572 research outputs found

    A microfluidic model of human brain (μHuB) for assessment of blood brain barrier

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    Microfluidic cellular models, commonly referred to as “organs‐on‐chips,” continue to advance the field of bioengineering via the development of accurate and higher throughput models, captivating the essence of living human organs. This class of models can mimic key in vivo features, including shear stresses and cellular architectures, in ways that cannot be realized by traditional two‐dimensional in vitro models. Despite such progress, current organ‐on‐a‐chip models are often overly complex, require highly specialized setups and equipment, and lack the ability to easily ascertain temporal and spatial differences in the transport kinetics of compounds translocating across cellular barriers. To address this challenge, we report the development of a three‐dimensional human blood brain barrier (BBB) microfluidic model (μHuB) using human cerebral microvascular endothelial cells (hCMEC/D3) and primary human astrocytes within a commercially available microfluidic platform. Within μHuB, hCMEC/D3 monolayers withstood physiologically relevant shear stresses (2.73 dyn/cm2) over a period of 24 hr and formed a complete inner lumen, resembling in vivo blood capillaries. Monolayers within μHuB expressed phenotypical tight junction markers (Claudin‐5 and ZO‐1), which increased expression after the presence of hemodynamic‐like shear stress. Negligible cell injury was observed when the monolayers were cultured statically, conditioned to shear stress, and subjected to nonfluorescent dextran (70 kDa) transport studies. μHuB experienced size‐selective permeability of 10 and 70 kDa dextrans similar to other BBB models. However, with the ability to probe temporal and spatial evolution of solute distribution, μHuBs possess the ability to capture the true variability in permeability across a cellular monolayer over time and allow for evaluation of the full breadth of permeabilities that would otherwise be lost using traditional end‐point sampling techniques. Overall, the μHuB platform provides a simplified, easy‐to‐use model to further investigate the complexities of the human BBB in real‐time and can be readily adapted to incorporate additional cell types of the neurovascular unit and beyond.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149762/1/btm210126_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149762/2/btm210126.pd

    Deformabilidad en hormigones con agregados reciclados

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    Diversos trabajos han demostrado la factibilidad de elaborar hormigones con agregados reciclados, sin embargo sobre algunos aspectos poco explorados aún existen informaciones contrapuestas. Entre ellos se destacan el comportamiento diferido del hormigón (contracción y fluencia) y la capacidad de deformación en tracción (extensibilidad). Estas propiedades afectan directamente el grado de fisuración que puede tener una estructura de hormigón, lo que adquiere una significativa relevancia en la práctica, al considerar su vida en servicio. En este trabajo se presenta un estudio de la deformabilidad de hormigones que contienen 50 o 100 % de agregado grueso obtenido a partir de la trituración de losas de pavimento. Los resultados se comparan con los de otros dos hormigones elaborados con idénticas proporciones de materiales componentes variando el tipo de agregado grueso, piedra partida granítica o piedra partida cuarcítica. Se evaluaron la resistencia a tracción, la extensibilidad en flexión bajo cargas rápidas, y la fluencia en compresión. Bajo cargas de corta duración se encontró una deformabilidad creciente en el hormigón con mayor contenido de agregados reciclados, tanto en flexotracción como en compresión; también se midieron mayores valores de contracción libre y de fluencia. A partir de los resultados surge que es posible estimar la deformabilidad del hormigón con agregados reciclados siguiendo criterios similares a los aplicados en hormigones con agregados naturales; las diferencias de deformabilidad se pueden justificar considerando la menor rigidez del agregado reciclado.Different works have demonstrated the feasibility of elaborating concrete with recycled aggregates, nevertheless there is still opposite information about some aspects that have not been widely studied. The differed behaviour (shrinkage and creep) and the deformation capacity in tension (extensibility) of concrete are among them. These properties have a direct effect over the degree of cracking that can have a concrete structure so, considering its service life, they acquire a significant relevance in practice. This paper presents a study on the deformability of concretes that contain 50 or 100 % of coarse aggregate obtained from crushed pavement slabs. The results are compared with those obtained on other two concretes prepared with the same mixture proportions varying only the type of coarse aggregate, granitic crushed stone or quartzitic crushed stone. The tensile strength, extensibility in flexure under rapid rate of loading and creep in compression were evaluated. It was found that under short term loads the deformability of concrete increases with the content of recycled aggregates, both in flexure and in compression, grater values of free shrinkage and creep were also measured. From the obtained results it appears that the deformability of concrete with recycled aggregates can be estimated following the same criteria applied to concrete with natural aggregate, the differences in deformability can be justified considering the lower stiffness of the recycled aggregate

    Benefit finding in renal transplantation and its association with psychological and clinical correlates:A prospective study

