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1.
PLoS Comput Biol ; 20(4): e1012000, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38640119

RESUMO

Trial-averaged metrics, e.g. tuning curves or population response vectors, are a ubiquitous way of characterizing neuronal activity. But how relevant are such trial-averaged responses to neuronal computation itself? Here we present a simple test to estimate whether average responses reflect aspects of neuronal activity that contribute to neuronal processing. The test probes two assumptions implicitly made whenever average metrics are treated as meaningful representations of neuronal activity: Reliability: Neuronal responses repeat consistently enough across trials that they convey a recognizable reflection of the average response to downstream regions.Behavioural relevance: If a single-trial response is more similar to the average template, it is more likely to evoke correct behavioural responses. We apply this test to two data sets: (1) Two-photon recordings in primary somatosensory cortices (S1 and S2) of mice trained to detect optogenetic stimulation in S1; and (2) Electrophysiological recordings from 71 brain areas in mice performing a contrast discrimination task. Under the highly controlled settings of Data set 1, both assumptions were largely fulfilled. In contrast, the less restrictive paradigm of Data set 2 met neither assumption. Simulations predict that the larger diversity of neuronal response preferences, rather than higher cross-trial reliability, drives the better performance of Data set 1. We conclude that when behaviour is less tightly restricted, average responses do not seem particularly relevant to neuronal computation, potentially because information is encoded more dynamically. Most importantly, we encourage researchers to apply this simple test of computational relevance whenever using trial-averaged neuronal metrics, in order to gauge how representative cross-trial averages are in a given context.


Assuntos
Neurônios , Neurociências , Córtex Somatossensorial , Animais , Camundongos , Neurociências/métodos , Neurônios/fisiologia , Córtex Somatossensorial/fisiologia , Modelos Neurológicos , Optogenética/métodos , Biologia Computacional/métodos , Reprodutibilidade dos Testes , Simulação por Computador
2.
Blood ; 143(1): 79-91, 2024 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-37801721

RESUMO

ABSTRACT: Transfusion-related acute lung injury (TRALI) is one of the leading causes of transfusion-related fatalities and, to date, is without available therapies. Here, we investigated the role of the complement system in TRALI. Murine anti-major histocompatibility complex class I antibodies were used in TRALI mouse models, in combination with analyses of plasma samples from patients with TRALI. We found that in vitro complement activation was related to in vivo antibody-mediated TRALI induction, which was correlated with increased macrophage trafficking from the lungs to the blood in a fragment crystallizable region (Fc)-dependent manner and that this was dependent on C5. Human immunoglobulin G 1 variants of the murine TRALI-inducing antibody 34-1-2S, either unable to activate complement and/or bind to Fcγ receptors (FcγRs), revealed an essential role for the complement system, but not for FcγRs, in the onset of 34-1-2S-mediated TRALI in mice. In addition, we found high levels of complement activation in the plasma of patients with TRALI (n = 53), which correlated with elevated neutrophil extracellular trap (NET) markers. In vitro we found that NETs could be formed in a murine, 2-hit model, mimicking TRALI with lipopolysaccharide and C5a stimulation. Collectively, this reveals a critical role of Fc-mediated complement activation in TRALI, with a direct relation to macrophage trafficking from the lungs to the blood and an association with NET formation, suggesting that targeting the complement system may be an attractive therapeutic approach for combating TRALI.


Assuntos
Armadilhas Extracelulares , Lesão Pulmonar Aguda Relacionada à Transfusão , Humanos , Camundongos , Animais , Pulmão , Anticorpos , Macrófagos , Ativação do Complemento , Proteínas do Sistema Complemento
3.
Nat Neurosci ; 26(9): 1584-1594, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37640911

RESUMO

Brains are composed of anatomically and functionally distinct regions performing specialized tasks, but regions do not operate in isolation. Orchestration of complex behaviors requires communication between brain regions, but how neural dynamics are organized to facilitate reliable transmission is not well understood. Here we studied this process directly by generating neural activity that propagates between brain regions and drives behavior, assessing how neural populations in sensory cortex cooperate to transmit information. We achieved this by imaging two densely interconnected regions-the primary and secondary somatosensory cortex (S1 and S2)-in mice while performing two-photon photostimulation of S1 neurons and assigning behavioral salience to the photostimulation. We found that the probability of perception is determined not only by the strength of the photostimulation but also by the variability of S1 neural activity. Therefore, maximizing the signal-to-noise ratio of the stimulus representation in cortex relative to the noise or variability is critical to facilitate activity propagation and perception.


