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1.
J Cell Sci ; 137(8)2024 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-38661040

RESUMO

Expression levels of the lactate-H+ cotransporter MCT4 (also known as SLC16A3) and its chaperone CD147 (also known as basigin) are upregulated in breast cancers, correlating with decreased patient survival. Here, we test the hypothesis that MCT4 and CD147 favor breast cancer invasion through interdependent effects on extracellular matrix (ECM) degradation. MCT4 and CD147 expression and membrane localization were found to be strongly reciprocally interdependent in MDA-MB-231 breast cancer cells. Overexpression of MCT4 and/or CD147 increased, and their knockdown decreased, migration, invasion and the degradation of fluorescently labeled gelatin. Overexpression of both proteins led to increases in gelatin degradation and appearance of the matrix metalloproteinase (MMP)-generated collagen-I cleavage product reC1M, and these increases were greater than those observed upon overexpression of each protein alone, suggesting a concerted role in ECM degradation. MCT4 and CD147 colocalized with invadopodia markers at the plasma membrane. They also colocalized with MMP14 and the lysosomal marker LAMP1, as well as partially with the autophagosome marker LC3, in F-actin-decorated intracellular vesicles. We conclude that MCT4 and CD147 reciprocally regulate each other and interdependently support migration and invasiveness of MDA-MB-231 breast cancer cells. Mechanistically, this involves MCT4-CD147-dependent stimulation of ECM degradation and specifically of MMP-mediated collagen-I degradation. We suggest that the MCT4-CD147 complex is co-delivered to invadopodia with MMP14.


Assuntos
Basigina , Neoplasias da Mama , Matriz Extracelular , Proteína 1 de Membrana Associada ao Lisossomo , Metaloproteinase 14 da Matriz , Transportadores de Ácidos Monocarboxílicos , Invasividade Neoplásica , Podossomos , Feminino , Humanos , Basigina/metabolismo , Basigina/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Neoplasias da Mama/genética , Linhagem Celular Tumoral , Membrana Celular/metabolismo , Movimento Celular , Matriz Extracelular/metabolismo , Gelatina/metabolismo , Proteínas de Membrana Lisossomal/metabolismo , Proteínas de Membrana Lisossomal/genética , Metaloproteinase 14 da Matriz/metabolismo , Metaloproteinase 14 da Matriz/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Proteínas Associadas aos Microtúbulos/genética , Transportadores de Ácidos Monocarboxílicos/metabolismo , Transportadores de Ácidos Monocarboxílicos/genética , Proteínas Musculares/metabolismo , Proteínas Musculares/genética , Invasividade Neoplásica/genética , Podossomos/metabolismo
2.
Hum Mol Genet ; 32(12): 2068-2083, 2023 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-36920509

RESUMO

In humans, mutations in calmodulin cause cardiac arrhythmia. These mutations disrupt the ability of calmodulin to sense calcium concentrations and correctly regulate two central calcium channels, together obstructing heart rhythm. This correlation is well established, but also surprising since calmodulin is expressed in all tissues and interacts with hundreds of proteins. Until now, most studies have focused on cardiac cell function and regulation of specific cardiac targets, and thus, potential other effects of these mutations have largely been unexplored. Here, we introduce the nematode Caenorhabditis elegans as an in vivo model to study effects of three human calmodulin mutations with different impairment on calcium binding. We find that arrhythmic effects of the calmodulin mutations N54I and D96V can be recapitulated in disruption of two rhythmic behaviors, pharynx pumping and defecation motor program. Interestingly, we also find that these mutations affect neuronal function, but in different ways. Whereas D96V sensitizes signaling at the neuromuscular junction, N54I has a protective effect. The mutation N98S did not affect rhythmic behavior, but impaired chemosensing. Therefore, pathogenic calmodulin mutations act through different mechanisms in rhythmic behavior and neuronal function in C. elegans, emphasizing the strength of using live multicellular models. Finally, our results support the hypothesis that human calmodulin mutations could also contribute to neurological diseases.


