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1.
Nature ; 548(7669): 561-566, 2017 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-28846999

RESUMO

Magnetic skyrmions are topologically stable, vortex-like objects surrounded by chiral boundaries that separate a region of reversed magnetization from the surrounding magnetized material. They are closely related to nanoscopic chiral magnetic domain walls, which could be used as memory and logic elements for conventional and neuromorphic computing applications that go beyond Moore's law. Of particular interest is 'racetrack memory', which is composed of vertical magnetic nanowires, each accommodating of the order of 100 domain walls, and that shows promise as a solid state, non-volatile memory with exceptional capacity and performance. Its performance is derived from the very high speeds (up to one kilometre per second) at which chiral domain walls can be moved with nanosecond current pulses in synthetic antiferromagnet racetracks. Because skyrmions are essentially composed of a pair of chiral domain walls closed in on themselves, but are, in principle, more stable to perturbations than the component domain walls themselves, they are attractive for use in spintronic applications, notably racetrack memory. Stabilization of skyrmions has generally been achieved in systems with broken inversion symmetry, in which the asymmetric Dzyaloshinskii-Moriya interaction modifies the uniform magnetic state to a swirling state. Depending on the crystal symmetry, two distinct types of skyrmions have been observed experimentally, namely, Bloch and Néel skyrmions. Here we present the experimental manifestation of another type of skyrmion-the magnetic antiskyrmion-in acentric tetragonal Heusler compounds with D2d crystal symmetry. Antiskyrmions are characterized by boundary walls that have alternating Bloch and Néel type as one traces around the boundary. A spiral magnetic ground-state, which propagates in the tetragonal basal plane, is transformed into an antiskyrmion lattice state under magnetic fields applied along the tetragonal axis over a wide range of temperatures. Direct imaging by Lorentz transmission electron microscopy shows field-stabilized antiskyrmion lattices and isolated antiskyrmions from 100 kelvin to well beyond room temperature, and zero-field metastable antiskyrmions at low temperatures. These results enlarge the family of magnetic skyrmions and pave the way to the engineering of complex bespoke designed skyrmionic structures.

2.
Scand J Clin Lab Invest ; 81(1): 8-11, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33345642

RESUMO

After intravenous supplementation of an unintentionally high dose of the antioxidant alpha-lipoic acid (ALA), a 53-year-old female complained of myalgia, chills and nausea, and showed signs of haemorrhagic diathesis. The laboratory findings were excessive hyperferritinemia, leukoerythroblastosis, severe thrombocytopenia, elevated liver enzymes and impaired coagulation. The toxicological tests resulted in an ALA serum concentration of 10 280 µg/L. The peripheral blood film of the patient showed some neutrophil dysplasia with unusual small dark-blue stained round cytoplasmic inclusions resembling 'Howell-Jolly-body-like' (HJBL) cytoplasmic inclusions, aptly named due to the morphologic similarity to their erythrocytic counterparts. Such HJBL inclusions are occasionally associated with acquired immunodeficiency, or immunosuppressive or cytostatic treatment. An association with ALA intoxication has not been described before. There are only a few reports on unintentional, harmful and lethal intoxications with ALA. The underlying molecular background of its toxicity on liver function or haematopoiesis is not yet known in detail, but ALA seems to interact with enzyme functions, e.g. with mitochondrial enzyme-complexes, possibly due to its pro-oxidant potential at high doses.


Assuntos
Corpos de Inclusão/patologia , Neutrófilos/patologia , Ácido Tióctico/toxicidade , Feminino , Hospitalização , Humanos , Corpos de Inclusão/efeitos dos fármacos , Pessoa de Meia-Idade , Neutrófilos/efeitos dos fármacos
3.
Nano Lett ; 20(1): 59-65, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31809059