Assuntos
Encéfalo , Neurônios , Animais , Camundongos , Lobo Parietal , Fótons , Percepção
4.
Plant Physiol ; 192(2): 1234-1253, 2023 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-36943765

RESUMO

Mesophyll conductance to CO2 from the intercellular air space to the CO2-H2O exchange site has been estimated using δ18O measurements (gm18). However, the gm18 estimates are affected by the uncertainties in the δ18O of leaf water where the CO2-H2O exchange takes place and the degree of equilibration between CO2 and H2O. We show that measurements of Δ17O (i.e.Δ17O=δ17O-0.528×δ18O) can provide independent constraints on gm (gmΔ17) and that these gm estimates are less affected by fractionation processes during gas exchange. The gm calculations are applied to combined measurements of δ18O and Δ17O, and gas exchange in two C3 species, sunflower (Helianthus annuus L. cv. 'sunny') and ivy (Hedera hibernica L.), and the C4 species maize (Zea mays). The gm18 and gmΔ17 estimates agree within the combined errors (P-value, 0.876). Both approaches are associated with large errors when the isotopic composition in the intercellular air space becomes close to the CO2-H2O exchange site. Although variations in Δ17O are low, it can be measured with much higher precision compared with δ18O. Measuring gmΔ17 has a few advantages compared with gm18: (i) it is less sensitive to uncertainty in the isotopic composition of leaf water at the isotope exchange site and (ii) the relative change in the gm due to an assumed error in the equilibration fraction θeq is lower for gmΔ17 compared with gm18. Thus, using Δ17O can complement and improve the gm estimates in settings where the δ18O of leaf water varies strongly, affecting the δ18O (CO2) difference between the intercellular air space and the CO2-H2O exchange site.


Assuntos
Dióxido de Carbono , Células do Mesofilo , Folhas de Planta , Zea mays , Água , Fotossíntese
5.
Elife ; 122023 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-36648065

RESUMO

Patterns of endogenous activity in the brain reflect a stochastic exploration of the neuronal state space that is constrained by the underlying assembly organization of neurons. Yet, it remains to be shown that this interplay between neurons and their assembly dynamics indeed suffices to generate whole-brain data statistics. Here, we recorded the activity from ∼40,000 neurons simultaneously in zebrafish larvae, and show that a data-driven generative model of neuron-assembly interactions can accurately reproduce the mean activity and pairwise correlation statistics of their spontaneous activity. This model, the compositional Restricted Boltzmann Machine (cRBM), unveils ∼200 neural assemblies, which compose neurophysiological circuits and whose various combinations form successive brain states. We then performed in silico perturbation experiments to determine the interregional functional connectivity, which is conserved across individual animals and correlates well with structural connectivity. Our results showcase how cRBMs can capture the coarse-grained organization of the zebrafish brain. Notably, this generative model can readily be deployed to parse neural data obtained by other large-scale recording techniques.


Assuntos
Encéfalo , Peixe-Zebra , Animais , Encéfalo/fisiologia , Neurônios/fisiologia , Neurofisiologia , Modelos Neurológicos
6.
Circulation ; 147(13): 993-1003, 2023 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-36597865

