Display omitted
Microfluidic devices have been widely used since 1990s for diverse manipulations of particles (a general term of beads, cells, vesicles, drops, etc.) in a variety of applications. ...Compared to the active manipulation via an externally imposed force field, the passive manipulation of particles exploits the flow-induced intrinsic lift and/or drag to control particle motion with several advantages. Along this direction, inertial microfluidics has received tremendous interest in the past decade due to its capability to handle a large volume of samples at a high throughput. This inertial lift-based approach in Newtonian fluids, however, becomes ineffective and even fails for small particles and/or at low flow rates. Recent studies have demonstrated the potential of elastic lift in non-Newtonian fluids for manipulating particles with a much smaller size and over a much wider range of flow rates. The aim of this article is to provide an overview of the various passive manipulations, including focusing, separation, washing and stretching, of particles that have thus far been demonstrated in non-Newtonian microfluidics.
Inertial microfluidics has emerged as an important tool for manipulating particles and cells. For a better design of inertial microfluidic devices, we conduct 3D direct numerical simulations (DNS) ...and experiments to determine the complicated dependence of focusing behaviour on the particle size, channel aspect ratio, and channel Reynolds number. We find that the well-known focusing of the particles at the two centers of the long channel walls occurs at a relatively low Reynolds number, whereas additional stable equilibrium positions emerge close to the short walls with increasing Reynolds number. Based on the numerically calculated trajectories of particles, we propose a two-stage particle migration which is consistent with experimental observations. We further present a general criterion to secure good focusing of particles for high flow rates. This work thus provides physical insight into the multiplex focusing of particles in rectangular microchannels with different geometries and Reynolds numbers, and paves the way for efficiently designing inertial microfluidic devices.
Exosomes, molecular cargos secreted by almost all mammalian cells, are considered as promising biomarkers to identify many diseases including cancers. However, the small size of exosomes (30–200 nm) ...poses serious challenges in their isolation from complex media containing a variety of extracellular vesicles (EVs) of different sizes, especially in small sample volumes. Here we present a viscoelasticity-based microfluidic system to directly separate exosomes from cell culture media or serum in a continuous, size-dependent, and label-free manner. Using a small amount of biocompatible polymer as the additive in the media to control the viscoelastic forces exerted on EVs, we are able to achieve a high separation purity (>90%) and recovery (>80%) of exosomes. The proposed technique may serve as a versatile platform to facilitate exosome analyses in diverse biochemical applications.
As the number of older people globally increases, health systems need to be reformed to meet the growing need for medical resources. A few previous studies reported varying health impacts of ...population ageing, but they focused only on limited countries and diseases. We comprehensively quantify the impact of population ageing on mortality for 195 countries/territories and 169 causes of death. Using data from the Global Burden of Disease Study 2017 (GBD 2017), this study derived the total number of deaths and population size for each year from 1990 to 2017. A decomposition method was used to attribute changes in total deaths to population growth, population ageing, and mortality change between 1990 and each subsequent year from 1991 through 2017, for 195 countries/territories and for countries grouped by World Bank economic development level. For countries with increases in deaths related to population ageing, we calculated the ratio of deaths attributed to mortality change to those attributed to population ageing. The proportion of people aged 65 years and older increased globally from 6.1% to 8.8%, and the number of global deaths increased by 9 million, between 1990 and 2017. Compared to 1990, 12 million additional global deaths in 2017 were associated with population ageing, corresponding to 27.9% of total global deaths. Population ageing was associated with increases in deaths in high-, upper-middle-, and lower-middle-income countries but not in low-income countries. The proportions of deaths attributed to population ageing in 195 countries/territories ranged from -43.9% to 117.4% for males and -30.1% to 153.5% for females. The 2 