigment-protein complexes. Reproducing long-lived coherences using vibronically coupled chromophores in synthetic DNA constructs presents a biomimetic route to efficient artificial light harvesting. Here, we present two-dimensional (2D) electronic spectra of one monomeric Cy5 construct and two dimeric Cy5 constructs (0 bp and 1 bp between dyes) on a DNA scaffold and perform beating frequency analysis to interpret observed coherences. Power spectra of quantum beating signals of the dimers reveal high frequency oscillations that correspond to coherences between vibronic exciton states. Beating frequency maps confirm that these oscillations, 1270 cm-1 and 1545 cm-1 for the 0-bp dimer and 1100 cm-1 for the 1-bp dimer, are coherences between vibronic exciton states and that these coherences persist for ∼300 fs. Our observations are well described by a vibronic exciton model, which predicts the excitonic coupling strength in the dimers and the resulting molecular exciton states. The energy spacing between those states closely corresponds to the observed beat frequencies. MD simulations indicate that the dyes in our constructs lie largely internal to the DNA base stacking region, similar to the native design of biological light harvesting complexes. Observed coherences persist on the timescale of photosynthetic energy transfer yielding further parallels to observed biological coherences, establishing DNA as an attractive scaffold for synthetic light harvesting applications.

20.
Biotechnol Prog ; 36(1): e2892, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31425635

RESUMO

Rapid diagnosis of blood infections requires fast and efficient separation of bacteria from blood. We have developed spinning hollow disks that separate bacteria from blood cells via the differences in sedimentation velocities of these particles. Factors affecting separation included the spinning speed and duration, and disk size. These factors were varied in dozens of experiments for which the volume of separated plasma, and the concentration of bacteria and red blood cells (RBCs) in separated plasma were measured. Data were correlated by a parameter of characteristic sedimentation length, which is the distance that an idealized RBC would travel during the entire spin. Results show that characteristic sedimentation length of 20 to 25 mm produces an optimal separation and collection of bacteria in plasma. This corresponds to spinning a 12-cm-diameter disk at 3,000 rpm for 13 s. Following the spin, a careful deceleration preserves the separation of cells from plasma and provides a bacterial recovery of about 61 ± 5%.


Assuntos
Centrifugação , Eritrócitos/microbiologia , Escherichia coli/isolamento & purificação , Humanos , Tamanho da Partícula
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