Assuntos
Proteínas de Caenorhabditis elegans , Calmodulina , Animais , Humanos , Calmodulina/genética , Calmodulina/metabolismo , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Cálcio/metabolismo , Arritmias Cardíacas/metabolismo , Mutação , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo
3.
Plant J ; 113(2): 211-224, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36478485

RESUMO

Gravitropism guides growth to shape plant architecture above and below ground. Mutations in LAZY1 impair stem gravitropism and cause less upright inflorescence branches (wider angles). The LAZY1 protein resides at the plasma membrane and in the nucleus. The plasma membrane pool is necessary and sufficient for setting branch angles. To investigate the molecular mechanism of LAZY1 function, we screened for LAZY1-interacting proteins in yeast. We identified BRXL4, a shoot-specific protein related to BREVIS RADIX. The BRXL4-LAZY1 interaction occurred at the plasma membrane in plant cells, and not detectably in the nucleus. Mutations in the C-terminus of LAZY1, but not other conserved regions, prevented the interaction. Opposite to lazy1, brxl4 mutants displayed faster gravitropism and more upright branches. Overexpressing BRXL4 produced strong lazy1 phenotypes. The apparent negative regulation of LAZY1 function is consistent with BRXL4 reducing LAZY1 expression or the amount of LAZY1 at the plasma membrane. Measurements indicated that both are true. LAZY1 mRNA was three-fold more abundant in brxl4 mutants and almost undetectable in BRXL4 overexpressors. Plasma membrane LAZY1 was higher and nuclear LAZY1 lower in brxl4 mutants compared with the wild type. To explain these results, we suggest that BRXL4 reduces the amount of LAZY1 at the plasma membrane where it functions in gravity signaling and promotes LAZY1 accumulation in the nucleus where it reduces LAZY1 expression, possibly by suppressing its own transcription. This explanation of how BRXL4 negatively regulates LAZY1 suggests ways to modify shoot system architecture for practical purposes.


Assuntos
Arabidopsis , Gravitropismo , Gravitropismo/genética , Arabidopsis/fisiologia , Brotos de Planta/metabolismo , Ácidos Indolacéticos/metabolismo , Membrana Celular/metabolismo
4.
Nanotechnology ; 35(21)2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38382119

RESUMO

Here we report on an experimental and theoretical investigation of the long-wavelength infrared (LWIR) photoresponse of photodetectors based on arrays of three million InP nanowires with axially embedded InAsP quantum discs. An ultra-thin top indium tin oxide contact combined with a novel photogating mechanism facilitates an improved LWIR normal incidence sensitivity in contrast to traditional planar quantum well photodetectors. The electronic structure of the quantum discs, including strain and defect-induced photogating effects, and optical transition matrix elements were calculated by an 8-bandk·psimulation along with solving drift-diffusion equations to unravel the physics behind the generation of narrow linewidth intersubband signals observed from the quantum discs.

5.
J Electrocardiol ; 84: 129-136, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38663227

RESUMO

BACKGROUND: The association between type 2 diabetes and electrocardiographic (ECG) markers are incompletely explored and the dependence on diabetes duration is largely unknown. We aimed to investigate the electrocardiographic (ECG) changes associated with type 2 diabetes over time. METHODS: In this cross-sectional study, we matched people with type 2 diabetes 1:1 on sex, age, and body mass index with people without diabetes from the general population. We regressed ECG markers with the presence of diabetes and the duration of clinical diabetes, respectively, adjusted for sex, age, body mass index, smoking, heart rate, diabetes medication, renal function, hypertension, and myocardial infarction. RESULTS: We matched 988 people with type 2 diabetes (332, 34% females) with as many controls. Heart rate was 8 bpm higher (p < 0.001) in people with vs. without type 2 diabetes, but the difference declined with increasing diabetes duration. For most depolarization markers, the difference between people with and without type 2 diabetes increased progressively with diabetes duration. On average, R-wave amplitude was 6 mm lower in lead V5 (p < 0.001), P-wave duration was 5 ms shorter (p < 0.001) and QRS duration was 3 ms (p = 0.03). Among repolarization markers, T-wave amplitude (measured in V5) was lower in patients with type 2 diabetes (1 mm lower, p < 0.001) and the QRS-T angle was 10 degrees wider (p = 0.002). We observed no association between diabetes duration and repolarization markers. CONCLUSIONS: Type 2 diabetes was independently associated with electrocardiographic depolarization and repolarization changes. Differences in depolarization markers, but not repolarization markers, increased with increasing diabetes duration.


