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The self-assembly of block copolymers with large feature sizes is inherently challenging as the large kinetic barrier arising from chain entanglement of high molecular weight (MW) polymers limits the extent over which long-range ordered microdomains can be achieved. Here, we illustrate the evolution of thin film morphology from a diblock copolymer of polystyrene-block-poly(dimethylsiloxane) exhibiting total number average MW of 123 kg mol-1, and demonstrate the formation of layers of well-ordered cylindrical microdomains under appropriate conditions of binary solvent mix ratio, commensurate film thickness, and solvent vapor annealing time. Directed self-assembly of the block copolymer within lithographically patterned trenches occurs with alignment of cylinders parallel to the sidewalls. Fabrication of ordered cobalt nanowire arrays by pattern transfer was also implemented, and their magnetic properties and domain wall behavior were characterized.
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Magnetophotonic crystals (MPCs) comprising cerium-substituted yttrium iron garnet (CeYIG) sandwiched by two Bragg mirrors were fabricated by vacuum annealing. CeYIG was deposited on Bragg mirrors at room temperature and annealed in 5 Pa of residual air. No ceria or other non-garnet phases were detected. Cerium 3 + ions substituted on the yttrium sites and no cerium 4 + ions were found. The Faraday rotation angle of the MPC was -2.92° at a wavelength of λ = 1570 nm was 30 times larger than that of the CeYIG film. These results showed good agreement with calculated values derived using a matrix approach.
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The response of polystyrene-block-poly(dimethylsiloxane) (PS-b-PDMS) thin films to UV exposure during solvent vapor annealing is described, in order to improve their applicability in nanolithography and nanofabrication. Two BCPs were examined, one with the PS block as majority (f PS = 68%, M n = 53 kg mol-1), the other with PDMS block as majority (f PDMS = 67%, M n = 44 kg mol-1). A 5 min UV irradiation was applied during solvent vapor annealing which led to both partial crosslinking of the polymer and a small increase in the temperature of the annealing chamber. This approach was effective for improving the correlation length of the self-assembled microdomain arrays and in limiting subsequent flow of the PDMS in the PDMS-majority BCP to preserve the post-anneal morphology. Ordering and orientation of microdomains were controlled by directed self-assembly of the BCPs in trench substrates. Highly-ordered perpendicular nanochannel arrays were obtained in the PDMS-majority BCP.
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PURPOSE: Huntington disease (HD) is a chronic, debilitating genetic disease that affects physical, emotional, cognitive, and social health. Existing patient-reported outcomes (PROs) of health-related quality of life (HRQOL) used in HD are neither comprehensive, nor do they adequately account for clinically meaningful changes in function. While new PROs examining HRQOL (i.e., Neuro-QoL-Quality of Life in Neurological Disorders and PROMIS-Patient-Reported Outcomes Measurement Information System) offer solutions to many of these shortcomings, they do not include HD-specific content, nor have they been validated in HD. HDQLIFE addresses this by validating 12 PROMIS/Neuro-QoL domains in individuals with HD and by using established PROMIS methodology to develop new, HD-specific content. METHODS: New item pools were developed using cognitive debriefing with individuals with HD, and expert, literacy, and translatability reviews. Existing item banks and new item pools were field tested in 536 individuals with prodromal, early-, or late-stage HD. RESULTS: Moderate to strong relationships between Neuro-QoL/PROMIS measures and generic self-report measures of HRQOL, and moderate relationships between Neuro-QoL/PROMIS and clinician-rated measures of similar constructs supported the validity of Neuro-QoL/PROMIS in individuals with HD. Exploratory and confirmatory factor analysis, item response theory, and differential item functioning analyses were utilized to develop new item banks for Chorea, Speech Difficulties, Swallowing Difficulties, and Concern with Death and Dying, with corresponding six-item short forms. A four-item short form was developed for Meaning and Purpose. CONCLUSIONS: HDQLIFE encompasses both validated Neuro-QoL/PROMIS measures, as well as five new scales in order to provide a comprehensive assessment of HRQOL in HD.
Assuntos
Doença de Huntington/psicologia , Perfil de Impacto da Doença , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e QuestionáriosRESUMO
Cobalt-substituted SrTiO3 films (SrTi0.70Co0.30O(3-δ)) were grown on SrTiO3 substrates using pulsed laser deposition under oxygen pressures ranging from 1 µTorr to 20 mTorr. The effect of oxygen pressure on structural, magnetic, optical, and magneto-optical properties of the films was investigated. The film grown at 3 µTorr has the highest Faraday rotation (FR) and magnetic saturation moment (M(s)). Increasing oxygen pressure during growth reduced M(s), FR and optical absorption in the near-infrared. This trend is attributed to decreasing Co2+ ion concentration and oxygen vacancy concentration with higher oxygen partial pressure during growth.
