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1.
Nanotechnology ; 34(14)2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36595322

RESUMO

Self-assembled quantum dots (QDs) based on III-V semiconductors have excellent properties for applications in quantum optics. However, the presence of a 2D wetting layer (WL) which forms during the Stranski-Krastanov growth of QDs can limit their performance. Here, we investigate WL formation during QD growth by the droplet epitaxy technique. We use a combination of photoluminescence excitation spectroscopy, lifetime measurements, and transmission electron microscopy to identify the presence of an InGaAs WL in these droplet epitaxy QDs, even in the absence of distinguishable WL luminescence. We observe that increasing the amount of Ga deposited on a GaAs (100) surface prior to the growth of InGaAs QDs leads to a significant reduction in the emission wavelength of the WL to the point where it can no longer be distinguished from the GaAs acceptor peak emission in photoluminescence measurements. However increasing the amount of Ga deposited does not suppress the formation of a WL under the growth conditions used here.


Assuntos
Arsenicais , Gálio , Pontos Quânticos , Arsenicais/química , Luminescência , Gálio/química
2.
Nature ; 519(7543): 331-3, 2015 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-25788096

RESUMO

Gas clouds in present-day galaxies are inefficient at forming stars. Low star-formation efficiency is a critical parameter in galaxy evolution: it is why stars are still forming nearly 14 billion years after the Big Bang and why star clusters generally do not survive their births, instead dispersing to form galactic disks or bulges. Yet the existence of ancient massive bound star clusters (globular clusters) in the Milky Way suggests that efficiencies were higher when they formed ten billion years ago. A local dwarf galaxy, NGC 5253, has a young star cluster that provides an example of highly efficient star formation. Here we report the detection of the J = 3→2 rotational transition of CO at the location of the massive cluster. The gas cloud is hot, dense, quiescent and extremely dusty. Its gas-to-dust ratio is lower than the Galactic value, which we attribute to dust enrichment by the embedded star cluster. Its star-formation efficiency exceeds 50 per cent, tenfold that of clouds in the Milky Way. We suggest that high efficiency results from the force-feeding of star formation by a streamer of gas falling into the galaxy.

3.
Horm Behav ; 124: 104777, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32439347

RESUMO

Neuropeptide oxytocin (OT) is involved in the regulation of social and non-social behaviour. The central nucleus of amygdala (CeA), part of the limbic system, plays an important role in learning, memory, anxiety and reinforcing mechanisms. CeA has been shown to be rich in OT receptors in rodents. Our previous findings indicated that OT in the rat CeA has a dose dependent rewarding and anxiolytic effect. The aim of our present study was to examine in the CeA the possible interaction of OT and D2 dopamine (DA) receptor antagonist Sulpiride on reinforcement in place preference test and on anxiety in elevated plus maze test. Wistar rats were microinjected bilaterally with 10 ng OT. In different group of animals 4 µg D2 DA receptor antagonist was applied. Other animals received D2 DA receptor antagonist 15 min before 10 ng OT treatment or vehicle solution into the CeA. Rats receiving 10 ng OT spent significantly longer time in the treatment quadrant during the test session in conditioned place preference test. Prior treatment with D2 DA receptor antagonist blocked the rewarding effects of OT. Antagonist in itself did not influence the time rats spent in the treatment quadrant. In elevated plus maze test, rats receiving 10 ng OT spent significantly longer time on the open arms. Prior treatment with D2 DA receptor antagonist blocked the effects of OT. Our results show that DA system plays a role in positive reinforcing and anxiolytic effects of OT because D2 DA receptor antagonist can block these actions.


Assuntos
Ansiolíticos/farmacologia , Ocitocina/farmacologia , Receptores de Dopamina D2/fisiologia , Comportamento Espacial/efeitos dos fármacos , Tonsila do Cerebelo/efeitos dos fármacos , Tonsila do Cerebelo/metabolismo , Animais , Ansiedade/tratamento farmacológico , Comportamento Animal/efeitos dos fármacos , Condicionamento Clássico/efeitos dos fármacos , Antagonistas dos Receptores de Dopamina D2/farmacologia , Medo/efeitos dos fármacos , Reação de Congelamento Cataléptica/efeitos dos fármacos , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Ratos , Ratos Wistar , Receptores de Dopamina D1/metabolismo , Receptores de Dopamina D2/metabolismo , Receptores de Ocitocina/metabolismo , Receptores de Ocitocina/fisiologia , Reforço Psicológico , Recompensa , Sulpirida/farmacologia
4.
J Microsc ; 279(3): 217-221, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31985824

