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1.
Nature ; 598(7882): 590-596, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34671167

RESUMEN

Although solid-state lithium (Li)-metal batteries promise both high energy density and safety, existing solid ion conductors fail to satisfy the rigorous requirements of battery operations. Inorganic ion conductors allow fast ion transport, but their rigid and brittle nature prevents good interfacial contact with electrodes. Conversely, polymer ion conductors that are Li-metal-stable usually provide better interfacial compatibility and mechanical tolerance, but typically suffer from inferior ionic conductivity owing to the coupling of the ion transport with the motion of the polymer chains1-3. Here we report a general strategy for achieving high-performance solid polymer ion conductors by engineering of molecular channels. Through the coordination of copper ions (Cu2+) with one-dimensional cellulose nanofibrils, we show that the opening of molecular channels within the normally ion-insulating cellulose enables rapid transport of Li+ ions along the polymer chains. In addition to high Li+ conductivity (1.5 × 10-3 siemens per centimetre at room temperature along the molecular chain direction), the Cu2+-coordinated cellulose ion conductor also exhibits a high transference number (0.78, compared with 0.2-0.5 in other polymers2) and a wide window of electrochemical stability (0-4.5 volts) that can accommodate both the Li-metal anode and high-voltage cathodes. This one-dimensional ion conductor also allows ion percolation in thick LiFePO4 solid-state cathodes for application in batteries with a high energy density. Furthermore, we have verified the universality of this molecular-channel engineering approach with other polymers and cations, achieving similarly high conductivities, with implications that could go beyond safe, high-performance solid-state batteries.

2.
Nat Mater ; 22(12): 1531-1539, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37932334

RESUMEN

Liquid electrolytes in batteries are typically treated as macroscopically homogeneous ionic transport media despite having a complex chemical composition and atomistic solvation structures, leaving a knowledge gap of the microstructural characteristics. Here, we reveal a unique micelle-like structure in a localized high-concentration electrolyte, in which the solvent acts as a surfactant between an insoluble salt in a diluent. The miscibility of the solvent with the diluent and simultaneous solubility of the salt results in a micelle-like structure with a smeared interface and an increased salt concentration at the centre of the salt-solvent clusters that extends the salt solubility. These intermingling miscibility effects have temperature dependencies, wherein a typical localized high-concentration electrolyte peaks in localized cluster salt concentration near room temperature and is used to form a stable solid-electrolyte interphase on a Li metal anode. These findings serve as a guide to predicting a stable ternary phase diagram and connecting the electrolyte microstructure with electrolyte formulation and formation protocols of solid-electrolyte interphases for enhanced battery cyclability.

3.
J Am Chem Soc ; 145(4): 2473-2484, 2023 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-36689617

RESUMEN

Electrolytes, consisting of salts, solvents, and additives, must form a stable solid electrolyte interphase (SEI) to ensure the performance and durability of lithium(Li)-ion batteries. However, the electric double layer (EDL) structure near charged surfaces is still unsolved, despite its importance in dictating the species being reduced for SEI formation near a negative electrode. In this work, a newly developed model was used to illustrate the effect of EDL on SEI formation in two essential electrolytes, the carbonate-based electrolyte for Li-ion batteries and the ether-based electrolyte for batteries with Li-metal anodes. Both electrolytes have fluoroethylene carbonate (FEC) as a common additive to form the beneficial F-containing SEI component (e.g., LiF). However, the role of FEC drastically differs in these electrolytes. FEC is an effective SEI modifier for the carbonate-based electrolyte by being the only F-containing species entering the EDL and being reduced, as the anion (PF6-) will not enter the EDL. For the ether-based electrolyte, both the anion (TFSI-) and FEC can enter the EDL and be reduced. The competition of the two species within the EDL due to the surface charge and temperature leads to a unique temperature effect observed in prior experiments: the FEC additive is more effective in modulating SEI components at a low temperature (-40 °C) than at room temperature (20 °C) in the ether-based electrolyte. These collective quantitative agreements with experiments emphasize the importance of incorporating the effect of the EDL in multicomponent electrolyte reduction reactions in simulations/experiments to predict/control the formation of the SEI layer.