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Recent progress in modelling the solvent vapor annealing of thin film block copolymers is examined in the context of a self-consistent field theory framework. Key control variables in determining the final microdomain morphologies include swelling ratio or swollen film solvent volume fraction, swollen film thickness, substrate and vapor atmosphere surface energies, effective volume fraction, and effective Flory-Huggins interaction parameter. The regime of solvent vapor annealing studied is where the block copolymer has a high enough Flory-Huggins parameter that ordered structures form during swelling and are then trapped in the system through quenching. Both implicit and explicit consideration of the solvent vapor is considered to distinguish the cases in which solvent vapor leads to a non-bulk morphology. Block-selective solvents are considered based on the experimental systems of polystyrene-b-polydimethylsiloxane annealed with toluene and heptane. The results of these simulations are compared with these experiments.
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Two-phase nanocomposite films consisting of metallic Co nanoparticles below 50 nm diameter in a perovskite matrix were grown by pulsed laser deposition onto (LaAlO3)0.3(Sr2AlTaO6)0.7 (LSAT) and silicon substrates from a target of SrGa0.73Co0.27O3. The particles made up about 6% by volume of the film and were present within the film and at the substrate interface. The saturation magnetization of the film was up to 85 emu cm(-3) at 80 nm thickness and the Faraday rotation (FR) tracked the out-of-plane hysteresis loop, reaching 3000 deg cm(-1) at 10 kOe for 1550 nm wavelength. The magneto-optical figure of merit defined as FR divided by optical absorption was 0.04-0.06 deg dB(-1) due to the high optical absorption of the Co particles.
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Cerium substituted yttrium iron garnet (Ce:YIG) films were grown on yttrium iron garnet (YIG) seed layers on silicon nitride films using pulsed laser deposition. Optimal process conditions for forming garnet films on silicon nitride are presented. Bulk or near-bulk magnetic and magneto-optical properties were observed for 160 nm thick Ce:YIG films grown at 640 °C on rapid thermal annealed 40 nm thick YIG grown at 640 °C and 2 Hz pulse rate. The effect of growth temperature and deposition rate on structural, magnetic and magneto-optical properties has been investigated.
Assuntos
Cério/química , Compostos de Ferro/química , Fenômenos Magnéticos , Fenômenos Ópticos , Fótons , Compostos de Silício/química , Ítrio/química , Microscopia de Força Atômica , Microscopia Eletrônica de Transmissão , Espectrometria por Raios X , Temperatura , Difração de Raios XRESUMO
Vacuum annealed polycrystalline cerium substituted yttrium iron garnet (CeYIG) films deposited by radio frequency magnetron sputtering on non-garnet substrates were used in nonreciprocal racetrack resonators. CeYIG annealed at 800°C for 30 min provided a large Faraday rotation angle, close to the single crystal value. Crystallinity, magnetic properties, refractive indices and absorption coefficients were measured. The resonant transmission peak of the racetrack resonator covered with CeYIG was non-reciprocally shifted by applying an in-plane magnetic field.
RESUMO
A two-stage annealing process for block copolymer films was introduced consisting of a solvent vapor exposure followed by a thermal cycle. By heating the film but not the chamber, changes in the ambient vapor pressure of the solvent were avoided. Films of block copolymers and homopolymers showed transient nonmonotonic swelling behavior immediately after solvent exposure that was dependent on how the thin film was cast before the anneal. Thermal cycling of the solvent-swelled block copolymer films during the solvent vapor anneal (SVA) caused the films to deswell in 1-10 s and produced well-ordered microdomains in templated 45.5 and 51.5 kg/mol polystyrene-block-polydimethylsiloxane films annealed in toluene and n-heptane vapors for total process times of 30 s to 5 min.
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Microsatellite DNA sequences are rapidly becoming the dominant source of nuclear genetic markers for a wide range of applications, from genome mapping to forensic testing to population studies. If misinterpretation is to be avoided, it is vital that we understand fully the way in which microsatellite sequences evolve. We have therefore compared allele length distributions for 42 microsatellites in humans with their homologues in a range of related primates. We find a highly significant trend for the loci to be longer in humans, showing that microsatellites can evolve directionally and at different rates in closely related species.