RESUMO

BACKGROUND: Physical activity and exercise training are associated with a lower risk for coronary events. However, cross-sectional studies in middle-aged and older male athletes revealed increased coronary artery calcification (CAC) and atherosclerotic plaques, which were related to the amount and intensity of lifelong exercise. We examined the longitudinal relationship between exercise training characteristics and coronary atherosclerosis. METHODS: Middle-aged and older men from the MARC-1 (Measuring Athlete's Risk of Cardiovascular Events 1) study were invited for follow-up in MARC-2 (Measuring Athlete's Risk of Cardiovascular Events 2) study. The prevalence and severity of CAC and plaques were determined by coronary computed tomography angiography. The volume (metabolic equivalent of task [MET] hours/week) and intensity (moderate [3 to 6 MET hours/week]; vigorous [6 to 9 MET hours/week]; and very vigorous [≥9 MET hours/week]) of exercise training were quantified during follow-up. Linear and logistic regression analyses were performed to determine the association between exercise volume/intensity and markers of coronary atherosclerosis. RESULTS: We included 289 (age, 54 [50 to 60] years [median (Q1 to Q3)]) of the original 318 MARC-1 participants with a follow-up of 6.3±0.5 years (mean±SD). Participants exercised for 41 (25 to 57) MET hours/week during follow-up, of which 0% (0 to 19%) was at moderate intensity, 44% (0 to 84%) was at vigorous intensity, and 34% (0 to 80%) was at very vigorous intensity. Prevalence of CAC and the median CAC score increased from 52% to 71% and 1 (0 to 32) to 31 (0 to 132), respectively. Exercise volume during follow-up was not associated with changes in CAC or plaque. Vigorous intensity exercise (per 10% increase) was associated with a lesser increase in CAC score (ß, -0.05 [-0.09 to -0.01]; P=0.02), whereas very vigorous intensity exercise was associated with a greater increase in CAC score (ß, 0.05 [0.01 to 0.09] per 10%; P=0.01). Very vigorous exercise was also associated with increased odds of dichotomized plaque progression (adjusted odds ratio [aOR], 1.09 [1.01 to 1.18] per 10%; aOR, 2.04 [0.93 to 4.15] for highest versus lowest very vigorous intensity tertiles, respectively), and specifically with increased calcified plaques (aOR, 1.07 [1.00 to 1.15] per 10%; aOR, 2.09 [1.09 to 4.00] for highest versus lowest tertile, respectively). CONCLUSIONS: Exercise intensity but not volume was associated with progression of coronary atherosclerosis during 6-year follow-up. It is intriguing that very vigorous intensity exercise was associated with greater CAC and calcified plaque progression, whereas vigorous intensity exercise was associated with less CAC progression.


Assuntos
Doença da Artéria Coronariana , Placa Aterosclerótica , Calcificação Vascular , Pessoa de Meia-Idade , Humanos , Masculino , Idoso , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/epidemiologia , Estudos Transversais , Placa Aterosclerótica/diagnóstico por imagem , Placa Aterosclerótica/epidemiologia , Tomografia Computadorizada por Raios X , Atletas , Angiografia Coronária/métodos , Fatores de Risco , Vasos Coronários , Calcificação Vascular/epidemiologia
7.
Platelets ; 34(1): 2129604, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36185007

RESUMO

Immune-mediated platelet refractoriness (PR) remains a significant problem in the setting of platelet transfusion and is predominantly caused by the presence of alloantibodies directed against class I human leukocyte antigens (HLA). Opsonization of donor platelets with these alloantibodies can result in rapid clearance after transfusion via multiple mechanisms, including antibody dependent cellular phagocytosis (ADCP). Interestingly, not all alloimmunized patients develop PR to unmatched platelet transfusions, suggesting variation in HLA-specific IgG responses between patients. Previously, we observed that the glycosylation profile of anti-HLA antibodies was highly variable between PR patients, especially with respect to Fc galactosylation, sialylation and fucosylation. In the current study, we investigated the effect of different Fc glycosylation patterns, with known effects on complement deposition and FcγR binding, on phagocytosis of opsonized platelets by monocyte-derived human macrophages. We found that the phagocytosis of antibody- and complement-opsonized platelets, by monocyte derived M1 macrophages, was unaffected by these qualitative IgG-glycan differences.


Assuntos
Isoanticorpos , Transfusão de Plaquetas , Humanos , Plaquetas/metabolismo , Fagocitose , Macrófagos , Imunoglobulina G , Proteínas do Sistema Complemento/metabolismo , Antígenos HLA
8.
Front Immunol ; 14: 1304365, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38259472

RESUMO

Immunoglobulin G (IgG) antibodies are a critical component of the adaptive immune system, binding to and neutralizing pathogens and other foreign substances. Recent advances in molecular antibody biology and structural protein engineering enabled the modification of IgG antibodies to enhance their therapeutic potential. This review summarizes recent progress in both natural and engineered structural modifications of IgG antibodies, including allotypic variation, glycosylation, Fc engineering, and Fc gamma receptor binding optimization. We discuss the functional consequences of these modifications to highlight their potential for therapeutical applications.