4.
Mol Carcinog ; 62(5): 665-675, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36752333

RESUMEN

This study aimed to investigate the relationship between anomalous DNA nucleotidylexotransferase (DNTT) activation and the mutagenesis of gene length mutations (LMs) in acute myeloid leukemia (AML), and the relevance of their prognosis in antithymocyte globulin (ATG)-based regimen allogeneic hematopoietic stem cell transplantation (allo-HSCT). A cohort of 578 AML cases was enrolled. Next-generation sequencing was performed to screen mutations of 86 leukemia driver genes. RNA-seq was used to analyze gene expression. Prognostic analysis was investigated in 239 AML cases who underwent ATG-based regimen allo-HSCT. We report a refined subtyping algorithm of LMs (type I-IV) based on sequence anatomy considering the TdT-aided mutagenesis mechanism. GC content adjacent to LM junctions, inserted nontemplate nucleotide bases, and DNTT expression analysis supported the DNTT activation and TdT-aided mutagenesis in type II/III LMs in the total AML cohort. Both single-variate and multivariate analyses showed a better overall survival of FLT3 type III compared to type I in a subset of ATG-based regimen allo-HSCT cases. The novel LM subtyping algorithm not only deciphers the etiology of the mutagenesis of LMs but also helps to fine-tune prognosis differentiation in AML. The possible prognostic versatility of this novel LM subtyping algorithm in terms of chemotherapy, targeted therapy, and allo-HSCT merits further investigation.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Humanos , ADN Nucleotidilexotransferasa/genética , Suero Antilinfocítico/genética , Suero Antilinfocítico/uso terapéutico , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/tratamiento farmacológico , Mutación , Estudios Retrospectivos
5.
Electrophoresis ; 42(7-8): 939-949, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-32705697

RESUMEN

We introduce herein an efficient microfluidic approach for continuous transport and localized collection of nanoparticles via hybrid electrokinetics, which delicately combines linear and nonlinear electrokinetics driven by a composite DC-biased AC voltage signal. The proposed technique utilizes a simple geometrical structure, in which one or a series of metal strips serving as floating electrode (FE) are attached to the substrate surface and arranged in parallel between a pair of coplanar driving electrodes (DE) in a straight microchannel. On application of a DC-biased AC electric field across the channel, nanoparticles can be transported continuously by DC bulk electroosmotic flow, and then trapped selectively onto the metal strips due to AC-field induced-charge electrokinetic (ICEK) phenomenon, which behaves as counter-rotating micro-vortices around the ideally polarizable surfaces of FE. Finite-element simulation is carried out by coupling the dual-frequency electric field, flow field and sample mass transfer in sequence, for guiding a practical design of the microfluidic nanoparticle concentrator. With the optimal device geometry, the actual performance of the technique is investigated with respect to DC bias, AC voltage amplitude, and field frequency by using both latex nanospheres (∼500 nm) and BSA molecules (∼10 nm). Our experimental observation indicates nanoparticles are always enriched into a narrow bright band on the surface of each FE, and a horizontal concentration gradient even emerges in the presence of multiple metal strips, which therefore permits localized analyte enrichment. The proposed trapping method is supposed to guide an elaborate design of flexible electrokinetic frameworks embedding FE for continuous-flow analyte manipulation in modern microfluidic systems.


Asunto(s)
Microfluídica , Nanopartículas , Electricidad , Electroósmosis
6.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 38(4): 351-354, 2021 Apr 10.
Artículo en Zh | MEDLINE | ID: mdl-33834463

RESUMEN

OBJECTIVE: To detect fusion gene with pathological significance in a patient with refractory and relapsed acute B cell lymphoblastic leukemia (B-ALL) and to explore its laboratory and clinical characteristics. METHODS: Transcriptome sequencing was used to detect potential fusion transcripts. Other laboratory results and clinical data of the patient were also analyzed. RESULTS: The patient was found to harbor TCF3 exon 17-ZNF384 exon 7 in-frame fusion transcript. The minimal residual disease (MRD) has remained positive after multiple chemotherapy protocols including CD19-, CD22- targeted chimeric antigen receptor T cells immunotherapy. The patient eventually achieved complete remission and sustained MRD negativity after allogeneic hemopoietic stem cell transplantation (allo-HSCT). CONCLUSION: Transcriptome sequencing can effectively detect potential fusion genes with clinical significance in leukemia. TCF3-ZNF384 positive B-ALL has unique laboratory and clinical characteristics, may not well respond to chemotherapy and immunotherapy, and is more likely to relapse. Timely allo-HSCT treatment may help such patients to achieve long-term disease-free survival. TCF3-ZNF384 positive B-ALL is not uncommon in pediatric patients but has not been effectively identified.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras , Linfocitos B , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Niño , Humanos , Laboratorios , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Transactivadores/genética , Transcriptoma
7.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 52(1): 50-56, 2021 Jan.
Artículo en Zh | MEDLINE | ID: mdl-33474889