RESUMO

Recently, magnetic antiskyrmions were discovered in Mn1.4Pt0.9Pd0.1Sn, an inverse tetragonal Heusler compound that is nominally a ferrimagnet, but which can only be formed with substantial Mn vacancies. The vacancies reduce considerably the compensation of the moments between the two expected antiferromagnetically coupled Mn sub-lattices so that the overall magnetization is very high and the compound is almost a "ferromagnet". Here, we report the observation of antiskyrmions in a second inverse tetragonal Heusler compound, Mn2Rh0.95Ir0.05Sn, which can be formed stoichiometrically without any Mn vacancies and which thus exhibits a much smaller magnetization. Individual and lattices of antiskyrmions can be stabilized over a wide range of temperature from near room temperature to 100 K, the base temperature of the Lorentz transmission electron microscope used to image them. In low magnetic fields helical spin textures are found which evolve into antiskyrmion structures in the presence of small magnetic fields. A weaker Dzyaloshinskii-Moriya interaction (DMI), that stabilizes the antiskyrmions, is expected for the 4d element Rh as compared to the 5d element Pt, so that the observation of antiskyrmions in Mn2Rh0.95Ir0.05Sn establishes the intrinsic stability of antiskyrmions in these Heusler compounds. Moreover, the finding of antiskyrmions with substantially lower magnetization promises, via chemical tuning, even zero moment antiskyrmions with important technological import.

4.
Int J Mol Sci ; 22(10)2021 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-34065900

RESUMO

Within the last decades cancer treatment improved by the availability of more specifically acting drugs that address molecular target structures in cancer cells. However, those target-sensitive drugs suffer from ongoing resistances resulting from mutations and moreover they are affected by the cancer phenomenon of multidrug resistance. A multidrug resistant cancer can hardly be treated with the common drugs, so that there have been long efforts to develop drugs to combat that resistance. Transmembrane efflux pumps are the main cause of the multidrug resistance in cancer. Early inhibitors disappointed in cancer treatment without a proof of expression of a respective efflux pump. Recent studies in efflux pump expressing cancer show convincing effects of those inhibitors. Based on the molecular symmetry of the efflux pump multidrug resistant protein (MRP) 4 we synthesized symmetric inhibitors with varied substitution patterns. They were evaluated in a MRP4-overexpressing cancer cell line model to prove structure-dependent effects on the inhibition of the efflux pump activity in an uptake assay of a fluorescent MRP4 substrate. The most active compound was tested to resentisize the MRP4-overexpressing cell line towards a clinically relevant anticancer drug as proof-of-principle to encourage for further preclinical studies.


Assuntos
Antineoplásicos/farmacologia , Di-Hidropiridinas/farmacologia , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Neoplasias Pancreáticas/genética , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Di-Hidropiridinas/síntese química , Di-Hidropiridinas/química , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células HEK293 , Humanos , Proteínas Associadas à Resistência a Múltiplos Medicamentos/antagonistas & inibidores , Proteínas Associadas à Resistência a Múltiplos Medicamentos/química , Neoplasias Pancreáticas/tratamento farmacológico , Relação Estrutura-Atividade , Regulação para Cima/efeitos dos fármacos
5.
Plant J ; 99(6): 1172-1191, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31108005

RESUMO

Broadening the genetic base of crops is crucial for developing varieties to respond to global agricultural challenges such as climate change. Here, we analysed a diverse panel of 371 domesticated lines of the model crop barley to explore the genetics of crop adaptation. We first collected exome sequence data and phenotypes of key life history traits from contrasting multi-environment common garden trials. Then we applied refined statistical methods, including some based on exomic haplotype states, for genotype-by-environment (G×E) modelling. Sub-populations defined from exomic profiles were coincident with barley's biology, geography and history, and explained a high proportion of trial phenotypic variance. Clear G×E interactions indicated adaptation profiles that varied for landraces and cultivars. Exploration of circadian clock-related genes, associated with the environmentally adaptive days to heading trait (crucial for the crop's spread from the Fertile Crescent), illustrated complexities in G×E effect directions, and the importance of latitudinally based genic context in the expression of large-effect alleles. Our analysis supports a gene-level scientific understanding of crop adaption and leads to practical opportunities for crop improvement, allowing the prioritisation of genomic regions and particular sets of lines for breeding efforts seeking to cope with climate change and other stresses.