Assuntos
Imunoglobulina G , Receptores de IgG , Raios gama , Glicosilação , Biologia Molecular
9.
BMJ Open ; 12(12): e065693, 2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-36456007

RESUMO

INTRODUCTION: Although recently published evidence favours transradial access (TRA) when using large-bore guiding catheters for percutaneous coronary intervention (PCI) of complex coronary lesions, the femoral artery will still be used in a considerate proportion of patients undergoing complex PCI, especially in PCI of chronic total occlusions (CTO). Ultrasound-guided puncture of the femoral artery may reduce clinically relevant access site complications, but robust evidence is lacking up to date. METHODS AND ANALYSIS: A total of 542 patients undergoing complex PCI, defined as PCI of CTO, complex bifurcation, heavy calcified lesion or left main, in which the 7-F or 8-F transfemoral access is required, will be randomised to ultrasound-guided puncture or fluoroscopy-guided puncture. The primary outcome is the incidence of the composite end-point of clinically relevant access site related bleeding and/or vascular complications requiring intervention. Access site complications and major adverse cardiovascular events up to 1 month will also be compared between both groups. ETHICS AND DISSEMINATION: Ethical approval for the study was granted by the local Ethics Committee ('Medisch Ethische Toetsing Commissie Isala Zwolle') for all Dutch sites, 'Comité Medische Ethiek Ziekenhuis Oost-Limburg' for Hospital Oost-Limburg, 'Comité d'éthique CHU-Charleroi-ISPPC' for Centre Hospilatier Universitaire de Charleroi and 'Ethik Kommission de Ärztekammer Nordrhein' for Elisabeth-Krankenhaus). The trial outcomes will be published in peer-reviewed journals of the concerned literature. The ultrasound guided transfemoral access in complex large bore PCI trial has been administered in the ClinicalTrials.gov database, reference number: NCT03846752. REGISTRATION DETAILS: ClinicalTrials.gov identifier: NCT03846752.


Assuntos
Intervenção Coronária Percutânea , Doenças Vasculares , Humanos , Punções , Artéria Femoral , Ultrassonografia de Intervenção
10.
J Thromb Haemost ; 20(12): 3011-3025, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36165642

RESUMO

BACKGROUND: The formation of alloantibodies directed against class I human leukocyte antigens (HLA) continues to be a clinically challenging complication after platelet transfusions, which can lead to platelet refractoriness (PR) and occurs in approximately 5%-15% of patients with chronic platelet support. Interestingly, anti-HLA IgG levels in alloimmunized patients do not seem to predict PR, suggesting functional or qualitative differences among anti-HLA IgG. The binding of these alloantibodies to donor platelets can result in rapid clearance after transfusion, presumably via FcγR-mediated phagocytosis and/or complement activation, which both are affected by the IgG-Fc glycosylation. OBJECTIVES: To characterize the Fc glycosylation profile of anti-HLA class I antibodies formed after platelet transfusion and to investigate its effect on clinical outcome. PATIENTS/METHODS: We screened and captured anti-HLA class I antibodies (anti-HLA A2, anti-HLA A24, and anti-HLA B7) developed after platelet transfusions in hemato-oncology patients, who were included in the PREPAReS Trial. Using liquid chromatography-mass spectrometry, we analyzed the glycosylation profiles of total and anti-HLA IgG1 developed over time. Subsequently, the glycosylation data was linked to the patients' clinical information and posttransfusion increments. RESULTS: The glycosylation profile of anti-HLA antibodies was highly variable between patients. In general, Fc galactosylation and sialylation levels were elevated compared to total plasma IgG, which correlated negatively with the platelet count increment. Furthermore, high levels of afucosylation were observed for two patients. CONCLUSIONS: These differences in composition of anti-HLA Fc-glycosylation profiles could potentially explain the variation in clinical severity between patients.


Assuntos
Isoanticorpos , Neoplasias , Humanos , Transfusão de Plaquetas , Glicosilação , Plaquetas/metabolismo , Imunoglobulina G
11.
Haematologica ; 107(10): 2432-2444, 2022 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-35354253