RESUMO

The growth of cobalt nanopatterns (NPs) using focused electron-beam induced deposition (FEBID) for localised magnetic studies is presented. The initial FEBID products are shown to be polycrystalline and form hetero-structured core-shell NPs through surface oxidation. Off-axis electron holography is performed to reconstruct their morphology, thickness profile and image their individual magnetic vortex domain states. In situ annealing to 400°C promoted migration of the Co-overspray to grow the Co NPs and improved their crystallinity through coarsening, as well as induced diffusion of embedded carbon out of their surface. It is found that the change in their morphology and chemical instability under heating restricts their suitability for examining thermally induced magnetic variations. LAY DESCRIPTION: In this paper, electron microscopy is used to deposit magnetic cobalt nanopatterns and characterise the effect of in-situ heating on their chemistry, structure and magnetic properties. The electron beam of the secondary electron microscope is used to dissociate an injected precursor gas near the SiN membrane substrate of in-situ transmission electron microscopy (TEM) chips and locally deposit the elemental Co in circular patterns ∼ 90 nm in diameter. TEM reveals formation of a Co-oxide shell and embedding of carbon from the precursor gas during growth. The technique of electron holography is used to image the magnetism of the core-shell Co / Co-oxide nanopatterns, which are shown to exhibit magnetic vortex states. In-situ annealing results in migration of the Co overspray to increase their height and carbon diffusion from their surface, as well as change in their original magnetic state through change of orientation. It is found that the change in the morphology and chemistry of Co nanopatterns under heating limits their use for studying the effect of temperature on their magnetism in isolation.

5.
Eur Arch Psychiatry Clin Neurosci ; 270(6): 645-653, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31175448

RESUMO

To identify factors associated with the use of shared decision making in routine mental health care in a large multicenter European study. Data have been collected within the study "Clinical decision making and outcome in routine care for people with severe mental illness" (CEDAR), which is a naturalistic, longitudinal, observational study carried out in six European countries. Patients with a severe mental illness attending outpatient units and their treating clinicians have been recruited. Clinicians' Clinical Decision Making (CDM) styles have been explored through the Clinical Decision Making Style Scale. Patients' clinical and social outcomes have been assessed through validated assessment instruments. The sample consisted of 588 patients and 213 professionals. Professionals were mainly psychiatrists (35.7%), nurses (21.6%), support workers, social workers or occupational therapists (24.9%), psychologists (9.9%) or trainees in psychiatry (4.7%). In the majority of cases, clinicians adopted a shared CDM style. Shared CDM was more frequently adopted with patients with psychotic disorders, with a better quality of life and social functioning. At multivariate analyses, the likelihood of adopting shared decision making increased in patients with higher levels of interpersonal relationships' skills (p < 0.05) and global functioning (p < 0.01). On the contrary, being a trainee in psychiatry reduced the likelihood of adopting shared CDM (p < 0.008). Shared decision making has been adopted mainly when patients have a better functioning and less severe clinical symptomatology and by less trained clinicians, differently from national and international recommendations. More efforts should be made to implement interventions to promote shared CDM, with a specific focus for trainees in psychiatry.


Assuntos
Atitude do Pessoal de Saúde , Tomada de Decisão Clínica , Tomada de Decisão Compartilhada , Transtornos Mentais/terapia , Serviços de Saúde Mental , Avaliação de Processos em Cuidados de Saúde , Relações Profissional-Paciente , Psiquiatria/métodos , Adulto , Assistência Ambulatorial , Europa (Continente) , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Psiquiatria/educação , Funcionamento Psicossocial , Transtornos Psicóticos/terapia , Qualidade de Vida , Habilidades Sociais
6.
Cell Mol Life Sci ; 76(14): 2799-2815, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30734834