Assuntos
Aclimatação/genética , Produtos Agrícolas/genética , Exoma , Hordeum/genética , Relógios Circadianos/genética , Variação Genética , Estudo de Associação Genômica Ampla , Genótipo , Geografia , Haplótipos , Desequilíbrio de Ligação , Fenótipo , Melhoramento Vegetal , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas , Sequenciamento do Exoma
6.
Theor Appl Genet ; 133(4): 1243-1264, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31965232

RESUMO

KEY MESSAGE: Diagnostic markers for Rrs1Rh4 have been identified by testing for associations between SNPs within the Rrs1 interval in 150 barley genotypes and their resistance to Rhynchosporium commune isolates recognised by lines containing Rrs1. Rhynchosporium or barley scald, caused by the destructive fungal pathogen Rhynchosporium commune, is one of the most economically important diseases of barley in the world. Barley landraces from Syria and Jordan demonstrated high resistance to rhynchosporium in the field. Genotyping of a wide range of barley cultivars and landraces, including known sources of different Rrs1 genes/alleles, across the Rrs1 interval, followed by association analysis of this genotypic data with resistance phenotypes to R. commune isolates recognised by Rrs1, allowed the identification of diagnostic markers for Rrs1Rh4. These markers are specific to Rrs1Rh4 and do not detect other Rrs1 genes/alleles. The Rrs1Rh4 diagnostic markers represent a resource that can be exploited by breeders for the sustainable deployment of varietal resistance in new cultivars. Thirteen out of the 55 most resistant Syrian and Jordanian landraces were shown to contain markers specific to Rrs1Rh4. One of these lines came from Jordan, with the remaining 12 lines from different locations in Syria. One of the Syrian landraces containing Rrs1Rh4 was also shown to have Rrs2. The remaining landraces that performed well against rhynchosporium in the field are likely to contain other resistance genes and represent an important novel resource yet to be exploited by European breeders.


Assuntos
Ascomicetos/fisiologia , Resistência à Doença/genética , Loci Gênicos , Hordeum/genética , Hordeum/microbiologia , Doenças das Plantas/genética , Doenças das Plantas/microbiologia , Alelos , Segregação de Cromossomos/genética , Ecótipo , Exoma/genética , Genes de Plantas , Marcadores Genéticos , Genótipo , Geografia , Proteínas de Fluorescência Verde/metabolismo , Jordânia , Modelos Genéticos , Fenótipo , Polimorfismo de Nucleotídeo Único/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reprodutibilidade dos Testes , Síria
7.
Platelets ; 31(5): 680-684, 2020 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-31509045

RESUMO

MgSO4 is effective in preventing spontaneous in vitro platelet agglutination in anticoagulant-induced pseudothrombocytopenia (PTCP). In order to learn more about its potential as an in vitro anticoagulant, platelets from MgSO4-anticoagulated blood were stimulated by several differentially-acting agonists (ADP, ARA, TRAP, epinephrine, collagen and ristocetin). Platelet aggregation in blood samples from 11 and 17 volunteers was measured by light-transmission aggregometry (LTA) according to Born and impedance aggregometry (MultiplateTM), respectively. Agonist-induced platelet aggregation was markedly lower in MgSO4-anticoagulated samples when compared with citrate-anticoagulated samples (decrease of 95.75% (ristocetin), 69.02% (collagen) and 75.73% (epinephrine)) or hirudin-anticoagulated samples (decrease of 85.99% (ADP), 80.98% (ARA), 77.24% (ristocetin), 54.37% (collagen) and 50.14% (TRAP)). The anti-aggregatory effect of MgSO4 is dose-dependent and readily detectable at a concentration of 7.5 mmol/l. Analysis of the agonist signaling pathways suggest that MgSO4 interferes with the final step of platelet aggregation, namely the intracellular mobilization of Ca2+.


Assuntos
Analgésicos/uso terapêutico , Anticoagulantes/uso terapêutico , Sulfato de Magnésio/uso terapêutico , Agregação Plaquetária/efeitos dos fármacos , Trombocitopenia/tratamento farmacológico , Adulto , Idoso , Analgésicos/farmacologia , Anticoagulantes/farmacologia , Feminino , Voluntários Saudáveis , Humanos , Sulfato de Magnésio/farmacologia , Masculino , Pessoa de Meia-Idade , Adulto Jovem
8.
J Struct Biol ; 198(3): 186-195, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28323140

RESUMO

The skeletal system of Demospongiae consists of siliceous spicules, which are composed of an axial channel containing an organic axial filament (AF) surrounded by a compact layer of hydrated amorphous silica. Here we report the ultrastructural investigations of the AF of siliceous spicules from two Demospongiae: Suberites domuncula and Tethya aurantium. Electron microscopy, electron diffraction and elemental mapping analyses on both longitudinal and transversal cross-sections yield that spicules's AF consist of a three-dimensional crystal lattice of six-fold symmetry. Its structure, which is the result of a biological growth process, is a crystalline assembly characterized by a lattice of organic cages (periodicity in the range of 6nm) filled with enzymatically-produced silica. In general, the six-fold lattice symmetry is reflected by the morphology of the AF, which is characterized by six-fold facets. This seems to be the result of a lattice energy minimization process similar to the situation found during the growth of inorganic crystals. Our structural exploitation of three-dimensional organic lattices generated by biological systems is expected to contribute for explaining the relation between axial filament's ultrastructure and spicule's ultimate morphology.