Assuntos
Diabetes Mellitus Tipo 2 , Eletrocardiografia , Humanos , Diabetes Mellitus Tipo 2/fisiopatologia , Diabetes Mellitus Tipo 2/complicações , Feminino , Masculino , Pessoa de Meia-Idade , Estudos Transversais , Idoso , Sensibilidade e Especificidade , Biomarcadores/sangue , Reprodutibilidade dos Testes , Frequência Cardíaca
6.
Chemistry ; 29(30): e202300119, 2023 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-36896735

RESUMO

Herein we report an efficient hydrosilylation strategy to selectively defunctionalize biomass-derived levulinic acid into value-added chemicals such as pentane-1,4-diol, pentan-2-ol, 2-MTHF and C5 hydrocarbons by using cost-effective silanes and the commercially available catalyst B(C6 F5 )3 at room temperature. All reactions work well in chlorinated solvents but, as a greener alternative, most reactions can be run in toluene or solvent-less.

7.
Nanotechnology ; 34(29)2023 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-37044082

RESUMO

III-V nanowire (NW) photovoltaic devices promise high efficiencies at reduced materials usage. However, research has so far focused on small devices, mostly ≤1 mm2. In this study, the upscaling potential of axial junction InP NW photovoltaic devices is investigated. Device processing was carried out on a full 2″ wafer, with device sizes up to 1 cm2, which is a significant increase from the mm-scale III-V NW photovoltaic devices published previously. The short-circuit current density of the largest 1 cm2devices, in which 460 million NWs are contacted in parallel, is on par with smaller devices. This enables a record power generation of 6.0 mW under AM1.5 G illumination, more than one order of magnitude higher than previous III-V NW photovoltaic devices. On the other hand, the fill factor of the larger devices is lower in comparison with smaller devices, which affects the device efficiency. By use of electroluminescence mapping, resistive losses in the indium tin oxide (ITO) front contact are found to limit the fill factor of the large devices. We use combined light-beam induced current (LBIC) and photoluminescence (PL) mapping as a powerful characterization tool for NW photovoltaic devices. From the LBIC and PL maps, local defects can be identified on the fully processed devices.

8.
Cardiovasc Diabetol ; 21(1): 257, 2022 11 24.
Artigo em Inglês | MEDLINE | ID: mdl-36434633

RESUMO

BACKGROUND: Subjects with Type 1 diabetes mellitus (T1DM) have an increased incidence of heart failure (HF). Several pathophysiological mechanisms have been involved in its development. The aim of this study was to analyze the potential contribution of the advanced lipoprotein profile and plasma glycosylation (GlycA) to the presence of subclinical myocardial dysfunction in subjects with T1DM. METHODS: We included subjects from a Danish cohort of T1DM subjects (Thousand & 1 study) with either diastolic and/or systolic subclinical myocardial dysfunction, and a control group without myocardial dysfunction, matched by age, sex and HbA1c. All underwent a transthoracic echocardiogram and an advanced lipoprotein profile obtained by using the NMR-based Liposcale® test. GlycA NMR signal was also analyzed. Systolic dysfunction was defined as left ventricular ejection fraction ≤ 45% and diastolic dysfunction was considered as E/e'≥12 or E/e' 8-12 + volume of the left atrium > 34 ml/m2. To identify a metabolic profile associated with the presence of subclinical myocardial dysfunction, a multivariate supervised model of classification based on least squares regression (PLS-DA regression) was performed. RESULTS: One-hundred forty-six subjects had diastolic dysfunction and 18 systolic dysfunction. Compared to the control group, patients with myocardial dysfunction had longer duration of diabetes (p = 0.005), and higher BMI (p = 0.013), serum NTproBNP concentration (p = 0.001), systolic blood pressure (p < 0.001), albuminuria (p < 0.001), and incidence of advanced retinopathy (p < 0.001). The supervised classification model identified a specific pattern associated with myocardial dysfunction, with a capacity to discriminate patients with myocardial dysfunction from controls. PLS-DA showed that triglyceride-rich lipoproteins (TGRLs), such as VLDL (total VLDL particles, large VLDL subclass and VLDL-TG content) and IDL (IDL cholesterol content), as well as the plasma concentration of GlycA, were associated with the presence of subclinical myocardial dysfunction. CONCLUSION: Proatherogenic TGRLs and the proinflammatory biomarker Glyc A are strongly associated to myocardial dysfunction in T1DM. These findings suggest a pivotal role of TGRLs and systemic inflammation in the development of subclinical myocardial dysfunction in T1DM.