RESUMEN

Historically, the Cambrian explosion was a major life evolution event caused by changes of natural environmental oxygen concentration. The use of oxygen was part of the basic survival instinct of higher life, which evolved a complex regulation system in response to variant levels of oxygen concentration. Hypoxia is one of the typical environmental characteristics in plateau areas. After long-term natural selection in hypoxic conditions, numerous species living in plateau areas have evolved unique mechanisms adapted to hypoxia. Recent studies have found that there are some similarities in adaptation to hypoxia between the animals in highland and different types of human solid tumor cells. Herein, we will summarize recent findings about the hypoxia adaptation evolution in high-altitude animals and the characteristics of hypoxic solid tumors, especially the reactive oxygen species responses in hypoxic solid tumors. We believe that deciphering the underlying molecular mechanisms involved in hypoxia adaptation in highland will facilitate the identification of new genes or biomarkers critical for research on hypoxic solid tumors in the future.


Asunto(s)
Mal de Altura , Altitud , Aclimatación , Animales , Humanos , Hipoxia , Oxígeno , Selección Genética
8.
BMC Genomics ; 21(1): 443, 2020 Jun 29.
Artículo en Inglés | MEDLINE | ID: mdl-32600250

RESUMEN

BACKGROUND: The gonad is the major factor affecting animal reproduction. The regulatory mechanism of the expression of protein-coding genes involved in reproduction still remains to be elucidated. Increasing evidence has shown that ncRNAs play key regulatory roles in gene expression in many life processes. The roles of microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) in reproduction have been investigated in some species. However, the regulatory patterns of miRNA and lncRNA in the sex biased expression of protein coding genes remains to be elucidated. In this study, we performed an integrated analysis of miRNA, messenger RNA (mRNA), and lncRNA expression profiles to explore their regulatory patterns in the female ovary and male testis of Pelodiscus sinensis. RESULTS: We identified 10,446 mature miRNAs, 20,414 mRNAs and 28,500 lncRNAs in the ovaries and testes, and 633 miRNAs, 11,319 mRNAs, and 10,495 lncRNAs showed differential expression. A total of 2814 target genes were identified for miRNAs. The predicted target genes of these differentially expressed (DE) miRNAs and lncRNAs included abundant genes related to reproductive regulation. Furthermore, we found that 189 DEmiRNAs and 5408 DElncRNAs showed sex-specific expression. Of these, 3 DEmiRNAs and 917 DElncRNAs were testis-specific, and 186 DEmiRNAs and 4491 DElncRNAs were ovary-specific. We further constructed complete endogenous lncRNA-miRNA-mRNA networks using bioinformatics, including 103 DEmiRNAs, 636 DEmRNAs, and 1622 DElncRNAs. The target genes for the differentially expressed miRNAs and lncRNAs included abundant genes involved in gonadal development, including Wt1, Creb3l2, Gata4, Wnt2, Nr5a1, Hsd17, Igf2r, H2afz, Lin52, Trim71, Zar1, and Jazf1. CONCLUSIONS: In animals, miRNA and lncRNA as master regulators regulate reproductive processes by controlling the expression of mRNAs. Considering their importance, the identified miRNAs, lncRNAs, and their targets in P. sinensis might be useful for studying the molecular processes involved in sexual reproduction and genome editing to produce higher quality aquaculture animals. A thorough understanding of ncRNA-based cellular regulatory networks will aid in the improvement of P. sinensis reproductive traits for aquaculture.