largest contributions of population ageing to disease-specific deaths globally between 1990 and 2017 were for ischemic heart disease (3.2 million) and stroke (2.2 million). Population ageing was related to increases in deaths in 152 countries for males and 159 countries for females, and decreases in deaths in 43 countries for males and 36 countries for females, between 1990 and 2017. The decreases in deaths attributed to mortality change from 1990 to 2017 were more than the increases in deaths related to population ageing for the whole world, as well as in 55.3% (84/152) of countries for males and 47.8% (76/159) of countries for females where population ageing was associated with increased death burden. As the GBD 2017 does not provide variances in the estimated death numbers, we were not able to quantify uncertainty in our attribution estimates. In this study, we found that population ageing was associated with substantial changes in numbers of deaths between 1990 and 2017, but the attributed proportion of deaths varied widely across country income levels, countries, and causes of death. Specific preventive and therapeutic techniques should be implemented in different countries and territories to address the growing health needs related to population ageing, especially targeting the diseases associated with the largest increase in number of deaths in the elderly.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Cell membrane coated nanoparticles (NPs) have recently been recognized as attractive nanomedical tools because of their unique properties such as immune escape, long blood circulation time, specific ...molecular recognition and cell targeting. However, the integrity of the cell membrane coating on NPs, a key metrics related to the quality of these biomimetic-systems and their resulting biomedical function, has remained largely unexplored. Here, we report a fluorescence quenching assay to probe the integrity of cell membrane coating. In contradiction to the common assumption of perfect coating, we uncover that up to 90% of the biomimetic NPs are only partially coated. Using in vitro homologous targeting studies, we demonstrate that partially coated NPs could still be internalized by the target cells. By combining molecular simulations with experimental analysis, we further identify an endocytic entry mechanism for these NPs. We unravel that NPs with a high coating degree (≥50%) enter the cells individually, whereas the NPs with a low coating degree (<50%) need to aggregate together before internalization. This quantitative method and the fundamental understanding of how cell membrane coated NPs enter the cells will enhance the rational designing of biomimetic nanosystems and pave the way for more effective cancer nanomedicine.
Viscoelasticity-induced particle migration has recently received increasing attention due to its ability to obtain high-quality focusing over a wide range of flow rates. However, its application is ...limited to low throughput regime since the particles can defocus as flow rate increases. Using an engineered carrier medium with constant and low viscosity and strong elasticity, the sample flow rates are improved to be 1 order of magnitude higher than those in existing studies. Utilizing differential focusing of particles of different sizes, here, we present sheathless particle/cell separation in simple straight microchannels that possess excellent parallelizability for further throughput enhancement. The present method can be implemented over a wide range of particle/cell sizes and flow rates. We successfully separate small particles from larger particles, MCF-7 cells from red blood cells (RBCs), and Escherichia coli (E. coli) bacteria from RBCs in different straight microchannels. The proposed method could broaden the applications of viscoelastic microfluidic devices to particle/cell separation due to the enhanced sample throughput and simple channel design.
Microfluidic techniques are effective tools for precise manipulation of particles and cells, whose enrichment and separation is crucial for a wide range of applications in biology, medicine, and ...chemistry. Recently, lateral particle migration induced by the intrinsic hydrodynamic effects in microchannels, such as inertia and elasticity, has shown its promise for high-throughput and label-free particle manipulation. The particle migration can be engineered to realize the controllable focusing and separation of particles based on a difference in size. The widespread use of inertial and viscoelastic microfluidics depends on the understanding of hydrodynamic effects on particle motion. This review will summarize the progress in the fundamental mechanisms and key applications of inertial and viscoelastic particle manipulation.