Assuntos
Cardiomiopatias , Diabetes Mellitus Tipo 1 , Disfunção Ventricular Esquerda , Humanos , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/epidemiologia , Volume Sistólico/fisiologia , Função Ventricular Esquerda , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/epidemiologia , Glicosilação , Triglicerídeos , Lipoproteínas , Biomarcadores
9.
PLoS Comput Biol ; 17(9): e1009217, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34499635

RESUMO

Ergodicity describes an equivalence between the expectation value and the time average of observables. Applied to human behaviour, ergodic theories of decision-making reveal how individuals should tolerate risk in different environments. To optimize wealth over time, agents should adapt their utility function according to the dynamical setting they face. Linear utility is optimal for additive dynamics, whereas logarithmic utility is optimal for multiplicative dynamics. Whether humans approximate time optimal behavior across different dynamics is unknown. Here we compare the effects of additive versus multiplicative gamble dynamics on risky choice. We show that utility functions are modulated by gamble dynamics in ways not explained by prevailing decision theories. Instead, as predicted by time optimality, risk aversion increases under multiplicative dynamics, distributing close to the values that maximize the time average growth of in-game wealth. We suggest that our findings motivate a need for explicitly grounding theories of decision-making on ergodic considerations.


Assuntos
Tomada de Decisões , Humanos , Risco
10.
Scand Cardiovasc J ; 56(1): 256-263, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35811473

RESUMO

Aims. The European Society of Cardiology guidelines on diabetes and cardiovascular disease (CVD) recommend an electrocardiogram (ECG) in patients with diabetes and hypertension or with suspected CVD. We investigated whether ECG abnormalities can be used as a diagnostic and prognostic marker of heart failure (HF) in patients with type-2 diabetes (T2D) in secondary care diabetes-clinics. Methods. We included 722 patients with T2D in sinus rhythm. HF with preserved ejection fraction (HFpEF) was defined according to the European Society of Cardiology guidelines. Heart failure with mid-range ejection fraction (HFmrEF) was patients with dyspnoea and an LVEF 41-49%. Heart failure with reduced ejection fraction (HFrEF) or asymptomatic left ventricular systolic dysfunction (ALVSD) was defined as a LVEF ≤40%. Results. Overall, 24% patients had ECG abnormalities. A total of 15% had HF whereof 48% had ECG abnormalities. A normal ECG had a 99.3% negative predictive value (NPV) of ruling out HFrEF/ALVSD. In a sub-group with 0-1 simple clinical risk markers, the ECG ruled out both HFrEF/ALVSD, HFmrEF, and HFpEF with an NPV of 96.6%. The hazard-ratio (HR) of incident CVD or death in patients with HF and a normal ECG compared with patients without HF was 1.85 [95%CI 1.01-3.39], p = .05, while an abnormal ECG increased the HR to 3.84 [2.33-6.33], p < .001. Conclusion. HFrEF/ALVSD and HFmrEF were rare and HFpEF was frequent in this T2D population. A normal ECG ruled out HFrEF/ALVSD and in a sub-population with 0-1 simple clinical risk markers also both HFrEF/ALVSD, HFmrEF, and HFpEF.Key messagesWhat is already known about this subject?In early studies of unselected patients from primary care with suspected chronic heart failure, the presence of a normal ECG was found be useful to rule out heart failure with reduced ejection fraction.What does this study add?This study confirms that a standard electrocardiogram when normal in 722 stable outpatients with type 2 diabetes can be used to rule out HFrEF/ALVSD. Further, it adds knowledge about the risk of incident cardiovascular disease or death as a pathologic electrocardiogram increases the hazard ratio.How might this implicate clinical practice?With this study clinicians in secondary diabetes care clinics can use an electrocardiogram to select patients to undergo echocardiography when suspecting heart failure with reduced ejection fraction, as a normal electrocardiogram will rule out this diagnosis with a negative predictive value of >99%.