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    OBJECTIVES: The identification of positive psychological changes, including benefit finding (BF), in chronic illness has gained substantial interest. However, less is known about BF in the context of a positive medical intervention. End-stage renal disease (ESRD) can be regarded as a burdensome condition, but transplantation is expected to restore physical and psychological functioning to a large extent after a period of illness. The aim of this study was to examine (1) changes in BF from pre- to 12 months post-transplantation, (2) the concurrent association of disease-related characteristics and optimism to BF, and (3) the potential causal relations between BF and distress. METHODS: In this longitudinal study, 319 patients completed questionnaires before, 3 months, 6 months, and/or 12 months post-transplantation. Multilevel models were used for the analyses. Measures included the Illness Cognitions Questionnaire to measure BF, the Life Orientation Test to measure optimism, and the General Health Questionnaire to measure distress. RESULTS: Benefit finding increased from pre- to post-transplantation. Fewer symptoms and comorbidities, and more optimism, were related to more BF over all time-points. The direction of the relation between BF and distress changed over time. Before transplantation, distress predicted an increase in BF, whereas post-transplantation, distress predicted a decrease in BF. The causal relation between BF and distress post-transplantation appeared to be reciprocal. CONCLUSIONS: A positive medical intervention such as renal transplantation might facilitate the development of BF. This study indicates the need for longitudinal research on the relation between BF and psychological health in the face of positive events. Statement of contribution What is already known on this subject? Benefit finding refers to the identification of positive psychological changes following a negative life event. Individuals can experience benefit finding following chronic illness. The positive event of kidney transplantation is associated with improvements in patients' physical and psychological functioning. What does this study add? Benefit finding increases from pre- to post-kidney transplantation. Fewer symptoms and comorbidities, and higher optimism are related to more benefit finding. Before transplantation, distress predicts an increase in benefit finding. After transplantation, there appears to be a reciprocal relation between distress and benefit finding such that distress predicts a decrease in benefit finding and benefit finding predicts a decrease in distress

    Calculation of the relative metastabilities of proteins using the CHNOSZ software package

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    <p>Abstract</p> <p>Background</p> <p>Proteins of various compositions are required by organisms inhabiting different environments. The energetic demands for protein formation are a function of the compositions of proteins as well as geochemical variables including temperature, pressure, oxygen fugacity and pH. The purpose of this study was to explore the dependence of metastable equilibrium states of protein systems on changes in the geochemical variables.</p> <p>Results</p> <p>A software package called CHNOSZ implementing the revised Helgeson-Kirkham-Flowers (HKF) equations of state and group additivity for ionized unfolded aqueous proteins was developed. The program can be used to calculate standard molal Gibbs energies and other thermodynamic properties of reactions and to make chemical speciation and predominance diagrams that represent the metastable equilibrium distributions of proteins. The approach takes account of the chemical affinities of reactions in open systems characterized by the chemical potentials of basis species. The thermodynamic database included with the package permits application of the software to mineral and other inorganic systems as well as systems of proteins or other biomolecules.</p> <p>Conclusion</p> <p>Metastable equilibrium activity diagrams were generated for model cell-surface proteins from archaea and bacteria adapted to growth in environments that differ in temperature and chemical conditions. The predicted metastable equilibrium distributions of the proteins can be compared with the optimal growth temperatures of the organisms and with geochemical variables. The results suggest that a thermodynamic assessment of protein metastability may be useful for integrating bio- and geochemical observations.</p

    Modification of COMT-dependent pain sensitivity by psychological stress and sex

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    Catecholamine-O-methyltransferase (COMT) is a polymorphic gene whose variants affect enzymatic activity and pain sensitivity via adrenergic pathways. Although COMT represents one of the most studied genes in human pain genetics, findings regarding its association with pain phenotypes are not always replicated. Here, we investigated if interactions among functional COMT haplotypes, stress, and sex can modify the effect of COMT genetic variants on pain sensitivity. We tested these interactions in a cross-sectional study, including 2 cohorts, one of 2972 subjects tested for thermal pain sensitivity (Orofacial Pain: Prospective Evaluation and Risk Assessment) and one of 948 subjects with clinical acute pain after motor vehicle collision (post-motor vehicle collision). In both cohorts, the COMT high-pain sensitivity (HPS) haplotype showed robust interaction with stress and number of copies of the HPS haplotype was positively associated with pain sensitivity in nonstressed individuals, but not in stressed individuals. In the post-motor vehicle collision cohort, there was additional modification by sex: the HPS-stress interaction was apparent in males, but not in females. In summary, our findings indicate that stress and sex should be evaluated in association studies aiming to investigate the effect of COMT genetic variants on pain sensitivity

    Interplay between elastic instabilities and shear-banding: three categories of Taylor–Couette flows and beyond

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    In the past twenty years, shear-banding flows have been probed by various techniques, such as rheometry, velocimetry and flow birefringence. In micellar solutions, many of the data collected exhibit unexplained spatiotemporal fluctuations. Recently, it has been suggested that those fluctuations originate from a purely elastic instability of the shear-banding flow. In cylindrical Couette geometry, the instability is reminiscent of the Taylor-like instability observed in viscoelastic polymer solutions. The criterion for purely elastic Taylor–Couette instability adapted to shear-banding flows suggested three categories of shear-banding depending on their stability. In the present study, we report on a large set of experimental data which demonstrates the existence of the three categories of shear-banding flows in various surfactant solutions. Consistent with theoretical predictions, increases in the surfactant concentration or in the curvature of the geometry destabilize the flow, whereas an increase in temperature stabilizes the flow. However, experiments also exhibit some interesting behaviors going beyond the purely elastic instability criterion.National Science Foundation (U.S.). Graduate Research Fellowship Progra
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