RESUMO

Approximately 20% of patients receiving multiple platelet transfusions develop platelet alloantibodies, which can be directed against human leukocyte antigens (HLA) and, to a lesser extent, against human platelet antigens (HPA). These antibodies can lead to the rapid clearance of donor platelets, presumably through IgG-Fc receptor (FcγR)-mediated phagocytosis or via complement activation, resulting in platelet refractoriness. Strikingly, not all patients with anti-HLA or -HPA antibodies develop platelet refractoriness upon unmatched platelet transfusions. Previously, we found that IgG Fc glycosylation of anti-HLA antibodies was highly variable between patients with platelet refractoriness, especially with respect to galactosylation and sialylation of the Fc-bound sugar moiety. Here, we produced recombinant glycoengineered anti-HLA and anti- HPA-1a monoclonal antibodies with varying Fc galactosylation and sialylation levels and studied their ability to activate the classical complement pathway. We observed that anti-HLA monoclonal antibodies with different specificities, binding simultaneously to the same HLA-molecules, or anti-HLA in combination with anti-HPA-1a monoclonal antibodies interacted synergistically with C1q, the first component of the classical pathway. Elevated Fc galactosylation and, to a lesser extent, sialylation significantly increased the complement-activating properties of anti-HLA and anti-HPA-1a monoclonal antibodies. We propose that both the breadth of the polyclonal immune response, with recognition of different HLA epitopes and in some cases HPA antigens, and the type of Fc glycosylation can provide an optimal stoichiometry for C1q binding and subsequent complement activation. These factors can shift the effect of a platelet alloimmune response to a clinically relevant response, leading to complement-mediated clearance of donor platelets, as observed in platelet refractoriness.


Assuntos
Antígenos de Plaquetas Humanas , Trombocitopenia , Anticorpos Monoclonais/farmacologia , Antígenos de Plaquetas Humanas/metabolismo , Plaquetas/metabolismo , Complemento C1q , Via Clássica do Complemento , Proteínas do Sistema Complemento/metabolismo , Epitopos , Antígenos HLA , Humanos , Imunoglobulina G/metabolismo , Isoanticorpos , Receptores de IgG/metabolismo , Açúcares/metabolismo , Trombocitopenia/metabolismo
12.
New Phytol ; 233(4): 1560-1596, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34657301

RESUMO

Generalised dose-response curves are essential to understand how plants acclimate to atmospheric CO2 . We carried out a meta-analysis of 630 experiments in which C3 plants were experimentally grown at different [CO2 ] under relatively benign conditions, and derived dose-response curves for 85 phenotypic traits. These curves were characterised by form, plasticity, consistency and reliability. Considered over a range of 200-1200 µmol mol-1 CO2 , some traits more than doubled (e.g. area-based photosynthesis; intrinsic water-use efficiency), whereas others more than halved (area-based transpiration). At current atmospheric [CO2 ], 64% of the total stimulation in biomass over the 200-1200 µmol mol-1 range has already been realised. We also mapped the trait responses of plants to [CO2 ] against those we have quantified before for light intensity. For most traits, CO2 and light responses were of similar direction. However, some traits (such as reproductive effort) only responded to light, others (such as plant height) only to [CO2 ], and some traits (such as area-based transpiration) responded in opposite directions. This synthesis provides a comprehensive picture of plant responses to [CO2 ] at different integration levels and offers the quantitative dose-response curves that can be used to improve global change simulation models.


Assuntos
Dióxido de Carbono , Folhas de Planta , Fotossíntese/fisiologia , Folhas de Planta/fisiologia , Plantas , Reprodutibilidade dos Testes
13.
J Immunol ; 207(6): 1545-1554, 2021 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-34408013

RESUMO

Human IgG contains one evolutionarily conserved N-linked glycan in its Fc region at position 297. This glycan is crucial for Fc-mediated functions, including its induction of the classical complement cascade. This is induced after target recognition through the IgG-Fab regions, allowing neighboring IgG-Fc tails to associate through Fc:Fc interaction, ultimately leading to hexamer formation. This hexamerization seems crucial for IgG to enable efficient interaction with the globular heads of the first complement component C1q and subsequent complement activation. In this study, we show that galactose incorporated in the IgG1-Fc enhances C1q binding, C4, C3 deposition, and complement-dependent cellular cytotoxicity in human erythrocytes and Raji cells. IgG1-Fc sialylation slightly enhanced binding of C1q, but had little effect on downstream complement activation. Using various mutations that decrease or increase hexamerization capacity of IgG1, we show that IgG1-Fc galactosylation has no intrinsic effect on C1q binding to IgG1, but enhances IgG1 hexamerization potential and, thereby, complement activation. These data suggest that the therapeutic potential of Abs can be amplified without introducing immunogenic mutations, by relatively simple glycoengineering.