Asunto(s)
Perfilación de la Expresión Génica/veterinaria , Gónadas/química , MicroARNs/genética , ARN Largo no Codificante/genética , Tortugas/fisiología , Animales , Femenino , Regulación de la Expresión Génica , Ontología de Genes , Redes Reguladoras de Genes , Masculino , Reproducción , Análisis de Secuencia de ARN , Caracteres Sexuales , Tortugas/genética
9.
J Am Chem Soc ; 142(30): 13090-13101, 2020 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-32615759

RESUMEN

Localized surface plasmon resonances (LSPRs) have attracted much recent attention for their potential in promoting chemical reactions with light. However, the mechanism of LSPR-induced chemical reactions is still not clear, even for H2 dissociation on metal nanoparticles. In this work, we investigate the mechanism for photoinduced H2 dissociation using a simple H2@Au6 model. Our time-dependent density functional theory calculations indicate that the initial excitation is largely restricted to the metal cluster, involving intraband excitation that produces hot electrons (HEs). However, diabatization via overlapping orbitals reveals two types of nested electronic states, one involving excitations of the metallic electrons, namely, the HE states, and the other concerned with charge transfer (CT) to the adsorbate antibonding σ* orbital. Dissociation of H2 thus takes place by transitions from the former to the latter. Quantum dynamics simulations on the diabatic CT states suggest rapid dissociation of H2, while no such dissociation occurs on diabatic HE states. Our research provides a clear physical picture of photoinduced H2 dissociation on Au clusters, which has important implications in plasmonic facilitated photocatalysis.

10.
Anal Chem ; 92(3): 2468-2475, 2020 02 04.
Artículo en Inglés | MEDLINE | ID: mdl-31782306

RESUMEN

Effective characterization and imaging of endogenous RNA transcripts have important value in the diagnosis, treatment, and prognosis of diseases. Traditional qRT-PCR as a liquid-based RNA detection method might lead to false-negative results due to the admixture of too many nontarget cells. Also, many in situ RNA imaging methods were hindered by long turnaround time and insufficient signals. Here, we describe and evaluate a CRISPR/dCas9-MS2-based RNA fluorescence in situ hybridization assay (RCasFISH) for in situ amplified imaging and quantification of RNA transcripts in fixed cells as well as formalin-fixed, paraffin-embedded (FFPE) tissue sections at a single-molecular level in individual cells. Compared to single molecular FISH (smFISH), RCasFISH yields brighter dot signals and a better signal-to-noise ratio (SNR) with lower costs and less than 1.5 h of hybridization. In addition, by using human epidermal growth factor receptor 2 (HER2) as a model, we quantified individual HER2 mRNA molecules in clinical breast cancer FFPE tissue sections and demonstrated its potential to resolve FISH-equivocal cases. Therefore, RCasFISH may provide a new approach for gene expression studies in basic research and hold the potential for molecular diagnostic applications.


Asunto(s)
Sistemas CRISPR-Cas/genética , Hibridación Fluorescente in Situ , ARN Mensajero/genética , Humanos , Rayos Láser , Microscopía Confocal , Reacción en Cadena en Tiempo Real de la Polimerasa , Fijación del Tejido , Células Tumorales Cultivadas
11.
Electrophoresis ; 41(10-11): 778-792, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-31943244

RESUMEN

We study herein numerically the use of induced-charge electrokinetic phenomena to enable a flexible control of ion transport of dilute electrolyte in a straight ion concentration polarization system. The effect of three convection modes of induced-charge electrokinetic phenomena, including induced-charge electroosmosis, flow-field effect transistor, and alternating-current electroosmosis (ACEO), on convective arrestment of diffusive wave-front propagation is investigated by developing a cross-scale and fully coupled transient numerical simulation model, wherein multiple frequency electrochemical polarization and nonlinear diffuse charge dynamics in spatiotemporally varying solution conductivity are taken into account. We demonstrate by detailed comparative simulation studies that ACEO vortex flow field above a metal strip array arranged along the anodic chamber's bottom surface serves as the most efficient way for adjusting the salt density distribution at micrometer and even millimeter dimension, due to its high flexibility in controlling the stirring flow state with the introduction of two extra electrical parameters. The specific operating status is determined by whether the electrode array is floating in potential (induced-charge electroosmosis) or biased to ground (flow-field effect transistor) or forced to oscillate at another Fourier mode (ACEO). These results prove useful for on-chip electric current control with electroconvective stirring.


