| 1. |
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| 2. |
- Luo, Yifei, et al.
(författare)
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Technology Roadmap for Flexible Sensors
- 2023
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Ingår i: ACS Nano. - : American Chemical Society. - 1936-0851 .- 1936-086X. ; 17:6, s. 5211-5295
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Forskningsöversikt (refereegranskat)abstract
- Humans rely increasingly on sensors to address grand challenges and to improve quality of life in the era of digitalization and big data. For ubiquitous sensing, flexible sensors are developed to overcome the limitations of conventional rigid counterparts. Despite rapid advancement in bench-side research over the last decade, the market adoption of flexible sensors remains limited. To ease and to expedite their deployment, here, we identify bottlenecks hindering the maturation of flexible sensors and propose promising solutions. We first analyze challenges in achieving satisfactory sensing performance for real-world applications and then summarize issues in compatible sensor-biology interfaces, followed by brief discussions on powering and connecting sensor networks. Issues en route to commercialization and for sustainable growth of the sector are also analyzed, highlighting environmental concerns and emphasizing nontechnical issues such as business, regulatory, and ethical considerations. Additionally, we look at future intelligent flexible sensors. In proposing a comprehensive roadmap, we hope to steer research efforts towards common goals and to guide coordinated development strategies from disparate communities. Through such collaborative efforts, scientific breakthroughs can be made sooner and capitalized for the betterment of humanity.
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| 3. |
- Xie, Yuan, et al.
(författare)
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Wnt signaling regulates MFSD2A-dependent drug delivery through endothelial transcytosis in glioma
- 2023
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Ingår i: Neuro-Oncology. - : Oxford University Press. - 1522-8517 .- 1523-5866. ; 25:6, s. 1073-1084
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Tidskriftsartikel (refereegranskat)abstract
- Background: Systemic delivery of anti-tumor therapeutic agents to brain tumors is thwarted by the blood-brain barrier (BBB), an organotypic specialization of brain endothelial cells (ECs). A failure of pharmacological compounds to cross BBB is one culprit for the dismal prognosis of glioblastoma (GBM) patients. Identification of novel vascular targets to overcome the challenges posed by the BBB in tumors for GBM treatment is urgently needed.Methods: Temozolomide (TMZ) delivery was investigated in CT2A and PDGFB-driven RCAS/tv-a orthotopic glioma models. Transcriptome analysis was performed on ECs from murine gliomas. Mfsd2a deficient, Cav1 deficient, and Mfsd2a EC-specific inducible mice were developed to study the underlying molecular mechanisms.Results: We demonstrated that inhibiting Wnt signaling by LGK974 could increase TMZ delivery and sensitize glioma to chemotherapy in both murine glioma models. Transcriptome analysis of ECs from murine gliomas revealed that Wnt signaling inhibition enhanced vascular transcytosis as indicated by the upregulation of PLVAP and downregulation of MFSD2A. Mfsd2a deficiency in mice enhances TMZ delivery in tumors, whereas constitutive expression of Mfsd2a in ECs suppresses the enhanced TMZ delivery induced by Wnt pathway inhibition in murine glioma. In addition, Wnt signaling inhibition enhanced caveolin-1 (Cav1)-positive caveolae-mediated transcytosis in tumor ECs. Moreover, Wnt signaling inhibitor or Mfsd2a deficiency fails to enhance TMZ penetration in tumors from Cav1-deficient mice.Conclusions: These results demonstrated that Wnt signaling regulates MFSD2A-dependent TMZ delivery through a caveolae-mediated EC transcytosis pathway. Our findings identify Wnt signaling as a promising therapeutic target to improve drug delivery for GBM treatment.