Assuntos
Poríferos/anatomia & histologia , Dióxido de Silício/química , Animais , Cristalização , Análise de Elementos Finitos , Microscopia Eletrônica , Microscopia Eletrônica de Transmissão , Morfogênese , Compostos Orgânicos/química , Poríferos/química , Poríferos/crescimento & desenvolvimento , Poríferos/ultraestrutura , Suberites/ultraestrutura
9.
Eur J Nucl Med Mol Imaging ; 44(6): 1025-1032, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28197685

RESUMO

PURPOSE: The role of dopamine D1-type receptor (D1R)-expressing neurons in the regulation of motivated behavior and reward prediction has not yet been fully established. As a prerequisite for future research assessing D1-mediated neuronal network regulation using simultaneous PET/MRI and D1R-selective [11C]SCH23390, this study investigated the stability of central D1R measurements between two independent PET/MRI sessions under baseline conditions. METHODS: Thirteen healthy volunteers (7 female, age 33 ± 13 yrs) underwent 90-min emission scans, each after 90-s bolus injection of 486 ± 16 MBq [11C]SCH23390, on two separate days within 2-4 weeks using a PET/MRI system. Parametric images of D1R distribution volume ratio (DVR) and binding potential (BPND) were generated by a multi-linear reference tissue model with two parameters and the cerebellar cortex as receptor-free reference region. Volume-of-interest (VOI) analysis was performed with manual VOIs drawn on consecutive transverse MRI slices for brain regions with high and low D1R density. RESULTS: The DVR varied from 2.5 ± 0.3 to 2.9 ± 0.5 in regions with high D1R density (e.g. the head of the caudate) and from 1.2 ± 0.1 to 1.6 ± 0.2 in regions with low D1R density (e.g. the prefrontal cortex). The absolute variability of the DVR ranged from 2.4% ± 1.3% to 5.1% ± 5.3%, while Bland-Altman analyses revealed very low differences in mean DVR (e.g. 0.013 ± 0.17 for the nucleus accumbens). Intraclass correlation (one-way, random) indicated very high agreement (0.93 in average) for both DVR and BPND values. Accordingly, the absolute variability of BPND ranged from 7.0% ± 4.7% to 12.5% ± 10.6%; however, there were regions with very low D1R content, such as the occipital cortex, with higher mean variability. CONCLUSION: The test-retest reliability of D1R measurements in this study was very high. This was the case not only for D1R-rich brain areas, but also for regions with low D1R density. These results will provide a solid base for future joint PET/MRI data analyses in stimulation-dependent mapping of D1R-containing neurons and their effects on projections in neuronal circuits that determine behavior.


Assuntos
Imageamento por Ressonância Magnética , Imagem Multimodal , Tomografia por Emissão de Pósitrons , Receptores de Dopamina D1/metabolismo , Adulto , Benzazepinas , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Radioisótopos de Carbono , Feminino , Voluntários Saudáveis , Humanos , Masculino , Reprodutibilidade dos Testes
10.
Eur J Nucl Med Mol Imaging ; 44(7): 1119-1128, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28321471