Asunto(s)
Electroósmosis/métodos , Iones/química , Microfluídica/métodos , Simulación por Computador , Conductividad Eléctrica , Electrólitos/química , Dinámicas no Lineales
12.
Electrophoresis ; 40(20): 2683-2698, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-30883820

RESUMEN

The phenomenon of electrothermal (ET) convection has recently captured great attention for transporting fluidic samples in microchannels embedding simple electrode structures. In the classical model of ET-induced flow, a conductivity gradient of buffer medium is supposed to arise from temperature-dependent electrophoretic mobility of ionic species under uniform salt concentrations, so it may not work well in the presence of evident concentration perturbation within the background electrolyte. To solve this problem, we develop herein a microscopic physical description of ET streaming by fully coupling a set of Poisson-Nernst-Planck-Navier-Stokes equations and temperature-dependent fluid physicochemical properties. A comparative study on a standard electrokinetic micropump exploiting asymmetric electrode arrays indicates that, our microscopic model always predicts a lower ET pump flow rate than the classical macroscopic model even with trivial temperature elevation in the liquid. Considering a continuity of total current density in liquids of inhomogeneous polarizability, a moderate degree of fluctuation in ion concentrations on top of the electrode array is enough to exert a significant influence on the induction of free ionic charges, rendering the enhanced numerical treatment much closer to realistic experimental measurement. Then, by placing a pair of thin-film resistive heaters on the bottom of an anodic channel interfacing a cation-exchange medium, we further provide a vivid demonstration of the enhanced model's feasibility in accurately resolving the combined Coulomb force due to the coexistence of an extended space charge layer and smeared interfacial polarizations in an externally-imposed temperature gradient, while this is impossible with conventional linear approximation. This leads to a reliable method to achieve a flexible regulation on spatial-temporal evolution of ion-depletion layer by electroconvective mixing. These results provide useful insights into ET-based flexible control of micro/nanoscale solid entities in modern micro-total-analytical systems.


Asunto(s)
Técnicas Electroquímicas/métodos , Técnicas Analíticas Microfluídicas/métodos , Microscopía/métodos , Nanotecnología/métodos , Simulación por Computador , Convección , Técnicas Electroquímicas/instrumentación , Diseño de Equipo , Iones/química , Técnicas Analíticas Microfluídicas/instrumentación , Microscopía/instrumentación , Nanotecnología/instrumentación , Cloruro de Sodio/química
13.
Electrophoresis ; 40(6): 979-992, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30256428

RESUMEN

Induced-charge electroosmosis (ICEO) has attracted tremendous popularity for driving fluid motion from the microfluidic community since the last decade, while less attention has been paid to ICEO-based nanoparticle manipulation. We propose herein a unique concept of hybrid electroosmotic kinetics (HEK) in terms of bi-phase ICEO (BICEO) actuated in a four-terminal spiral electrode array, for effective electrokinetic enrichment of fluorescent polystyrene nanoparticles on ideally polarizable metal strips. First, by alternating the applied AC voltage waves between consecutive discrete terminals, the flow stagnation lines where the sample nanoparticles aggregate can be switched in time between two different distribution modes. Second, we innovatively introduce the idea of AC field-effect flow control on BICEO; by altering the combination of gating voltage sequence, not only the number of circulative particle trapping lines is doubled, but the collecting locations can be flexibly reconfigured as well. Third, hydrodynamic streaming of DC-biased BICEO is tested in our device design, wherein the global linear electroosmosis dominates BICEO contributed from both AC and DC components, resulting in a reduction of particle enrichment area, while with a sharp increase in sample transport speed inside the bulk phase. The flow field associated with HEK is predicted using a linear asymptotic analysis under Debye-Huckel limit, with the simulation results in qualitative agreement with in-lab observations of nanoparticle trapping by exploiting a series of improved ICEO techniques. This work provides an affordable and field-deployable platform for real-time nanoparticle trapping in the context of dilute electrolyte.


Asunto(s)
Electroósmosis/instrumentación , Técnicas Analíticas Microfluídicas/instrumentación , Nanopartículas/química , Electricidad , Electroósmosis/métodos , Diseño de Equipo , Cinética , Microelectrodos
14.
Ann Hematol ; 98(10): 2347-2355, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31446458

RESUMEN

Molecular measurable residual disease (MRD) monitoring based on real-time quantitative reverse transcription PCR (RT-qPCR) plays an important role in acute promyelocytic leukemia (APL) management, but the performance status of clinical reports is unknown. This study focuses on the specific elements in molecular MRD monitoring report and their impact on clinical decision-making. The participating laboratories were asked to submit real and formal clinical reports for mock samples panel with APL clinical case. The MRD-specific elements were analyzed and summarized. The significance of longitudinal MRD monitoring curve and the missing MRD-specific elements for clinical decision-making were assessed. MRD-specific elements were significantly missing in clinical reports. The element "testing results" existed great inconsistencies in the written form of testing items and data. The longitudinal MRD monitoring curve of false-negative or false-positive MRD result was obviously different from all-correct. It not only identified MRD time point of tissue sampling relative to treatment and ensured the reliability of the negative MRD results, but also gave MRD diagnosis, clinical interpretation, and further recommendation. Clinician-friendly reports with MRD-specific elements can better serve clinical practice. The correctly intuitive results and clinically important MRD-specific elements can provide a good description of the reliability and clinical significance of MRD results.


