Platelet accumulation in an endothelium-coated elastic vein valve model of deep vein thrombosis is mediated by GPIbα—VWF interaction

Deep vein thrombosis is a life-threatening disease that takes millions of people's lives worldwide. Given both technical and ethical issues of using animals in research, it is necessary to develop an appropriate in vitro model that would recapitulate the conditions of venous thrombus development. We present here a novel microfluidics vein-on-a-chip with moving valve leaflets to mimic the hydrodynamics in a vein, and Human Umbilical Vein Endothelial Cell (HUVEC) monolayer. A pulsatile flow pattern, typical for veins, was used in the experiments. Unstimulated human platelets, reconstituted with the whole blood, accumulated at the luminal side of the leaflet tips proportionally to the leaflet flexibility. Platelet activation by thrombin induced robust platelet accrual at the leaflet tips. Inhibition of glycoprotein (GP) IIb-IIIa did not decrease but, paradoxically, slightly increased platelet accumulation. In contrast, blockade of the interaction between platelet GPIbα and A1 domain of von Willebrand factor completely abolished platelet deposition. Stimulation of the endothelium with histamine, a known secretagogue of Weibel-Palade bodies, promoted platelet accrual at the basal side of the leaflets, where human thrombi are usually observed. Thus, platelet deposition depends on the leaflet flexibility, and accumulation of activated platelets at the valve leaflets is mediated by GPIbα-VWF interaction

Planejamento estratégico otimizado para plantios de Eucalyptus spp.

Este trabalho teve como objetivo principal simular e avaliar, em termos de produção e rentabilidade financeira, regimes de manejo para florestas de Eucalyptus spp. Os dados utilizados nesta pesquisa foram cedidos por uma empresa localizada no noroeste do estado de São Paulo. O objeto deste estudo compreende 4.801 talhões, organizados em 280 hortos, que perfazem uma área de 88.663 hectares e abastecem duas fábricas de papel e celulose. Os dados organizados e armazenados no software Access, continham todas as informações referentes à base florestal da empresa. Os regimes de manejo foram organizados por tipo de propriedade (própria e fomento) e compreendiam dois enfoques distintos: produção de madeira exclusivamente para celulose e consórcio de madeira para celulose e serraria. Os cenários foram criados pela variação nos regimes de manejo (somente celulose ou celulose + serraria) e mudança nas restrições dos modelos, tais como: taxa de juros (8% e 12%), preço da madeira para serraria (50% e 100% maior em relação ao preço para celulose) e diferentes limites de variação da mão-de-obra (10% e 20%). Cada um dos doze cenários formulados foi submetido às funções objetivo: Maximizar VPLa (valor Presente Liquido Anualizado) e minimizar compra de madeira, sujeito a algumas combinações de restrições, a saber: somente restrições obrigatórias (tais como restrições de área dos talhões, dentre outras) e o conjunto de restrições obrigatórias, abastecimento da demanda industrial e equilíbrio da produção florestal. Pôde-se observar que a maximização do VPLa sem que sejam submetidas restrições de compra, venda e transferência e equilíbrio da produção florestal gera resultados caóticos, impossíveis de serem viabilizados na prática; Quando é dada a opção de produção de madeira para serraria, os regimes de manejo que compreendem desbastes são amplamente utilizados, especialmente quando se objetiva maximizar o VPLa ; Os regimes de manejo, a produção e as operações florestais permanecem praticamente inalterados diante da mudança de preços da madeira; A mudança de 8% para 12% na taxa de juros pode representar decréscimo de 38% no VPLa; Sendo permitida maior oscilação na produção, na maioria dos casos, o VPLa é amplificado, no entanto, esta prática gera maior irregularidade na produção, o que pode ser indesejável do ponto de vista operacional; A taxa de juros influencia no VPLa de maneira mais incisiva quando comparada à variação na margem de oscilação da produção; Cenários simulados com desbastes e produção de madeira para serraria apresentaram maiores valores de VPLa quando comparados aos de produção exclusiva de madeira para celulose

Facile tuning of the mechanical properties of a biocompatible soft material

ISSN:2045-232

Laser-inscribed contact lens sensors for the detection of analytes in the tear fluid

Tears exhibit compositional variations as a response to ocular and systemic metabolic conditions, and they can therefore be used for the assessment of physiological health. Here, microfluidic contact lenses were developed as wearable platforms for in situ tear pH, glucose, protein, and nitrite ions sensing. The microfluidic system was inscribed in commercial contact lenses by CO2 laser ablation. The microchannel consisted on a central ring with four branches, and biosensors were embedded within microcavities located at the branches ends. The device was tested with artificial tears and colorimetric readouts were performed using a smartphone-MATLAB algorithm based on the nearest neighbor model. Sensors responded within a time range of 15 s, and yielded sensitivities of 12.23 nm/pH unit, 1.4 nm/mmol L−1 of glucose, 0.49 nm/g L−1 of proteins, and 0.03 nm/μmol L−1 of nitrites. Contact lens sensing platforms may provide on-eye tears screening with applications in the monitoring of the ocular health both in clinics and at point-of-care settings

Fabrication of gradient hydrogels using a thermophoretic approach in microfluidics

The extracellular matrix presents spatially varying physical cues that can influence cell behavior in many processes. Physical gradients within hydrogels that mimic the heterogenous mechanical microenvironment are useful to study the impact of these cues on cellular responses. Therefore, simple and reliable techniques to create such gradient hydrogels are highly desirable. This work demonstrates the fabrication of stiffness gradient Gellan gum (GG) hydrogels by applying a temperature gradient across a microchannel containing hydrogel precursor solution. Thermophoretic migration of components within the precursor solution generates a concentration gradient that mirrors the temperature gradient profile, which translates into mechanical gradients upon crosslinking. Using this technique, GG hydrogels with stiffness gradients ranging from 20 to 90 kPa over 600 µm are created, covering the elastic moduli typical of moderately hard to hard tissues. MC3T3 osteoblast cells are then cultured on these gradient substrates, which exhibit preferential migration and enhanced osteogenic potential toward the stiffest region on the gradient. Overall, the thermophoretic approach provides a non-toxic and effective method to create hydrogels with defined mechanical gradients at the micron scale suitable for in vitro biological studies and potentially tissue engineering applications