RESUMO

PURPOSE: Amyloid-beta (Aß) peptides are involved in the inflammatory pathology of atherosclerosis. 18F-Florbetaben is a PET tracer for clinical imaging of cerebral Aß plaques in Alzheimer's disease (AD). We sought to determine whether specific uptake of 18F-florbetaben in the carotid arteries can be identified using a fully integrated hybrid PET/MRI system and whether this uptake is associated with clinical cardiovascular disease (CVD) risk factors. METHODS: Carotid 18F-florbetaben uptake was quantified as the mean of the maximum target-to-background ratio (meanTBRmax) in 40 cognitively impaired subjects (age 68.2 ± 9.5 years) undergoing 18F-florbetaben PET/MRI to diagnose AD. Associations between carotid 18F-florbetaben uptake and several CVD risk factors were assessed by univariate analysis followed by a multivariate linear regression analysis. Furthermore, carotid 18F-florbetaben uptake was compared between patients with and without a positive cerebral Aß PET scan. RESULTS: 18F-Florbetaben uptake was clearly visualized in the carotid arteries. Values of meanTBRmax corrected for the blood pool activity of the tracer showed specific 18F-florbetaben uptake in the carotid wall. Male gender was associated with carotid 18F-florbetaben uptake in the univariate analysis, and was found to be an independent predictor of 18F-florbetaben uptake in the multivariate regression analysis (standardized regression coefficient ß = 0.407, p = 0.009). Carotid 18F-florbetaben meanTBRmax in patients with a positive cerebral Aß scan did not differ from that in patients without cerebral Aß deposits. CONCLUSION: Specific 18F-florbetaben uptake in human carotid arteries was detected. Male gender was identified as an independent clinical risk factor. Therefore, 18F-florbetaben PET/MRI might provide new insights into the pathophysiological process in atherosclerosis.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Compostos de Anilina , Artérias Carótidas/diagnóstico por imagem , Artérias Carótidas/metabolismo , Imageamento por Ressonância Magnética , Imagem Multimodal , Tomografia por Emissão de Pósitrons , Estilbenos , Idoso , Aterosclerose/diagnóstico por imagem , Aterosclerose/metabolismo , Estudos Transversais , Estudos de Viabilidade , Feminino , Humanos , Masculino , Fatores de Risco
11.
Anal Bioanal Chem ; 409(3): 807-819, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27830315

RESUMO

The coil-to-globule transition of poly(N-isopropylacrylamide) (PNIPAM) microgel particles suspended in water has been investigated in situ as a function of heating and cooling rate with four optical process analytical technologies (PAT), sensitive to structural changes of the polymer. Photon Density Wave (PDW) spectroscopy, Focused Beam Reflectance Measurements (FBRM), turbidity measurements, and Particle Vision Microscope (PVM) measurements are found to be powerful tools for the monitoring of the temperature-dependent transition of such thermo-responsive polymers. These in-line technologies allow for monitoring of either the reduced scattering coefficient and the absorption coefficient, the chord length distribution, the reflected intensities, or the relative backscatter index via in-process imaging, respectively. Varying heating and cooling rates result in rate-dependent lower critical solution temperatures (LCST), with different impact of cooling and heating. Particularly, the data obtained by PDW spectroscopy can be used to estimate the thermodynamic transition temperature of PNIPAM for infinitesimal heating or cooling rates. In addition, an inverse hysteresis and a reversible building of micrometer-sized agglomerates are observed for the PNIPAM transition process.

12.
BMC Genomics ; 17: 500, 2016 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-27423334

RESUMO

BACKGROUND: The current approach to reducing the tendency for wheat grown under high fertilizer conditions to collapse (lodge) under the weight of its grain is based on reducing stem height via the introduction of Rht genes. However, these reduce the yield of straw (itself an important commodity) and introduce other undesirable characteristics. Identification of alternative height-control loci is therefore of key interest. In addition, the improvement of stem mechanical strength provides a further way through which lodging can be reduced. RESULTS: To investigate the prospects for genetic alternatives to Rht, we assessed variation for plant height and stem strength properties in a training genetic diversity panel of 100 wheat accessions fixed for Rht. Using mRNAseq data derived from RNA purified from leaves, functional genotypes were developed for the panel comprising 42,066 Single Nucleotide Polymorphism (SNP) markers and 94,060 Gene Expression Markers (GEMs). In the first application in wheat of the recently-developed method of Associative Transcriptomics, we identified associations between trait variation and both SNPs and GEMs. Analysis of marker-trait associations revealed candidates for the causative genes underlying the trait variation, implicating xylan acetylation and the COP9 signalosome as contributing to stem strength and auxin in the control of the observed variation for plant height. Predictive capabilities of key markers for stem strength were validated using a test genetic diversity panel of 30 further wheat accessions. CONCLUSIONS: This work illustrates the power of Associative Transcriptomics for the exploration of complex traits of high agronomic importance in wheat. The careful selection of genotypes included in the analysis, allowed for high resolution mapping of novel trait-controlling loci in this staple crop. The use of Gene Expression markers coupled with the more traditional sequence-based markers, provides the power required to understand the biological context of the marker-trait associations observed. This not only adds to the wealth of knowledge that we strive to accumulate regarding gene function and plant adaptation, but also provides breeders with the information required to make more informed decisions regarding the potential consequences of incorporating the use of particular markers into future breeding programmes.