Asunto(s)
Registros Electrónicos de Salud , Leucemia Promielocítica Aguda , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Humanos , Leucemia Promielocítica Aguda/sangre , Leucemia Promielocítica Aguda/genética , Monitoreo Fisiológico/métodos , Neoplasia Residual
15.
J Clin Lab Anal ; 33(6): e22894, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31131502

RESUMEN

BACKGROUND: The confirmation of clinical diagnosis, molecular remission, and sequential minimal residual disease monitoring required PML-RARα detection in acute promyelocytic leukemia (APL). The current status of PML-RARα detection in various laboratories remains unknown. METHODS: In 2018, external quality assessment (EQA) for PML-RARα detection was carried out in China. Three EQA sample panels for PML-RARα isoform L/S/V were prepared by different mock leukocyte samples. The performances of PML-RARα detection, including admission screening, and qualitative and quantitative detection by real-time quantitative reverse transcription PCR (RT-qPCR), were assessed based on APL simulated clinical case. RESULTS: The mock leukocyte samples met the requirements of a clinically qualified sample for PML-RARα EQA panel. Among the laboratories, 13/50 (26.0%) were "competent," 21/50 (42%) classified as "acceptable," and 16/50 (32.0%) classified as "improvable." One (1/50, 2.0%) laboratory reported one screening mistake. Twenty-six (26/50, 52.0%) laboratories reported 29 false-positive and 19 false-negative results. Twenty-three (23/50, 46.0%) laboratories reported 42 quantitative incorrect results. CONCLUSION: Significant differences were not found in PML-RARα detection performance among laboratories that used different extraction methods. The performances of qualitative and quantitative RT-qPCR detection were worse accurate for PML-RARα isoform V. Quantitative variation was higher for low-level samples. Further continuous external assessment and education are needed in the management of PML-RARα detection.


Asunto(s)
Técnicas de Laboratorio Clínico/normas , Leucemia Promielocítica Aguda/genética , Proteínas de Fusión Oncogénica/genética , Reacción en Cadena en Tiempo Real de la Polimerasa/normas , China , Humanos , Leucocitos/fisiología , Proteínas de Fusión Oncogénica/sangre , Isoformas de Proteínas/genética , Control de Calidad , ARN Ribosómico 23S
16.
J Clin Lab Anal ; 32(9): e22612, 2018 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-29959790

RESUMEN

BACKGROUND: Standards play an important role in detection of the BCR-ABL1 fusion gene (FG) transcript. However, the standards widely used in laboratories are mainly based on plasmids or cDNA, which cannot accurately reflect the process of RNA extraction and cDNA synthesis. Therefore, we aimed to develop armored RNA-based standards for p210 and p190 BCR-ABL1FG transcripts' quantification. METHODS: Using overlapping polymerase chain reaction (PCR) technology, we first linked a segment of the p210 or p190 BCR-ABL1FG transcript with four control genes (CGs; ABL1, BCR, GUSB, and B2M) to form p210FG-CG and p190FG-CG. Subsequently, using armored RNA technology, we prepared p210FG-CG- and p190FG-CG-armored RNAs and the p210FG-CG and p190FG-CG standards, the values of which were assigned by digital PCR (dPCR). RESULTS: The p210FG-CG and p190FG-CG standards were stable and homogeneous, and were significantly linear with r2  > 0.98. A field trial including 52 laboratories across China showed that the coefficient of variation (CV%) of BCR-ABL1 values among samples was in the range of 58.6%-129.6% for p210 samples and 73.2%-194.0% for p190 samples when using local standards. By contrast, when using the p210FG-CG and p190FG-CG standards, the CV% of BCR-ABL1 values was decreased to 35.6%-124.9% and 36.6%-170.6% for p210 and p190 samples, respectively. In addition, 33.3% (3/9) of the p210 and p190 samples had CV% values <50.0%, whereas 44.4% (4/9) and 77.8% (7/9) of the samples had lower CV% values when using the p210FG-CG and p190FG-CG standards. CONCLUSION: The overall variability of detection of BCR-ABL1 transcripts decreased significantly when using the p210FG-CG or p190FG-CG standards, especially the p190FG-CG standard.