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Evolução Biológica , DNA Satélite/genética , Alelos , Animais , Sequência de Bases , Primers do DNA/genética , Marcadores Genéticos , Humanos , Modelos Genéticos , Dados de Sequência Molecular , Mutação , Pan troglodytes/genética , Reação em Cadeia da Polimerase , Primatas/genética , Sequências Repetitivas de Ácido Nucleico , Seleção Genética , Especificidade da EspécieRESUMO
We recently described a disorder termed Huntington disease-like 2 (HDL2) that completely segregates with an unidentified CAG/CTG expansion in a large pedigree (W). We now report the cloning of this expansion and its localization to a variably spliced exon of JPH3 (encoding junctophilin-3), a gene involved in the formation of junctional membrane structures.
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Doença de Huntington/genética , Proteínas de Membrana/genética , Repetições de Trinucleotídeos , Sequência de Bases , Clonagem Molecular , Feminino , Humanos , Masculino , Dados de Sequência Molecular , LinhagemRESUMO
Parkinson disease (PD) is a neurodegenerative disease characterized by tremor, bradykinesia, rigidity and postural instability. Post-mortem examination shows loss of neurons and Lewy bodies, which are cytoplasmic eosinophilic inclusions, in the substantia nigra and other brain regions. A few families have PD caused by mutations (A53T or A30P) in the gene SNCA (encoding alpha-synuclein). Alpha-synuclein is present in Lewy bodies of patients with sporadic PD, suggesting that alpha-synuclein may be involved in the pathogenesis of PD. It is unknown how alpha-synuclein contributes to the cellular and biochemical mechanisms of PD, and its normal functions and biochemical properties are poorly understood. To determine the protein-interaction partners of alpha-synuclein, we performed a yeast two-hybrid screen. We identified a novel interacting protein, which we term synphilin-1 (encoded by the gene SNCAIP). We found that alpha-synuclein interacts in vivo with synphilin-1 in neurons. Co-transfection of both proteins (but not control proteins) in HEK 293 cells yields cytoplasmic eosinophilic inclusions.
Assuntos
Proteínas de Transporte/metabolismo , Corpos de Inclusão/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Sequência de Aminoácidos , Animais , Química Encefálica , Proteínas de Transporte/genética , Linhagem Celular , Cromossomos Humanos Par 5/genética , Feminino , Humanos , Corpos de Lewy/metabolismo , Masculino , Dados de Sequência Molecular , Proteínas do Tecido Nervoso/genética , Doença de Parkinson/genética , Doença de Parkinson/metabolismo , Plasmídeos/genética , Ligação Proteica , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Saccharomyces cerevisiae/genética , Homologia de Sequência de Aminoácidos , Sinucleínas , Distribuição Tecidual , Extratos de Tecidos/metabolismo , Transfecção , alfa-SinucleínaRESUMO
An important part of meeting nutrient reduction goals in the lower Great Lakes basin and assessing the success of different land management strategies is modeling nutrient losses from agricultural land. This study aimed to improve the representation of water source contributions to streamflow in generalized additive models for predicting nutrient fluxes from three headwater agricultural streams in southern Ontario monitored during the Multi-Watershed Nutrient Study (MWNS). The previous development of these models represented baseflow contributions to streamflow using the baseflow proportion derived using an uncalibrated recursive digital filter. Recursive digital filters are commonly used to partition stream discharge into separate components from slower and faster pathways. In this study, we calibrated the recursive digital filter using stream water source information from stable isotopes of oxygen in water. Across sites, optimization of the filter parameters reduced bias in baseflow estimates by as much as 68 %. In most cases, calibrating the filter also improved agreement between filter-derived baseflow and baseflow calculated from isotope and streamflow data: the average Kling-Gupta Efficiencies using default and calibrated parameters were 0.44 and 0.82, respectively. When incorporated into the generalized additive models, the revised baseflow proportion predictor was more often statistically significant, improved model parsimony, and reduced prediction uncertainty. Moreover, this information allowed for a more rigorous interpretation of how different stream water sources influence nutrient losses from the agricultural MWNS watersheds.