Assuntos
Perfilação da Expressão Gênica , Estudos de Associação Genética , Variação Genética , Caules de Planta/genética , Transcriptoma , Triticum/genética , Marcadores Genéticos , Genótipo , Sequenciamento de Nucleotídeos em Larga Escala , Fenótipo , Polimorfismo de Nucleotídeo Único , Reprodutibilidade dos Testes
13.
J Exp Bot ; 67(14): 4169-78, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27217549

RESUMO

The precocious germination of cereal grains before harvest, also known as pre-harvest sprouting, is an important source of yield and quality loss in cereal production. Pre-harvest sprouting is a complex grain defect and is becoming an increasing challenge due to changing climate patterns. Resistance to sprouting is multi-genic, although a significant proportion of the sprouting variation in modern wheat cultivars is controlled by a few major quantitative trait loci, including Phs-A1 in chromosome arm 4AL. Despite its importance, little is known about the physiological basis and the gene(s) underlying this important locus. In this study, we characterized Phs-A1 and show that it confers resistance to sprouting damage by affecting the rate of dormancy loss during dry seed after-ripening. We show Phs-A1 to be effective even when seeds develop at low temperature (13 °C). Comparative analysis of syntenic Phs-A1 intervals in wheat and Brachypodium uncovered ten orthologous genes, including the Plasma Membrane 19 genes (PM19-A1 and PM19-A2) previously proposed as the main candidates for this locus. However, high-resolution fine-mapping in two bi-parental UK mapping populations delimited Phs-A1 to an interval 0.3 cM distal to the PM19 genes. This study suggests the possibility that more than one causal gene underlies this major pre-harvest sprouting locus. The information and resources reported in this study will help test this hypothesis across a wider set of germplasm and will be of importance for breeding more sprouting resilient wheat varieties.


Assuntos
Germinação/fisiologia , Dormência de Plantas/fisiologia , Locos de Características Quantitativas/genética , Triticum/crescimento & desenvolvimento , Mapeamento Cromossômico , Cromossomos de Plantas/genética , Cromossomos de Plantas/fisiologia , Genes de Plantas/genética , Genes de Plantas/fisiologia , Técnicas de Genotipagem , Germinação/genética , Dormência de Plantas/genética , Polimorfismo de Nucleotídeo Único/genética , Locos de Características Quantitativas/fisiologia , Triticum/genética
14.
Eur J Nucl Med Mol Imaging ; 43(12): 2236-2243, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27435367

RESUMO

PURPOSE: Established Alzheimer's disease (AD) biomarker concepts classify into amyloid pathology and neuronal injury biomarkers, while recent alternative concepts classify into diagnostic and progression AD biomarkers. However, combined amyloid positron emission tomography/magnetic resonance imaging (PET/MRI) offers the chance to obtain both biomarker category read-outs within one imaging session, with increased patient as well as referrer convenience. The aim of this pilot study was to investigate this matter for the first time. METHODS: 100 subjects (age 70 ± 10 yrs, 46 female), n = 51 with clinically defined mild cognitive impairment (MCI), n = 44 with possible/probable AD dementia, and n = 5 with frontotemporal lobe degeneration, underwent simultaneous [18F]florbetaben or [11C]PIB PET/MRI (3 Tesla Siemens mMR). Brain amyloid load, mesial temporal lobe atrophy (MTLA) by means of the Scheltens scale, and other morphological brain pathologies were scored by respective experts. The patients/caregivers as well as the referrers were asked to assess on a five-point scale the convenience related to the one-stop-shop PET and MRI approach. RESULTS: In three subjects, MRI revealed temporal lobe abnormalities other than MTLA. According to the National Institute on Aging-Alzheimer's Association classification, the combined amyloid-beta PET/MRI evaluation resulted in 31 %, 45 %, and 24 % of the MCI subjects being categorized as "MCI-unlikely due to AD", "MCI due to AD-intermediate likelihood", and "MCI due to AD-high likelihood", respectively. 50 % of the probable AD dementia patients were categorized as "High level of evidence of AD pathophysiological process", and 56 % of the possible AD dementia patients as "Possible AD dementia - with evidence of AD pathophysiological process". With regard to the International Working Group 2 classification, 36 subjects had both positive diagnostic and progression biomarkers. The patient/caregiver survey revealed a gain of convenience in 88 % of responders as compared to a theoretically separate PET and MR imaging. In the referrer survey, an influence of the combined amyloid-beta PET/MRI on the final diagnosis was reported by 82 % of responders, with a referrer acceptance score of 3.7 ± 1.0 on a 5-point scale. CONCLUSION: Simultaneous amyloid PET/MRI is feasible and provides imaging biomarkers of all categories which are able to supplement the clinical diagnosis of MCI due to AD and that of AD dementia. Further, patient and referrer convenience is improved by this one-stop-shop imaging approach.