RESUMO

The pedunculopontine nucleus (PPN) is a part of the reticular activating system which is composed of cholinergic, glutamatergic and GABAergic neurons. Early electrophysiological studies characterized and grouped PPN neurons based on certain functional properties (i.e., the presence or absence of the A-current, spike latency, and low threshold spikes). Although other electrophysiological characteristics of these neurons were also described (as high threshold membrane potential oscillations, great differences in spontaneous firing rate and the presence or absence of the M-current), systematic assessment of these properties and correlation of them with morphological markers are still missing. In this work, we conducted electrophysiological experiments on brain slices of genetically identified cholinergic neurons in the PPN. Electrophysiological properties were compared with rostrocaudal location of the neuronal soma and selected morphometric features obtained with post hoc reconstruction. We found that functional subgroups had different proportions in the rostral and caudal subregions of the nucleus. Neurons with A-current can be divided to early-firing and late-firing neurons, where the latter type was found exclusively in the caudal subregion. Similar to this, different parameters of high threshold membrane potential oscillations also showed characteristic rostrocaudal distribution. Furthermore, based on our data, we propose that high threshold oscillations rather emerge from neuronal somata and not from the proximal dendrites. In summary, we demonstrated the existence and spatial distribution of functional subgroups of genetically identified PPN cholinergic neurons, which are in accordance with differences found in projection and in vivo functional findings of the subregions. Being aware of functional differences of PPN subregions will help the design and analysis of experiments using genetically encoded opto- and chemogenetic markers for in vivo experiments.


Assuntos
Acetilcolina/metabolismo , Potenciais de Ação , Neurônios Colinérgicos/fisiologia , Núcleo Tegmental Pedunculopontino/fisiologia , Animais , Potenciais da Membrana , Camundongos , Camundongos Transgênicos , Ratos
7.
Nature ; 496(7445): 329-33, 2013 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-23598341

RESUMO

Massive present-day early-type (elliptical and lenticular) galaxies probably gained the bulk of their stellar mass and heavy elements through intense, dust-enshrouded starbursts--that is, increased rates of star formation--in the most massive dark-matter haloes at early epochs. However, it remains unknown how soon after the Big Bang massive starburst progenitors exist. The measured redshift (z) distribution of dusty, massive starbursts has long been suspected to be biased low in z owing to selection effects, as confirmed by recent findings of systems with redshifts as high as ~5 (refs 2-4). Here we report the identification of a massive starburst galaxy at z = 6.34 through a submillimetre colour-selection technique. We unambiguously determined the redshift from a suite of molecular and atomic fine-structure cooling lines. These measurements reveal a hundred billion solar masses of highly excited, chemically evolved interstellar medium in this galaxy, which constitutes at least 40 per cent of the baryonic mass. A 'maximum starburst' converts the gas into stars at a rate more than 2,000 times that of the Milky Way, a rate among the highest observed at any epoch. Despite the overall downturn in cosmic star formation towards the highest redshifts, it seems that environments mature enough to form the most massive, intense starbursts existed at least as early as 880 million years after the Big Bang.

8.
Nano Lett ; 18(2): 964-970, 2018 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-29293345

RESUMO

We use a scanning nanometer-scale superconducting quantum interference device to map the stray magnetic field produced by individual ferromagnetic nanotubes (FNTs) as a function of applied magnetic field. The images are taken as each FNT is led through magnetic reversal and are compared with micromagnetic simulations, which correspond to specific magnetization configurations. In magnetic fields applied perpendicular to the FNT long axis, their magnetization appears to reverse through vortex states, that is, configurations with vortex end domains or in the case of a sufficiently short FNT with a single global vortex. Geometrical imperfections in the samples and the resulting distortion of idealized magnetization configurations influence the measured stray-field patterns.

9.
Reproduction ; 155(2): 129-139, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29101268

RESUMO

PACAP is a neuropeptide with diverse functions in various organs, including reproductive system. It is present in the testis in high concentrations, and in addition to the stage-specific expression within the seminiferous tubules, PACAP affects spermatogenesis and the functions of Leydig and Sertoli cells. Mice lacking endogenous PACAP show reduced fertility, but the possibility of abnormalities in spermatogenic signaling has not yet been investigated. Therefore, we performed a detailed morphological analysis of spermatozoa, sperm motility and investigated signaling pathways that play a role during spermatogenesis in knockout mice. No significant alterations were found in testicular morphology or motility of sperm in homozygous and heterozygous PACAP-deficient mice in spite of the moderately increased number of severely damaged sperms. However, we found robust changes in mRNA and/or protein expression of several factors that play an important role in spermatogenesis. Protein kinase A expression was markedly reduced, while downstream phospho-ERK and p38 were elevated in knockout animals. Expression of major transcription factors, such as Sox9 and phospho-Sox9, was decreased, while that of Sox10, as a redundant factor, was increased in PACAP-deficient mice. The reduced phospho-Sox9 expression was partly due to increased expression and activity of phosphatase PP2A in knockout mice. Targets of Sox transcription factors, such as collagen type IV, were reduced in knockout mice. In summary, our results show that lack of PACAP leads to disturbed signaling in spermatogenesis, which could be a factor responsible for reduced fertility in PACAP knockout mice, and further support the role of PACAP in reproduction.