Summary Background China has experienced a remarkable epidemiological and demographic transition during the past three decades. Far less is known about this transition at the subnational level. ...Timely and accurate assessment of the provincial burden of disease is needed for evidence-based priority setting at the local level in China. Methods Following the methods of the Global Burden of Disease Study 2013 (GBD 2013), we have systematically analysed all available demographic and epidemiological data sources for China at the provincial level. We developed methods to aggregate county-level surveillance data to inform provincial-level analysis, and we used local data to develop specific garbage code redistribution procedures for China. We assessed levels of and trends in all-cause mortality, causes of death, and years of life lost (YLL) in all 33 province-level administrative units in mainland China, all of which we refer to as provinces, for the years between 1990 and 2013. Findings All provinces in mainland China have made substantial strides to improve life expectancy at birth between 1990 and 2013. Increases ranged from 4·0 years in Hebei province to 14·2 years in Tibet. Improvements in female life expectancy exceeded those in male life expectancy in all provinces except Shanghai, Macao, and Hong Kong. We saw significant heterogeneity among provinces in life expectancy at birth and probability of death at ages 0–14, 15–49, and 50–74 years. Such heterogeneity is also present in cause of death structures between sexes and provinces. From 1990 to 2013, leading causes of YLLs changed substantially. In 1990, 16 of 33 provinces had lower respiratory infections or preterm birth complications as the leading causes of YLLs. 15 provinces had cerebrovascular disease and two (Hong Kong and Macao) had ischaemic heart disease. By 2013, 27 provinces had cerebrovascular disease as the leading cause, five had ischaemic heart disease, and one had lung cancer (Hong Kong). Road injuries have become a top ten cause of death in all provinces in mainland China. The most common non-communicable diseases, including ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and cancers (liver, stomach, and lung), contributed much more to YLLs in 2013 compared with 1990. Interpretation Rapid transitions are occurring across China, but the leading health problems and the challenges imposed on the health system by epidemiological and demographic change differ between groups of Chinese provinces. Localised health policies need to be implemented to tackle the diverse challenges faced by local health-care systems. Funding China National Science & Technology Pillar Program 2013 (2013BAI04B02) and Bill & Melinda Gates Foundation.
Changes in biogeochemical cycles and the climate system due to human activities are expected to change the quantity and quality of plant litter inputs to soils. How changing quality of fresh organic ...matter (FOM) might influence the priming effect (PE) on soil organic matter (SOM) mineralization is still under debate. Here we determined the PE induced by two (13)C-labeled FOMs with contrasting nutritional quality (leaf vs. stalk of Zea mays L.). Soils from two different forest types yielded consistent results: soils amended with leaf tissue switched faster from negative PE to positive PE due to greater microbial growth compared to soils amended with stalks. However, after 16 d of incubation, soils amended with stalks had a higher PE than those amended with leaf. Phospholipid fatty acid (PLFA) results suggested that microbial demand for carbon and other nutrients was one of the major determinants of the PE observed. Therefore, consideration of both microbial demands for nutrients and FOM supply simultaneously is essential to understand the underlying mechanisms of PE. Our study provided evidence that changes in FOM quality could affect microbial utilization of substrate and PE on SOM mineralization, which may exacerbate global warming problems under future climate change.
•A novel data-driven RMPC framework for multi-zone building thermal comfort control.•A formal feasibility and stability guarantee of the proposed control framework.•A simulation case study with the ...real-world weather forecast and measure data.
This paper proposes a novel data-driven robust model predictive control (MPC) framework for a multi-zone building considering thermal comfort and uncertain weather forecast errors. The control objective is to maintain each zone's temperature and relative humidity within the specified ranges by minimizing the energy usage of the underlying heating system. A state-space model is developed to use a hybrid physics-based and data-driven method for the multi-zone building's temperature and relative humidity. The temperature and humidity RMSEs between the state-space model and the EnergyPlus-based model are less than 0.25 °C and 5.9%, respectively. The uncertainty space is based on historical weather forecast error data, which are clustered by using a k-means clustering algorithm. Machine learning approaches, including principal component analysis and kernel density estimation, are used to construct each basic uncertainty set and reduce the conservatism of resulting robust control action under disturbances. A robust MPC framework is built upon the proposed state-space model and data-driven disjunctive uncertainty set. An affine disturbance feedback rule is employed to obtain a tractable approximation of the robust MPC problem. Besides, the feasibility and stability of the proposed MPC are discussed in detail. A case study of controlling temperature and relative humidity of a multi-zone building in Ithaca, New York, USA, is presented. The results demonstrate that the proposed framework can reduce up to 8.8% of total energy consumption compared to conventional robust MPC approaches. Moreover, the proposed framework can essentially satisfy the thermal constraints that certainty equivalent MPC and robust MPC largely violate.
PDF