Assuntos
Doença de Alzheimer/diagnóstico por imagem , Amiloide/metabolismo , Disfunção Cognitiva/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Aceitação pelo Paciente de Cuidados de Saúde , Tomografia por Emissão de Pósitrons/métodos , Idoso , Doença de Alzheimer/metabolismo , Atitude do Pessoal de Saúde , Biomarcadores/metabolismo , Disfunção Cognitiva/metabolismo , Estudos de Viabilidade , Feminino , Humanos , Aumento da Imagem/métodos , Masculino , Imagem Molecular/métodos , Imagem Multimodal/métodos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
15.
Nanotechnology ; 27(7): 075705, 2016 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-26775681

RESUMO

A set of Si1-x Sn x /Si(001) quantum wells (QWs) is grown by applying molecular beam epitaxy. The activation energies of holes in these QWs are studied by deep-level transient spectroscopy. It is observed that the holes activation energies increase monotonically with the Sn fraction (x). The valence band offset between pseudomorphic Si1-x Sn x and Si obeys the dependence ΔE(v) = 1.69x eV, while the offset between the average valence bands of unstrained Si1-x Sn x /Si heterojunction was deduced and obeys the dependence ΔE(v(av)) = 1.27x eV.

16.
Clin Chem Lab Med ; 54(9): 1503-10, 2016 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-26910746

RESUMO

BACKGROUND: The distinction between reactive and neoplastic leukocytes, especially atypical lymphocytes suspected to be reactive or neoplastic, is a particular challenge in automated hematological cell differentiation. The aim of the study was to evaluate the performance of the XN analyzer supplemented with the WPC channel for differentiating between reactive and neoplastic leukocytosis. METHODS: Blood samples of 253 patients with viral infections, lymphoma or leukemia were analyzed by the Sysmex XN-2000 analyzer equipped with the WPC channel. The results were compared to routine leukocyte differentiation using the routine Sysmex XE-2100 analyzer and automated digital microscopy (DM96). The combined information from standard morphology, immune phenotyping and clinical diagnosis served as a reference. RESULTS: The XN WPC channel demonstrated an excellent performance for differentiating neoplastic (AUC=0.933) and reactive leukocytosis (AUC=0.900) as compared to morphological smear examination (AUC=0.949 and AUC=0.968, respectively) or to the differentiation results of our routine hematology analyzer (AUC=0.630 and AUC=0.635, respectively). CONCLUSIONS: Our data show that the combined WDF/WPC of the Sysmex XN-Series analyzer is advantageous in the automated differentiation of neoplastic and reactive leukocytosis, thus supporting the correct diagnostic decision in the daily laboratory routine.


Assuntos
Contagem de Células/instrumentação , Leucemia/diagnóstico , Leucócitos/patologia , Leucocitose/diagnóstico , Leucocitose/patologia , Linfoma/diagnóstico , Automação , Diferenciação Celular , Humanos , Leucemia/sangue , Leucemia/patologia , Leucocitose/sangue , Leucocitose/virologia , Linfoma/sangue , Linfoma/patologia , Viroses/sangue , Viroses/diagnóstico , Viroses/patologia
17.
J Struct Biol ; 191(2): 165-74, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26094876