Assuntos
Diabetes Mellitus Tipo 2 , Insuficiência Cardíaca , Disfunção Ventricular Esquerda , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Eletrocardiografia , Humanos , Pacientes Ambulatoriais , Prognóstico , Volume Sistólico , Função Ventricular Esquerda
11.
Nano Lett ; 21(17): 7347-7353, 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34449221

RESUMO

Nanowire solar cells have the potential to reach the same efficiencies as the world-record III-V solar cells while using a fraction of the material. For solar energy harvesting, large-area nanowire solar cells have to be processed. In this work, we demonstrate the synthesis of epitaxial InP nanowire arrays on a 2 inch wafer. We define five array areas with different nanowire diameters on the same wafer. We use a photoluminescence mapper to characterize the sample optically and compare it to a homogeneously exposed reference wafer. Both steady-state and time-resolved photoluminescence maps are used to study the material's quality. From a mapping of reflectance spectra, we simultaneously extract the diameter and length of the nanowires over the full wafer. The extracted knowledge of large-scale nanowire synthesis will be crucial for the upscaling of nanowire-based solar cells, and the demonstrated wafer-scale characterization methods will be central for quality control during manufacturing.

12.
Nanotechnology ; 32(42)2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34229309

RESUMO

GaxIn(1-x)P nanowires with suitable bandgap (1.35-2.26 eV) ranging from the visible to near-infrared wavelength have great potential in optoelectronic applications. Due to the large surface-to-volume ratio of nanowires, the surface states become a pronounced factor affecting device performance. In this work, we performed a systematic study of GaxIn(1-x)P nanowires' surface passivation, utilizing AlyIn(1-y)P shells grownin situby using a metal-organic vapor phase epitaxy system. Time-resolved photoinduced luminescence and time-resolved THz spectroscopy measurements were performed to study the nanowires' carrier recombination processes. Compared to the bare Ga0.41In0.59P nanowires without shells, the hole and electron lifetime of the nanowires with the Al0.36In0.64P shells are found to be larger by 40 and 1.1 times, respectively, demonstrating effective surface passivation of trap states. When shells with higher Al composition were grown, both lifetimes of free holes and electrons decreased prominently. We attribute the acceleration of PL decay to an increase in the trap states' density due to the formation of defects, including the polycrystalline and oxidized amorphous areas in these samples. Furthermore, in a separate set of samples, we varied the shell thickness. We observed that a certain shell thickness of approximately ∼20 nm is needed for efficient passivation of Ga0.31In0.69P nanowires. The photoconductivity of the sample with a shell thickness of 23 nm decays 10 times slower compared with that of the bare core nanowires. We concluded that both the hole and electron trapping and the overall charge recombination in GaxIn(1-x)P nanowires can be substantially passivated through growing an AlyIn(1-y)P shell with appropriate Al composition and thickness. Therefore, we have developed an effectivein situsurface passivation of GaxIn(1-x)P nanowires by use of AlyIn(1-y)P shells, paving the way to high-performance GaxIn(1-x)P nanowires optoelectronic devices.

13.
Nature ; 517(7533): 191-5, 2015 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-25517098

RESUMO

Crust at many divergent plate boundaries forms primarily by the injection of vertical sheet-like dykes, some tens of kilometres long. Previous models of rifting events indicate either lateral dyke growth away from a feeding source, with propagation rates decreasing as the dyke lengthens, or magma flowing vertically into dykes from an underlying source, with the role of topography on the evolution of lateral dykes not clear. Here we show how a recent segmented dyke intrusion in the Bárðarbunga volcanic system grew laterally for more than 45 kilometres at a variable rate, with topography influencing the direction of propagation. Barriers at the ends of each segment were overcome by the build-up of pressure in the dyke end; then a new segment formed and dyke lengthening temporarily peaked. The dyke evolution, which occurred primarily over 14 days, was revealed by propagating seismicity, ground deformation mapped by Global Positioning System (GPS), interferometric analysis of satellite radar images (InSAR), and graben formation. The strike of the dyke segments varies from an initially radial direction away from the Bárðarbunga caldera, towards alignment with that expected from regional stress at the distal end. A model minimizing the combined strain and gravitational potential energy explains the propagation path. Dyke opening and seismicity focused at the most distal segment at any given time, and were simultaneous with magma source deflation and slow collapse at the Bárðarbunga caldera, accompanied by a series of magnitude M > 5 earthquakes. Dyke growth was slowed down by an effusive fissure eruption near the end of the dyke. Lateral dyke growth with segment barrier breaking by pressure build-up in the dyke distal end explains how focused upwelling of magma under central volcanoes is effectively redistributed over long distances to create new upper crust at divergent plate boundaries.