Assuntos
Biomarcadores/metabolismo , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/fisiologia , Túbulos Seminíferos/patologia , Motilidade dos Espermatozoides/fisiologia , Espermatogênese , Espermatozoides/patologia , Animais , Masculino , Camundongos , Camundongos Knockout , Proteína Fosfatase 2/metabolismo , Reprodução , Túbulos Seminíferos/metabolismo , Espermatozoides/metabolismo
10.
Nanotechnology ; 29(35): 355708, 2018 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-29882748

RESUMO

Magnetic stray fields generated by domain walls (DWs) have attracted significant attention as they might be employed for precise positioning and active control of micro- and nano-sized magnetic objects in fluids or in the field of magnonics. The presented work intends to investigate the near-field response of magnetic stray field landscapes above generic types of charged DWs as occurring in thin films with in-plane anisotropy and preferential formation of Néel type DWs when disturbed by external magnetic fields. For this purpose, artificial magnetic stripe domain patterns with three defined domain configurations, i.e. head-to-head (tail-to-tail), head-to-side, and side-by-side, were fabricated via ion bombardment induced magnetic patterning of an exchange-biased IrMn/CoFe bilayer. The magnetic stray field landscapes as well as the local magnetization reversal of the various domain configurations were analyzed in an external magnetic field by scanning magnetoresistive microscopy and compared to micromagnetic simulations.

11.
Child Care Health Dev ; 44(4): 592-598, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29574895

RESUMO

BACKGROUND: Transfer of adolescents with congenital heart disease from paediatric cardiology providers to specialized adult congenital heart disease (ACHD) care providers is becoming a standard practice. However, some paediatric cardiologists continue to provide care for their patients into adult life. Little is known about the perspectives of young adult patients who have been transferred to ACHD clinics versus those who continue to receive their cardiology care in paediatric settings. METHODS: Content and thematic analysis of structured telephone interviews with 21 young adults age 18-25 (13 transferred to ACHD clinic and 8 who had not transferred) was conducted to identify similarities and differences in patient characteristics of those in ACHD versus paediatric settings. RESULTS: There were no appreciable differences in gender, age, heart disease type, and independence between those transferred to ACHD care versus those not transferred. Participants in both groups were aware of differences between the paediatric and ACHD care settings and providers, with some favouring the familiarity offered by the paediatric setting and providers. Participants had varying views on parental involvement in their care; most of them had attended clinic appointments on their own. Those who had transferred to ACHD care acknowledged that it would take time to adjust to new relationships. Positive perspectives on actual or anticipated transfer to ACHD care included a growing sense of autonomy and responsibility, as well as access to reproductive information relevant to ACHD patients. CONCLUSIONS: The absence of patient characteristics distinguishing those in ACHD care versus those still followed in paediatric care suggests that system, provider, and parent factors, rather than patient factors, may account for patients' perspectives on transfer to ACHD care.


Assuntos
Cardiologia/organização & administração , Cardiopatias Congênitas/psicologia , Cardiopatias Congênitas/terapia , Satisfação do Paciente/estatística & dados numéricos , Transição para Assistência do Adulto/organização & administração , Feminino , Seguimentos , Humanos , Masculino , Pais , Autonomia Pessoal , Adulto Jovem
12.
Phys Rev Lett ; 118(8): 087202, 2017 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-28282179

RESUMO

The internal and lattice structures of magnetic Skyrmions in B20-type FeGe are investigated using off-axis electron holography. The temperature, magnetic field, and angular dependence of the magnetic moments of individual Skyrmions are analyzed. The internal Skyrmion shape is found to vary with applied magnetic field. In contrast, the inter-Skyrmion distance remains almost unchanged in the lattice phase over the studied range of applied field. The amplitude of the local magnetic moment is found to vary with temperature, while the Skyrmion shape does not change significantly. Deviations from a circular to a hexagonal Skyrmion structure are observed in the lattice phase, in agreement with the results of micromagnetic simulations.