Assuntos
Ativação do Complemento , Imunoglobulina G , Complemento C1q , Humanos , Imunoglobulina G/genética , Mutação
14.
Sci Rep ; 11(1): 14023, 2021 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-34234170

RESUMO

The clumped isotope composition (Δ47, the anomaly of the mass 47 isotopologue relative to the abundance expected from a random isotope distribution) of CO2 has been suggested as an additional tracer for gross CO2 fluxes. However, the effect of photosynthetic gas exchange on Δ47 has not been directly determined and two indirect/conceptual studies reported contradicting results. In this study, we quantify the effect of photosynthetic gas exchange on Δ47 of CO2 using leaf cuvette experiments with one C4 and two C3 plants. The experimental results are supported by calculations with a leaf cuvette model. Our results demonstrate the important roles of the Δ47 value of CO2 entering the leaf, kinetic fractionation as CO2 diffuses into, and out of the leaf and CO2-H2O isotope exchange with leaf water. We experimentally confirm the previously suggested dependence of Δ47 of CO2 in the air surrounding a leaf on the stomatal conductance and back-diffusion flux. Gas exchange can enrich or deplete the Δ47 of CO2 depending on the Δ47 of CO2 entering the leaf and the fraction of CO2 exchanged with leaf water and diffused back to the atmosphere, but under typical ambient conditions, it will lead to a decrease in Δ47.


Assuntos
Dióxido de Carbono/metabolismo , Fotossíntese , Folhas de Planta/anatomia & histologia , Folhas de Planta/fisiologia , Algoritmos , Isótopos de Carbono , Modelos Teóricos , Isótopos de Oxigênio , Fenômenos Fisiológicos Vegetais
15.
Sci Rep ; 11(1): 6423, 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33742014

RESUMO

Tailoring heat treatments for Laser Powder Bed Fusion (LPBF) processed materials is critical to ensure superior and repeatable material properties for high-end applications. This tailoring requires in-depth understanding of the LPBF-processed material. Therefore, the current study aims at unravelling the threefold interrelationship between the process (LPBF and heat treatment), the microstructure at different scales (macro-, meso-, micro-, and nano-scale), and the macroscopic material properties of AlSi10Mg. A similar solidification trajectory applies at different length scales when comparing the solidification of AlSi10Mg, ranging from mould-casting to rapid solidification (LPBF). The similarity in solidification trajectories triggers the reason why the Brody-Flemings cellular microsegregation solidification model could predict the cellular morphology of the LPBF as-printed microstructure. Where rapid solidification occurs at a much finer scale, the LPBF microstructure exhibits a significant grain refinement and a high degree of silicon (Si) supersaturation. This study has identified the grain refinement and Si supersaturation as critical assets of the as-printed microstructure, playing a vital role in achieving superior mechanical and thermal properties during heat treatment. Next, an electrical conductivity model could accurately predict the Si solute concentration in LPBF-processed and heat-treated AlSi10Mg and allows understanding the microstructural evolution during heat treatment. The LPBF-processed and heat-treated AlSi10Mg conditions (as-built (AB), direct-aged (DA), stress-relieved (SR), preheated (PH)) show an interesting range of superior mechanical properties (tensile strength: 300-450 MPa, elongation: 4-13%) compared to the mould-cast T6 reference condition.

16.
Plant Cell Environ ; 44(4): 1072-1094, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33280135

RESUMO

Plant population density is an important variable in agronomy and forestry and offers an experimental way to better understand plant-plant competition. We made a meta-analysis of responses of even-aged mono-specific stands to population density by quantifying for 3 stand and 33 individual plant variables in 334 experiments how much both plant biomass and phenotypic traits change with a doubling in density. Increasing density increases standing crop per area, but decreases the mean size of its individuals, mostly through reduced tillering and branching. Among the phenotypic traits, stem diameter is negatively affected, but plant height remains remarkably similar, partly due to an increased stem length-to-mass ratio and partly by increased allocation to stems. The reduction in biomass is caused by a lower photosynthetic rate, mainly due to shading of part of the foliage. Total seed mass per plant is also strongly reduced, marginally by lower mass per seed, but mainly because of lower seed numbers. Plants generally have fewer shoot-born roots, but their overall rooting depth seems hardly affected. The phenotypic plasticity responses to high densities correlate strongly with those to low light, and less with those to low nutrients, suggesting that at high density, shading affects plants more than nutrient depletion.