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| 4. |
- Li, Shiyu, 1991-
(författare)
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Engineering Surfaces of Solid-State Nanopores for Biomolecule Sensing
- 2021
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Konstnärligt arbete (övrigt vetenskapligt/konstnärligt)abstract
- Nanopores have emerged as a special class of single-molecule analytical tool that offers immense potential for sensing and characterizing biomolecules such as nucleic acids and proteins. As an alternative to biological nanopores, solid-state nanopores present remarkable versatility due to their wide-range tunability in pore geometry and dimension as well as their excellent mechanical robustness and stability. However, being intrinsically incompatible with biomolecules, surfaces of inorganic solids need be modified to provide desired functionalities for real-life sensing purposes. In this thesis, we presented an exploration of various surface engineering strategies and an examination of several surface associated phenomena pertaining specifically to solid-state nanopores. Based on the parallel sensing concept using arrayed pores, optical readout is mainly employed throughout the whole study.For the surface engineering aspect, a list of approaches was explored. A versatile surface patterning strategy for immobilization of biomolecules was developed based on selective poly(vinylphosphonic acid) passivation and electron beam induced deposition technique. This scheme was then implemented on nanopore arrays for nanoparticle localization. In addition, vesicle rupture-based lipid bilayer coating was adapted to truncated-pyramidal nanopores, which was shown to be effective for the minimizing DNA-pore interaction. Further, HfO2 coating by means of atomic layer deposition was employed to prevent the erosion of Si-based pores and to shrink the pore diameter, which enabled reliable investigations of DNA clogging and DNA polymerase docking.For the surface associated phenomena, several findings were made. The lipid bilayer formation on truncated pyramidal nanopores via instantaneous rupture of individual vesicles was quantified based on combined ionic current monitoring and optical observation. The probability of pore clogging appeared to linearly increase with the length of DNA strands and applied bias voltage, which could be attributed a higher probability of knotting and/or folding of longer DNA strands and more frequent translocation events at higher voltage. A free-energy based analytical model was proposed to evaluate the DNA-pore interaction and to interpret observed clogging behavior. Finally, docking of DNA polymerase on nanopore arrays was demonstrated using label-free optical method based on Ca2+ indicator dyes, which may open the avenue to sequencing-by-synthesis enabled by the docked polymerase.
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| 5. |
- Mishra, A, et al.
(författare)
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Diminishing benefits of urban living for children and adolescents' growth and development
- 2023
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 615:7954, s. 874-883
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Tidskriftsartikel (refereegranskat)abstract
- Optimal growth and development in childhood and adolescence is crucial for lifelong health and well-being1–6. Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5–19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than their rural counterparts in all but a few high-income countries. By 2020, the urban height advantage became smaller in most countries, and in many high-income western countries it reversed into a small urban-based disadvantage. The exception was for boys in most countries in sub-Saharan Africa and in some countries in Oceania, south Asia and the region of central Asia, Middle East and north Africa. In these countries, successive cohorts of boys from rural places either did not gain height or possibly became shorter, and hence fell further behind their urban peers. The difference between the age-standardized mean BMI of children in urban and rural areas was <1.1 kg m–2 in the vast majority of countries. Within this small range, BMI increased slightly more in cities than in rural areas, except in south Asia, sub-Saharan Africa and some countries in central and eastern Europe. Our results show that in much of the world, the growth and developmental advantages of living in cities have diminished in the twenty-first century, whereas in much of sub-Saharan Africa they have amplified.