RESUMO

We report on a structural analysis of several basal spicules of the deep-sea silica sponge Monorhaphis chuni by electron microscope techniques supported by a precise focused ion beam (FIB) target preparation. To get a deeper understanding of the spicules length growth, we concentrated our investigation onto the apical segments of two selected spicules with apparently different growth states and studied in detail permanent and temporary growth structures in the central compact silica axial cylinder (AC) as well as the structure of the organic axial filament (AF) in its center. The new findings concern the following morphology features: (i) at the tip we could identify thin silica layers, which overgrow as a tongue-like feature the front face of the AC and completely fuse during the subsequent growth state. This basically differs from the radial growth of the surrounding lamellar zone of the spicules made of alternating silica lamellae and organic interlayers. (ii) A newly detected disturbed cylindrical zone in the central region of the AC (diameter about 30 µm) contains vertical and horizontal cavities, channels and agglomerates, which can be interpreted as permanent leftover of a formerly open axial channel, later filled by silica. (iii) The AF consists of a three-dimensional crystal-like arrangement of organic molecules and amorphous silica surrounding these molecules. Similar to an inorganic crystal, this encased protein crystal is typified by crystallographic directions, lattice planes and surface steps. The 〈001〉 growth direction is especially favored, thereby scaffolding the axial cylinders growth and consequently the spicules' morphology.


Assuntos
Poríferos/ultraestrutura , Dióxido de Silício/química , Animais , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Espectrometria por Raios X
18.
Small ; 11(42): 5636-41, 2015 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-26366879

RESUMO

The formation mechanism of a perfectly ordered protein/silica structure in the axial filament of the anchor spicule of the silica sponge Monorhaphis chuni is suggested. Experimental evidence shows that the growth of this architecture is realized by a thermodynamically driven dislocation-mediated spiral growth mechanism, resulting in a specific rotation of the mesoscopic crystal lattice (Eshelby twist).


Assuntos
Proteínas da Matriz Extracelular/química , Proteínas da Matriz Extracelular/metabolismo , Conformação Molecular , Poríferos/metabolismo , Dióxido de Silício/química , Animais , Cristalização , Tomografia com Microscopia Eletrônica , Rotação , Difração de Raios X
19.
Nanotechnology ; 26(24): 245301, 2015 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-26011398

RESUMO

A systematic method to control the porosity of silicon nanowires is presented. This method is based on metal-assisted chemical etching (MACE) and takes advantage of an HF/H2O2 etching solution and a silver catalyst in the form of a thin patterned film deposited on a doped silicon wafer. It is found that the porosity of the etched nanowires can be controlled by the doping level of the wafer. For low doping concentrations, the wires are primarily crystalline and surrounded by only a very thin layer of porous silicon (pSi) layer, while for highly doped silicon, they are porous in their entire volume. We performed a series of controlled experiments to conclude that there exists a well-defined critical doping concentration separating the crystalline and porous regimes. Furthermore, transmission electron microscopy investigations showed that the pSi has also a crystalline morphology on a length scale smaller than the pore size, determined from positron annihilation lifetime spectroscopy to be mesoscopic. Based on the experimental evidence, we devise a theoretical model of the pSi formation during MACE and apply it for better control of the nanowire morphology.

20.
Heart Surg Forum ; 18(3): E090-2, 2015 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-26115150

RESUMO

Thrombocytopenia might be an exclusion criterion for invasive radiofrequency catheter ablation; therefore it is necessary to differentiate between pseudo-thrombocytopenia and a low platelet count due to other etiologies.A 69-year-old female presented to the cardiology department with recurrent atrial fibrillation that was resistant to conventional drug treatment. The initial laboratory findings were within the normal ranges, except for low platelet counts that occurred without a specific bleeding history. The reason for thrombocytopenia was anticoagulant-induced in vitro aggregation of platelets in the presence of EDTA as well as in citrated blood samples. As recently communicated, magnesium anticoagulated blood samples prevent platelet aggregation in individuals with anticoagulant-associated pseudo-thrombocytopenia. Although its aggregation-inhibiting effect is known from previous clinical observations, magnesium sulphate has not been introduced as an anticoagulant in analytical medicine.Based on our observations, blood anticoagulated with magnesium sulphate is recommended to verify low routine platelet counts before final clinical decisions are made.


Assuntos
Anticoagulantes/uso terapêutico , Fibrilação Atrial/cirurgia , Ablação por Cateter , Sulfato de Magnésio/uso terapêutico , Trombocitopenia/diagnóstico , Idoso , Anticoagulantes/efeitos adversos , Contraindicações , Ácido Edético/efeitos adversos , Ácido Edético/uso terapêutico , Feminino , Humanos , Agregação Plaquetária/efeitos dos fármacos , Contagem de Plaquetas , Recidiva , Trombocitopenia/induzido quimicamente
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