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Movimentos da Água , Água , Agricultura , Lagos , Isótopos , Monitoramento AmbientalRESUMO
AIMS: The pathogenesis of obesity remains incompletely understood and the exploration of the role of novel proteins in obesity may provide important insights into its causes and treatments. Here, we report a previously unidentified role for synphilin-1 in the control of food intake and body weight. Synphilin-1, a cytoplasmic protein, was initially identified as an interaction partner of alpha-synuclein, and has implications in Parkinson's disease pathogenesis related to protein aggregation. SUBJECTS AND METHODS: To study the in vivo role of synphilin-1, we characterized a human synphilin-1 transgenic mouse (SP1) by assessing synphilin-1 expression, plasma parameters, food intake and spontaneous activity to determine the major behavioral changes and their consequences in the development of the obesity phenotype. RESULTS: Expression of human synphilin-1 in brain neurons in SP1 mice resulted in increased food intake, body weight and body fat. SP1 mice also displayed hyperinsulinemia, hyperleptinemia and impaired glucose tolerance. Pair-feeding SP1 mice to amounts consumed by non-transgenic mice prevented the increased body weight, adiposity, hyperinsulinemia and hyperleptinemia demonstrating that these were all the consequences of increased food intake. Transgenic expression of synphilin-1 was enriched in hypothalamic nuclei involved in feeding control, and fasting-induced elevated endogenous synphilin-1 levels at these sites, suggesting that synphilin-1 is an important player in the hypothalamic energy balance regulatory system. CONCLUSION: These studies identify a novel function of synphilin-1 in controlling food intake and body weight, and may provide a unique obesity model for future studies of obesity pathogenesis and therapeutics.
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Proteínas de Transporte/metabolismo , Ingestão de Alimentos/efeitos dos fármacos , Hiperfagia/metabolismo , Hipotálamo/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Obesidade/metabolismo , Animais , Western Blotting , Peso Corporal , Proteínas de Transporte/genética , Proteínas de Transporte/farmacologia , Modelos Animais de Doenças , Hipotálamo/efeitos dos fármacos , Imuno-Histoquímica , Peptídeos e Proteínas de Sinalização Intracelular , Camundongos , Camundongos Transgênicos , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/farmacologiaRESUMO
Thin films of polycrystalline cerium substituted yttrium iron garnet (CeYIG) were grown on an yttrium iron garnet (YIG) seed layer on Si and Si-on-insulator substrates by pulsed laser deposition, and their optical and magneto-optical properties in the near-IR region were measured. A YIG seed layer of ~30 nm thick processed by rapid thermal anneal at 800°C provided a virtual substrate to promote crystallization of the CeYIG. The effect of the thermal budget of the YIG/CeYIG growth process on the film structure, magnetic and magnetooptical properties was determined.
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Césio/química , Ferro/química , Membranas Artificiais , Semicondutores , Ítrio/química , Condutividade Elétrica , Transferência de Energia , Temperatura Alta , Campos Magnéticos , Teste de Materiais , RefratometriaRESUMO
Strong genetic evidence implicates mutations and polymorphisms in the gene Disrupted-In-Schizophrenia-1 (DISC1) as risk factors for both schizophrenia and mood disorders. Recent studies have shown that DISC1 has important functions in both brain development and adult brain function. We have described earlier a transgenic mouse model of inducible expression of mutant human DISC1 (hDISC1) that acts in a dominant-negative manner to induce the marked neurobehavioral abnormalities. To gain insight into the roles of DISC1 at various stages of neurodevelopment, we examined the effects of mutant hDISC1 expressed during (1) only prenatal period, (2) only postnatal period, or (3) both periods. All periods of expression similarly led to decreased levels of cortical dopamine (DA) and fewer parvalbumin-positive neurons in the cortex. Combined prenatal and postnatal expression produced increased aggression and enhanced response to psychostimulants in male mice along with increased linear density of dendritic spines on neurons of the dentate gyrus of the hippocampus, and lower levels of endogenous DISC1 and LIS1. Prenatal expression only resulted in smaller brain volume, whereas selective postnatal expression gave rise to decreased social behavior in male mice and depression-like responses in female mice as well as enlarged lateral ventricles and decreased DA content in the hippocampus of female mice, and decreased level of endogenous DISC1. Our data show that mutant hDISC1 exerts differential effects on neurobehavioral phenotypes, depending on the stage of development at which the protein is expressed. The multiple and diverse abnormalities detected in mutant DISC1 mice are reminiscent of findings in major mental diseases.