13.
Radiologe ; 57(8): 641-651, 2017 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-28455657

RESUMO

CLINICAL/METHODICAL ISSUE: In the treatment of the benign prostatic hyperplasia (BPH) medical and surgical therapies have been established. STANDARD RADIOLOGICAL METHODS: Prostate artery embolization (PAE) is an innovative endovascular technique that might close the gap between both these procedures. PERFORMANCE: The PAE procedure is safe and has a low incidence of side effects. The efficacy of PAE has been proven for medium sized and large sized glands as well as for intravesical protrusions. ACHIEVEMENTS: The complex mechanism of PAE carries the potential to cure lower urinary tract symptoms as well as to retard the progression of the hyperplasia. PRACTICAL RECOMMENDATIONS: Data concerning the long-term efficacy are missing at present.


Assuntos
Artérias , Embolização Terapêutica/métodos , Próstata/irrigação sanguínea , Hiperplasia Prostática/terapia , Humanos , Sintomas do Trato Urinário Inferior/terapia , Masculino , Tamanho do Órgão , Próstata/patologia , Resultado do Tratamento
14.
Acta Pharm Hung ; 87(1): 3-12, 2017.
Artigo em Inglês, Húngaro | MEDLINE | ID: mdl-29489092

RESUMO

BACKGROUND: Transdermal drug delivery is assumed to have a growing importance in drug development recently, thus it is crucial to optimize the penetration properties of drug into through the skin. Most of the current developments rely on the use of appropriate ex vivo animal or artificial models. However, the limited availability of human skin and the increasing restrictions in connection with animal testing encouraged the searchfor suitable artificial skin models. METHOD: For the review, we have searched the databases of scientific and medical research to collect the available publications about the in vitro skin models. Furthermore, we overviewed the methods of the DataBase service on ALternative Methods to animal experimentation (DB-ALM) database and the guidelines of Organisation for Economic Co-operation and Development (OECD). RESULTS: In vitro skin models have advantages like reproducibility, relatively low cost, easy storage, uncomplicated handling, and they offer a possibility for rapid screening and faster optimization of skin formulations. Furthermore, their composition can be easily modified which allows studying the relationship between certain pathological conditions and barrier function. However, the limitations of these models are needed to be taken into account. CONCLUSION: This review attempts to provide an overview of the most frequently used models, focusing on their limitations and advantages. Accessibility, easiness of the application, cost and the respective limitations have to be considered in order to choose the most appropriate in vitro model for the particular objective.


Assuntos
Fármacos Dermatológicos/administração & dosagem , Composição de Medicamentos , Administração Cutânea , Fármacos Dermatológicos/farmacocinética , Sistemas de Liberação de Medicamentos , Humanos , Técnicas In Vitro , Modelos Biológicos , Pele , Absorção Cutânea , Pele Artificial
15.
Int J Immunogenet ; 43(6): 369-375, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27774761

RESUMO

Human leucocyte antigen (HLA) genes play a central role in response to pathogens and in autoimmunity. Research to understand the effects of HLA genes on health has been limited because HLA genotyping protocols are labour intensive and expensive. Recently, algorithms to impute HLA genotype data using genome-wide association study (GWAS) data have been published. However, imputation accuracy for most of these algorithms was based primarily on training data sets of European ancestry individuals. We considered performance of two HLA-dedicated imputation algorithms - SNP2HLA and HIBAG - in a multiracial population of n = 1587 women with HLA genotyping data by gold standard methods. We first compared accuracy - defined as the percentage of correctly predicted alleles - of HLA-B and HLA-C imputation using SNP2HLA and HIBAG using a breakdown of the data set into an 80% training group and a 20% testing group. Estimates of accuracy for HIBAG were either the same or better than those for SNP2HLA. We then conducted a more thorough test of HIBAG imputation accuracy using five independent 10-fold cross-validation procedures with delineation of ancestry groups using ancestry informative markers. Overall accuracy for HIBAG was 89%. Accuracy by HLA gene was 93% for HLA-A, 84% for HLA-B, 94% for HLA-C, 83% for HLA-DQA1, 91% for HLA-DQB1 and 88% for HLA-DRB1. Accuracy was highest in the African ancestry group (the largest group) and lowest in the Hispanic group (the smallest group). Despite suboptimal imputation accuracy for some HLA gene/ancestry group combinations, the HIBAG algorithm has the advantage of providing posterior estimates of accuracy which enable the investigator to analyse subsets of the population with high predicted (e.g. >95%) imputation accuracy.