14.
Nano Lett ; 20(11): 8326-8331, 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33084341

RESUMO

Nanoscale X-ray detectors could allow higher resolution in imaging and diffraction experiments than established systems but are difficult to design due to the long absorption length of X-rays. Here, we demonstrate X-ray detection in a single nanowire in which the nanowire axis is parallel to the optical axis. In this geometry, X-ray absorption can occur along the nanowire length, while the spatial resolution is limited by the diameter. We use the device to make a high-resolution 3D image of the 88 nm diameter X-ray nanofocus at the Nanomax beamline, MAX IV synchrotron, by scanning the single pixel device in different planes along the optical axis. The images reveal fine details of the beam that are unattainable with established detectors and show good agreement with ptychography.

15.
Nano Lett ; 20(2): 887-895, 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-31891513

RESUMO

We present an in-depth analysis of the surface band alignment and local potential distribution of InP nanowires containing a p-n junction using scanning probe and photoelectron microscopy techniques. The depletion region is localized to a 15 nm thin surface region by scanning tunneling spectroscopy and an electronic shift of up to 0.5 eV between the n- and p-doped nanowire segments was observed and confirmed by Kelvin probe force microscopy. Scanning photoelectron microscopy then allowed us to measure the intrinsic chemical shift of the In 3d, In 4d, and P 2p core level spectra along the nanowire and the effect of operating the nanowire diode in forward and reverse bias on these shifts. Thanks to the high-resolution techniques utilized, we observe fluctuations in the potential and chemical energy of the surface along the nanowire in great detail, exposing the sensitive nature of nanodevices to small scale structural variations.

16.
Entropy (Basel) ; 23(12)2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34945871

RESUMO

Active Inference (AIF) is a framework that can be used both to describe information processing in naturally intelligent systems, such as the human brain, and to design synthetic intelligent systems (agents). In this paper we show that Expected Free Energy (EFE) minimisation, a core feature of the framework, does not lead to purposeful explorative behaviour in linear Gaussian dynamical systems. We provide a simple proof that, due to the specific construction used for the EFE, the terms responsible for the exploratory (epistemic) drive become constant in the case of linear Gaussian systems. This renders AIF equivalent to KL control. From a theoretical point of view this is an interesting result since it is generally assumed that EFE minimisation will always introduce an exploratory drive in AIF agents. While the full EFE objective does not lead to exploration in linear Gaussian dynamical systems, the principles of its construction can still be used to design objectives that include an epistemic drive. We provide an in-depth analysis of the mechanics behind the epistemic drive of AIF agents and show how to design objectives for linear Gaussian dynamical systems that do include an epistemic drive. Concretely, we show that focusing solely on epistemics and dispensing with goal-directed terms leads to a form of maximum entropy exploration that is heavily dependent on the type of control signals driving the system. Additive controls do not permit such exploration. From a practical point of view this is an important result since linear Gaussian dynamical systems with additive controls are an extensively used model class, encompassing for instance Linear Quadratic Gaussian controllers. On the other hand, linear Gaussian dynamical systems driven by multiplicative controls such as switching transition matrices do permit an exploratory drive.

17.
Thorax ; 75(11): 928-933, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32820080

RESUMO

INTRODUCTION: Patients with chronic obstructive pulmonary disease (COPD) are undertreated with beta-blockers following myocardial infarction (MI), possibly due to fear for acute exacerbations of COPD (AECOPD). Is beta-blocker use associated with increased risk of AECOPD in patients following first-time MI? METHODS: Danish nationwide study of patients with COPD following hospitalisation for MI from 2003 to 2015. Multivariable, time-dependent Cox regression accounting for varying beta-blocker use based on claimed prescriptions during up to 13 years of follow-up. RESULTS: A total of 10 884 patients with COPD were discharged after first-time MI. The 1-year rate of AECOPD was 35%, and 65% used beta-blockers at 1 year. Beta-blocker use was associated with a lower risk of AECOPD (multivariable-adjusted HR 0.78, 95% CI 0.74-0.83). This association was independent of the type of MI (HR 0.70, 95% CI 0.59-0.83 in ST-elevation MI (STEMI) and HR 0.80, 95% CI 0.75-0.84 in non-STEMI), presence or absence of heart failure (HR 0.82, 95% CI 0.74-0.90 and HR 0.77, 95% CI 0.72-0.82, respectively), beta-blocker dosage and type, as well as exacerbation severity. Results were similar in 1118 patients with full data on COPD severity and symptom burden (median forced expiratory volume in 1 s as percentage of predicted was 46 and majority had moderate dyspnoea), and in 1358 patients with severe COPD and frequent AECOPD with a high 1-year rate of AECOPD of 70%. DISCUSSION: Beta-blocker use was not associated with increased risk of AECOPD following MI. This finding was independent of COPD severity, symptom burden and exacerbation history, and supports the safety of beta-blockers in patients with COPD, including high-risk patients with severe disease.


Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Infarto do Miocárdio/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Dinamarca , Progressão da Doença , Feminino , Humanos , Masculino , Sistema de Registros , Fatores de Risco
18.
Cardiovasc Diabetol ; 19(1): 180, 2020 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-33066783

RESUMO

BACKGROUND: Mid-regional pro-atrial natriuretic peptide (MR-proANP) is a useful biomarker in outpatients with type 2 diabetes (T2D) to diagnose heart failure (HF). Elevated B-type natriuretic peptides are included in the definition of HF with preserved ejection fraction (HFpEF) but little is known about the prognostic value of including A-type natriuretic peptides (MR-proANP) in the evaluation of patients with T2D. METHODS: We prospectively evaluated the risk of incident cardiovascular (CV) events in outpatients with T2D (n = 806, mean ± standard deviation age 64 ± 10 years, 65% male, median [interquartile range] duration of diabetes 12 [6-17] years, 17.5% with symptomatic HFpEF) according to MR-proANP levels and stratified according to HF-status including further stratification according to a prespecified cut-off level of MR-proANP. RESULTS: A total of 126 CV events occurred (median follow-up 4.8 [4.1-5.3] years). An elevated MR-proANP, with a cut-off of 60 pmol/l or as a continuous variable, was associated with incident CV events (p < 0.001). Compared to patients without HF, patients with HFpEF and high MR-proANP (≥ 60 pmol/l; median 124 [89-202] pmol/l) and patients with HF and reduced ejection fraction (HFrEF) had a higher risk of CV events (multivariable model; hazard ratio (HR) 2.56 [95% CI 1.64-4.00] and 3.32 [1.64-6.74], respectively). Conversely, patients with HFpEF and low MR-proANP (< 60 pmol/l; median 46 [32-56] pmol/l) did not have an increased risk (HR 2.18 [0.78-6.14]). CONCLUSIONS: Patients with T2D and HFpEF with high MR-proANP levels had an increased risk for CV events compared to patients with HFpEF without elevated MR-proANP and compared to patients without HF, supporting the use of MR-proANP in the definition of HFpEF from a prognostic point-of-view.


Assuntos
Adrenomedulina/sangue , Doenças Cardiovasculares/sangue , Diabetes Mellitus Tipo 2/sangue , Insuficiência Cardíaca/sangue , Fragmentos de Peptídeos/sangue , Precursores de Proteínas/sangue , Idoso , Biomarcadores/sangue , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Dinamarca/epidemiologia , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/fisiopatologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Medição de Risco , Fatores de Risco , Volume Sistólico , Regulação para Cima , Função Ventricular Esquerda
19.
Nanotechnology ; 31(20): 204002, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32106108

RESUMO

We report on the use of a sacrificial AlAs segment to enable substrate reuse for nanowire synthesis. A silicon nitride template was deposited on a p-type GaAs substrate. Then a pattern was transferred to the substrate by nanoimprint lithography and reactive ion etching. Thermal evaporation was used to define Au seed particles. Metalorganic vapour phase epitaxy was used to grow AlAs-GaAs NWs in the vapour-liquid-solid growth mode. The yield of synthesised nanowires, compared to the number expected from the patterned template, was more than 80%. After growth, the nanowires were embedded in a polymer and mechanically removed from the parent substrate. The parent substrate was then immersed in an HCl:H2O (1:1) mixture to dissolve the remaining stub of the sacrificial AlAs segment. The pattern fidelity was preserved after peeling off the nanowires and cleaning, and the semiconductor surface was flat and ready for reuse. Au seed particles were then deposited on the substrate by use of pulse electrodeposition, which was selective to the openings in the growth template, and then nanowires were regrown. The yield of regrowth was less optimal compared to the first growth but the pattern was preserved. Our results show a promising approach to reduce the final cost of III-V nanowire based solar cells.

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