Asunto(s)
Proteínas de Fusión bcr-abl/análisis , Proteínas de Fusión bcr-abl/genética , Reacción en Cadena de la Polimerasa/métodos , ARN Mensajero/análisis , Humanos , Distribución Normal , ARN/análisis , Valores de Referencia
17.
J Clin Lab Anal ; 32(5): e22391, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-29380513

RESUMEN

BACKGROUND: KRAS mutations are the key indicator for EGFR monoclonal antibody-targeted therapy and acquired drug resistance, and their accurate detection is critical to the clinical decision-making of colorectal cancer. However, no proper quality control material is available for the current detection methods, particularly next-generation sequencing (NGS). The ideal quality control material for NGS needs to provide both the tumor mutation gene and the matched background genomic DNA, which is uncataloged in public databases, to accurately distinguish germline polymorphisms and somatic mutations. METHODS: We developed a novel KRAS G12V mutant cell line using the clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9) technique to make up for the deficiencies in existing quality control material and further validated the feasibility of the cell line as quality control material by amplification refractory mutation system (ARMS), Sanger sequencing, digital PCR (dPCR), and NGS. RESULTS: We verified that the edited cell line specifically had the G12V mutation, and the validation results presented a high consistency among the four methods of detection. The three cell lines screened contained the G12V mutation and the mutation allele fractions of G12V-1, G12V-2, and G12V-3 were 52.01%, 82.06%, and 17.29%, respectively. CONCLUSION: The novel KRAS G12V cell line generated using the CRISPR/Cas9 gene editing system is suitable as a quality control material for all current detection methods and provides a new direction in the development of quality control material.


Asunto(s)
Sistemas CRISPR-Cas/genética , Glicina/genética , Mutación/genética , Proteínas Proto-Oncogénicas p21(ras)/genética , Valina/genética , Línea Celular , Análisis Mutacional de ADN , Células HEK293 , Humanos , Transfección
18.
Sensors (Basel) ; 18(2)2018 Feb 19.
Artículo en Inglés | MEDLINE | ID: mdl-29463046

RESUMEN

Methods dealing with the problem of Joint Tracking and Classification (JTC) are abundant, among which Simultaneous Tracking and Classification (STC) provides a modularized scheme solving tracking and classification subproblems simultaneously. However, there is no explicit hard decision on the class label but only soft decision (class probability) is provided. This does not fit many practical cases, in which a hard decision is urgently needed. To solve this problem, this paper proposes a Hard decision-based STC (HSTC) method. HSTC takes all the decision error rate, timeliness, and estimation error into account. Specifically, for decision, the sequential probability ratio test is adopted due to its nice properties and also the adaptability to our situation. For estimation, by utilizing the two-way information exchange between the tracker and the classifier, we propose flexible three tracking schemes related to decision. The HSTC tracking result is divided into three parts according to the time of making the hard decision. In general, the proposed HSTC method takes advantage of both SPRT and STC. Finally, two illustrative JTC examples with hard decision verify the effectiveness of the the proposed HSTC method. They show that HSTC can meet the demand of the problem, and also has the performance superiority in both decision and estimation.

19.
Sensors (Basel) ; 18(5)2018 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-29758000

RESUMEN

In spatial spectrum estimation, difference co-array can provide extra degrees-of-freedom (DOFs) for promoting parameter identifiability and parameter estimation accuracy. For the sake of acquiring as more DOFs as possible with a given number of physical sensors, we herein design a novel sensor array geometry named cascade array. This structure is generated by systematically connecting a uniform linear array (ULA) and a non-uniform linear array, and can provide more DOFs than some exist array structures but less than the upper-bound indicated by minimum redundant array (MRA). We further apply this cascade array into multiple input multiple output (MIMO) array systems, and propose a novel joint direction of departure (DOD) and direction of arrival (DOA) estimation algorithm, which is based on a reduced-dimensional weighted subspace fitting technique. The algorithm is angle auto-paired and computationally efficient. Theoretical analysis and numerical simulations prove the advantages and effectiveness of the proposed array structure and the related algorithm.

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