Assuntos
Antígenos HLA/genética , Antígenos HLA-A/genética , Antígenos HLA-B/genética , Antígenos HLA-C/genética , Feminino , Estudo de Associação Genômica Ampla , Genótipo , Antígenos HLA/imunologia , Antígenos HLA-A/imunologia , Antígenos HLA-B/imunologia , Antígenos HLA-C/imunologia , Haplótipos , Humanos , População Branca
16.
Int J Cosmet Sci ; 38(2): 128-38, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26084533

RESUMO

OBJECTIVES: The aim of our present work was to develop stable water-in-oil-in-water (w/o/w) cosmetic multiple emulsions that are proper for cosmetic use and can also be applied on the skin as pharmaceutical vehicles by means of Quality by Design (QbD) concept. This product design concept consists of a risk assessment step and also the 'predetermination' of the critical material attributes and process parameters of a stable multiple emulsion system. We have set up the hypothesis that the stability of multiple emulsions can be improved by the development based on such systematic planning - making a map of critical product parameters - so their industrial usage can be increased. METHODS: The risk assessment and the determination of critical physical-chemical stability parameters of w/o/w multiple emulsions to define critical control points were performed by means of quality tools and the leanqbd(™) (QbD Works LLC, Fremont, CA, U.S.A.) software. RESULTS: Critical materials and process parameters: Based on the results of preformulation experiments, three factors, namely entrapped active agent, preparation methodology and shear rate, were found to be highly critical factors for critical quality attributes (CQAs) and for stability, whereas the nature of oil was found a medium level risk factor. The results of the risk assessment are the following: (i) droplet structure and size distribution should be evaluated together to be able to predict the stability issues, (ii) the presence of entrapped active agents had a great impact on droplet structure, (iii) the viscosity curves represent the structural changes during storage, if the decrease in relative viscosity is >15% the emulsion disintegrates, and (iv) it is enough to use the shear rate between 34g and 116g relative centrifugal force (RCF). CQAs: By risk assessment, we discovered that four factors should be considered to be high-risk variables as compared to others: droplet size, droplet structure, viscosity and multiple character were found to be highly critical attributes. CONCLUSION: The preformulation experiment is the part of a development plan. On the basis of these results, the control strategy can be defined and a stable multiple emulsion can be ensured that meets the relevant stakeholders' quality expectations.


Assuntos
Cosméticos , Emulsões , Medição de Risco
17.
Neth Heart J ; 24(4): 268-74, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26924822

RESUMO

Heart failure with preserved ejection fraction, i.e. HFpEF, is highly prevalent in ageing populations, accounting for more than 50 % of all cases of heart failure in Western societies, and is closely associated with comorbidities such as obesity, diabetes and arterial hypertension. However, all large multicentre trials of potential HFpEF treatments conducted to date have failed to produce positive outcomes. These disappointing results suggest that a 'one size fits all' strategy may be ill-suited to HFpEF and support the use of tailored, personalised therapeutic approaches with specific treatments designed for specific comorbidity-related HFpEF phenotypes. The accumulation of a multitude of cardiovascular comorbidities over time leads to increased systemic inflammation, oxidative stress and coronary microvascular endothelial inflammation, eventually resulting in degradation of cyclic guanosine monophosphate (cGMP) via multiple pathways, thereby reducing protein kinase G (PKG) activity. The importance of cGMP-PKG pathway modulation is supported by growing evidence that suggests that this pathway may be a promising therapeutic target, evidence that is mainly based on its role in the phosphorylation of the giant cytoskeletal protein titin. This review will focus on the preclinical and early clinical evidence in the field of cGMP-enhancing therapies and PKG activation.

18.
Phys Rev Lett ; 115(5): 051301, 2015 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-26274409

RESUMO

We present a mass map reconstructed from weak gravitational lensing shear measurements over 139 deg2 from the Dark Energy Survey science verification data. The mass map probes both luminous and dark matter, thus providing a tool for studying cosmology. We find good agreement between the mass map and the distribution of massive galaxy clusters identified using a red-sequence cluster finder. Potential candidates for superclusters and voids are identified using these maps. We measure the cross-correlation between the mass map and a magnitude-limited foreground galaxy sample and find a detection at the 6.8σ level with 20 arc min smoothing. These measurements are consistent with simulated galaxy catalogs based on N-body simulations from a cold dark matter model with a cosmological constant. This suggests low systematics uncertainties in the map. We summarize our key findings in this Letter; the detailed methodology and tests for systematics are presented in a companion paper.