Assuntos
Encéfalo , Regulação da Expressão Gênica no Desenvolvimento/genética , Transtornos Mentais/genética , Mutação/genética , Proteínas do Tecido Nervoso/metabolismo , Fatores Etários , Anfetamina , Análise de Variância , Animais , Animais Recém-Nascidos , Comportamento Animal , Encéfalo/embriologia , Encéfalo/crescimento & desenvolvimento , Encéfalo/patologia , Encéfalo/ultraestrutura , Proteínas de Transporte/metabolismo , Cromatografia Líquida de Alta Pressão/métodos , Modelos Animais de Doenças , Maleato de Dizocilpina , Dopamina/metabolismo , Técnicas Eletroquímicas/métodos , Embrião de Mamíferos , Comportamento Exploratório/fisiologia , Feminino , Humanos , Locomoção/efeitos dos fármacos , Locomoção/genética , Imageamento por Ressonância Magnética , Masculino , Aprendizagem em Labirinto/fisiologia , Camundongos , Camundongos Transgênicos , Proteínas do Tecido Nervoso/genética , Parvalbuminas/metabolismo , Fenótipo , Gravidez , Coloração pela Prata/métodosRESUMO
OBJECTIVE: Catatonia is considered a unique syndrome of motor signs, at times life-threatening when aggravated by autonomic dysfunction and fever, but eminently treatable with specific medical treatments, if recognized early. Catatonia commonly occurs in children and adolescents with a wide range of associated disorders. The role of deprivation, abuse, or trauma in the development of pediatric catatonia is examined. METHOD: Reports considering deprivation, abuse, or trauma as precipitants of catatonia in pediatric cases are culled from the classic writings on catatonia and from a selective review of modern contributions. RESULTS: Kahlbaum gave trauma a central role in catatonia in many young adult cases. Kanner described children with psychogenic catalepsy. Anaclitic depression, a condition found by Spitz in deprived institutionalized children, strongly resembles stuporous catatonia. Leonhard considered lack of communication with the mother or substitute mother as an important risk factor for childhood catatonia. Children including those with autism who experience emotional and physical trauma sometimes develop catatonia. The clinical descriptions of children with classic catatonic syndromes and those of contemporary refugee children with a syndrome labeled Pervasive Refusal Syndrome are similar. CONCLUSION: The literature supports the view that deprivation, abuse, and trauma can precipitate catatonia in children and adolescents.
Assuntos
Transtorno Autístico/diagnóstico , Catatonia , Maus-Tratos Infantis/psicologia , Desenvolvimento Infantil , Relações Mãe-Filho , Adolescente , Catatonia/diagnóstico , Catatonia/tratamento farmacológico , Catatonia/etiologia , Catatonia/psicologia , Criança , Criança Institucionalizada/psicologia , Diagnóstico Diferencial , Diagnóstico Precoce , Intervenção Médica Precoce , Humanos , Acontecimentos que Mudam a Vida , Fatores Desencadeantes , Psicopatologia , Carência Psicossocial , Fatores de RiscoRESUMO
The structure and magnetic properties of epitaxial (Ce(x)Sr(1-x))(Ti(0.6)Fe(0.4))O(3-δ) (x = 0, 0.1, 0.2 and 0.3) and (La(x)Sr(1-x))(Ti(0.6)Fe(0.4))O(3-δ) (x = 0, 0.1, 0.2, 0.3 and 0.4) perovskite-structure thin films deposited by pulsed laser deposition on (LaAlO(3))(0.3)(Sr(2)AlTaO(6))(0.7) (LSAT) substrates are reported. Both La and Ce ions showed a dominant 3+ valence state and acted as donors on the Sr(2+) site (A site) in the perovskite lattice. The optical band gap widened, and the Fermi level moved toward the vacuum level with increased Ce or La content; meanwhile the Ti and particularly the Fe ions were driven to a lower valence state, resulting in a higher Fe(2+) concentration. The materials were magnetic at room temperature with up to 0.8 µ(B)/Fe and a magnetoelastic out-of-plane anisotropy. Ce and La lowered the coercivity while raising both the Faraday rotation at 1550 nm and the optical absorption at near-infrared wavelengths.
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An extraordinarily large degree of tunability in geometry and dimension is demonstrated in films of a self-assembled block copolymer. A poly(2-vinylpyridine-b-dimethylsiloxane) block copolymer with highly incompatible blocks was spun-cast on patterned substrates and treated with various solvent vapors. The degree of selective swelling in the poly(2-vinylpyridine) matrix block could be controlled over an extensive range, leading to the formation of various microdomain morphologies such as spheres, cylinders, hexagonally perforated lamellae, and lamellae from the same block copolymer. The systematic control of swelling ratio and the choice of solvent vapors offer the unusual ability to control the width of very well-ordered linear features within a range between 6 and 31 nm. This methodology is particularly useful for nanolithography based on directed self-assembly in that a single block copolymer film can form microdomains with a broad range of geometries and sizes without the need to change molecular weight or volume fraction.