Assuntos
Plantas , Biomassa , Desenvolvimento Vegetal , Fenômenos Fisiológicos Vegetais , Plantas/metabolismo , Densidade Demográfica
17.
Blood Adv ; 4(16): 3875-3885, 2020 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-32810222

RESUMO

Transfusion-related acute lung injury (TRALI) remains a leading cause of transfusion-related deaths. In most cases, anti-leukocyte antibodies in the transfusion product trigger TRALI, but not all anti-leukocyte antibodies cause TRALI. It has been shown that the anti-major histocompatibility complex (MHC) class I antibody 34-1-2S (anti-H-2Kd) causes TRALI in BALB/c mice (MHC class I haplotype H-2Kd), whereas SF1.1.10 (anti-H-2Kd) does not. In C57BL/6 mice (MHC class I haplotype H-2Kb), TRALI only occurs when anti-MHC class I antibody AF6-88.5.5.3 (anti-H-2Kb) is administered together with a high dose of 34-1-2S. It remains unknown which specific antibody characteristics are responsible for eliciting TRALI. We therefore investigated several biological and structural features of 34-1-2S compared with other anti-MHC class I antibodies, which on their own do not cause TRALI: SF1.1.10 and AF6-88.5.5.3. No substantial differences were observed between the TRALI-causing 34-1-2S and the TRALI-resistant SF1.1.10 regarding binding affinity to H-2Kd. Regarding binding affinity to H-2Kb, only AF6-88.5.5.3 potently bound to H-2Kb, whereas 34-1-2S exhibited weak but significant cross-reactivity. Furthermore, the binding affinity to FcγRs as well as the Fc glycan composition seemed to be similar for all antibodies. Similar Fc glycosylation profiles were also observed for human TRALI-causing donor anti-HLA antibodies compared with human anti-HLA antibodies from control donors. 34-1-2S, however, displayed superior complement activation capacity, which was fully Fc dependent and not significantly dependent on Fc glycosylation. We conclude that TRALI induction is not correlated with Fab- and Fc-binding affinities for antigen and FcγRs, respectively, nor with the composition of Fc glycans; but increased Fc-mediated complement activation is correlated with TRALI induction.


Assuntos
Reação Transfusional , Lesão Pulmonar Aguda Relacionada à Transfusão , Animais , Ativação do Complemento , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL
18.
Front Plant Sci ; 10: 1016, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31440269

RESUMO

The evolution of increased competitive ability (EICA) hypothesis and the shifting defense hypothesis (SDH) predict that evolutionary changes occur in a suite of traits related to defense and growth in invasive plant species as result of the absence of specialist herbivores. We tested how this suite of traits changed due to the absence of specialist herbivores in multiple invasive regions that differ in climatic conditions with native and invasive Jacobaea vulgaris in a controlled environment. We hypothesized that invasive J. vulgaris in all invasive regions have i) a higher plant growth and underlying traits, such as photosynthetic capacity, ii) lower regrowth-related traits, such as carbohydrate storage, and iii) an increased plant qualitative defense, such as pyrrolizidine alkaloids (PAs). Our results show that invasive J. vulgaris genotypes have evolved a higher photosynthetic rate and total PA concentration but a lower investment in root carbohydrates, which supports the SDH hypothesis. All the traits changed consistently and significantly in the same direction in all four invasive regions, indicative of a parallel evolution. Climatic and soil variables did differ between ranges but explained only a very small part of the variation in trait values. The latter suggests that climate and soil changes were not the main selective forces on these traits.

19.
Adv Mater ; 31(14): e1808181, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30779385

RESUMO

Low-dimensional high-quality InSb materials are promising candidates for next-generation quantum devices due to the high carrier mobility, low effective mass, and large g-factor of the heavy element compound InSb. Various quantum phenomena are demonstrated in InSb 2D electron gases and nanowires. A combination of the best features of these two systems (pristine nanoscale and flexible design) is desirable to realize, e.g., the multiterminal topological Josephson device. Here, controlled growth of 2D nanostructures, nanoflakes, on an InSb platform is demonstrated. An assembly of nanoflakes with various dimensions and morphologies, thinner than the Bohr radius of InSb, are fabricated. Importantly, the growth of either nanowires or nanoflakes can be enforced experimentally by setting growth and substrate design parameters properly. Hall bar measurements on the nanostructures yield mobilities up to ≈20 000 cm2 V-1 s-1 and detect quantum Hall plateaus. This allows to see the system as a viable nanoscale 2D platform for future quantum devices.

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