19.
Environ Toxicol ; 30(5): 501-12, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-24293352

RESUMO

A rapid cyanobacterial bloom of Cylindrospermopsis raciborskii (3.2 × 10(4) filaments/mL) was detected early November, 2012, in the Fancsika pond (East Hungary). The strong discoloration of water was accompanied by a substantial fish mortality (even dead cats were seen on the site), raising the possibility of some toxic metabolites in the water produced by the bloom-forming cyanobacteria (C. raciborskii). The potential neuronal targets of the toxic substances in the bloom sample were studied on identified neurons (RPas) in the central nervous system of Helix pomatia. The effects of the crude aqueous extracts of the Fancsika bloom sample (FBS) and the laboratory isolate of C. raciborskii from the pond (FLI) were compared with reference samples: C. raciborskii ACT 9505 (isolated in 1995 from Lake Balaton, Hungary), the cylindrospermopsin producer AQS, and the neurotoxin (anatoxin-a, homoanatoxin-a) producer Oscillatoria sp. (PCC 6506) strains. Electrophysiological tests showed that both FBS and FLI samples as well the ACT 9505 extracts modulate the acetylcholine receptors (AChRs) of the neurons, evoking ACh agonist effects, then inhibiting the ACh-evoked neuronal responses. Dose-response data suggested about the same range of toxicity of FBS and FLI samples (EC50 = 0.397 mg/mL and 0.917 mg/mL, respectively) and ACT 9505 extracts (EC50 = 0.734 mg/mL). The extract of the neurotoxin-producing PCC 6506 strain, however, proved to be the strongest inhibitor of the ACh responses on the same neurons (EC50 = 0.073 mg/mL). The presented results demonstrated an anatoxin-a-like cholinergic inhibitory effects of cyanobacterial extracts (both the environmental FBS sample, and the laboratory isolate, FLI) by some (yet unidentified) toxic components in the matrix of secondary metabolites. Previous pharmacological studies of cyanobacterial samples collected in other locations (Balaton, West Hungary) resulted in similar conclusions; therefore, we cannot exclude that this chemotype of C. raciborskii which produce anatoxin-a like neuroactive substances is more widely distributed in this region.


Assuntos
Cylindrospermopsis/metabolismo , Eutrofização , Neurotoxinas/biossíntese , Neurotoxinas/toxicidade , Uracila/análogos & derivados , Acetilcolina/metabolismo , Alcaloides , Animais , Toxinas Bacterianas/química , Toxinas Bacterianas/metabolismo , Toxinas Bacterianas/toxicidade , Compostos Bicíclicos Heterocíclicos com Pontes/química , Compostos Bicíclicos Heterocíclicos com Pontes/metabolismo , Compostos Bicíclicos Heterocíclicos com Pontes/toxicidade , Toxinas de Cianobactérias , Cylindrospermopsis/efeitos dos fármacos , Relação Dose-Resposta a Droga , Caracois Helix , Hungria , Lagos , Neurônios/efeitos dos fármacos , Oscillatoria/química , Oscillatoria/metabolismo , Receptores Colinérgicos/efeitos dos fármacos , Tropanos/química , Tropanos/metabolismo , Tropanos/toxicidade , Uracila/biossíntese , Uracila/toxicidade
20.
Appl Opt ; 53(9): 1929-37, 2014 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-24663472

RESUMO

Chromatic dispersion of a 37 cm long, solid-core photonic bandgap (PBG) fiber was studied in the wavelength range of 740-840 nm with spectral interferometry employing a Mach-Zehnder interferometer and a high resolution spectrometer. The interferometer was illuminated by a Ti:sapphire laser providing 20 fs pulses. A comparative study has been carried out to find the most accurate spectral phase retrieval method that is suitable for measuring higher order chromatic dispersion. The stationary phase point, the minima-maxima, the cosine function fit, the Fourier transform, and the windowed Fourier transform methods were tested. It was shown that out of these five techniques, the Fourier-transform method provided the dispersion coefficients with the highest accuracy, and it could also detect rapid phase changes in the vicinity of leaking mode frequencies within the transmission band of the PBG fiber.

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