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| 6. |
- Sahu, Siddharth S., 1994-
(författare)
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Detection of Bio-analytes with Streaming Current : From Fundamental Principles to Novel Applications
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- A biosensor based on streaming current is a new and relatively unexplored subject with significant potential. This thesis attempts to gain a deeper understanding of the governing principles, and then exploit them to further improve its performance as well as develop novel applications. To this end, the underlying theoretical frameworks were examined and two critical parameters of the target: its size and electric charge, influencing the sensor’s sensitivity were identified. This was followed by experimental evaluation of the parameters, using a set of tailor-made proteins, aiming to understand the nature and extent of their influence on the sensor response in relation to simulation performed following an established model.The dependence of the sensor response on the charge of an analyte, or specifically the charge contrast between the sensor surface and an analyte, opens a new avenue to improve the sensitivity and also to develop novel functionality. First, this aspect was exploited to improve the sensitivity by optimizing the surface functionalization strategy. Three such methods were compared in terms of the resulting zeta potential of the surface. The sensitivity was the highest when the charge contrast was maximum. The optimal functionalization strategy was then used for highly sensitive detection of extracellular vesicles (EVs), where an improvement in the limit of detection by two orders of magnitude over the previously reported results was demonstrated. Two applications of the improved method were then demonstrated: monitoring the effectiveness of targeted cancer medicines and analysis of liquid biopsy of cancer patients via sensitive profiling of EV-membrane proteins.Improvement in the detection specificity is a critical aspect of biosensing. This was achieved by implementing a sandwich immunoassay and demonstrating the proof of concept using trastuzumab as the target and Z-domain as both the capture and detection probes. Although the improved selectivity came at the cost of a lower sensitivity, this could be mitigated via DNA-conjugation with the detection probes, a novel electrostatic labelling strategy that allows for improvement of the sensitivity by exploiting the electrostatic influence. An application of this method was then demonstrated by detecting the target from a complex medium of E. coli cell lysate. Continuing the prospect of charge engineering of antibodies, a set of positively and negatively charged antibodies were synthesized by conjugating poly-lysine and DNA oligonucleotides, respectively. This enabled stepwise, multiplexed membrane protein analysis of EVs using the alternating charge-labelled antibodies. The method was then applied to investigate EV-heterogeneity.
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| 7. |
- Hu, Qitao
(författare)
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Silicon Nanowire Based Electronic Devices for Sensing Applications
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Silicon nanowire (SiNW) based electronic devices fabricated with a complementary metal-oxide-semiconductor (CMOS) compatible process have wide-range and promising applications in sensing area. These SiNW sensors own high sensitivity, low-cost mass production possibility, and high integration density. In this thesis, we design and fabricate SiNW electronic devices with the CMOS-compatible process on silicon-on-insulator (SOI) substrates and explore their applications for ion sensing and quantum sensing. The thesis starts with ion sensing using SiNW field-effect transistors (SiNWFETs). The specific interaction between a sensing layer and analyte generates a change of local charge density and electrical potential, which can effectively modulate the conductance of SiNW channel. Multiplexed detection of molecular (MB+) and elemental (Na+) ions is demonstrated using a SiNWFET array, which is functionalized with ionophore-incorporated mixed-matrix membranes (MMMs). As a follow-up, polyethylene glycol (PEG) doping strategy is explored to suppress interference from the hydrophobic molecular ion and expand the multiplexed detection range. Then, the SiNW is downscaled to sub-10 nm with a gate-oxide-free configuration for single charge detection in liquid. We directly observe the capture and emission of a single H+ ion with individually activated Si dangling bonds (DBs) on the SiNW surface. This work demonstrates the unprecedented ability of the sub-10 nm SiNWFET for investigating the physics of the solid/liquid interface at single charge level.Apart from ion sensing, the SiNWFET can be suspended and act as a nanoelectromechanical resonator aiming for electrically detecting potential quantized mechanical vibration at low temperature. A suspended SiNW based single-hole transistor (SHT) is explored as a nanoelectromechanical resonator at 20 mK. Mechanical vibration is transduced to electrical readout by the SHT, and the transduction mechanism is dominated by piezoresistive effect. A giant effective piezoresistive gauge factor (~6000) with a strong correlation to the single-hole tunneling is also estimated. This hybrid device is demonstrated as a promising system to investigate macroscopic quantum behaviors of vibration phonon modes.Noise, including intrinsic device noise and environmental interference, is a serious concern for sensing applications of SiNW electronic devices. A H2 annealing process is explored to repair the SiNW surface defects and thus reduce the intrinsic noise by one order of magnitude. To suppress the external interference, lateral bipolar junction transistors (LBJTs) are fabricated on SOI substrate for local signal amplification of the SiNW sensors. Current gain and overall signal-to-noise ratio of the LBJTs are also optimized with an appropriate substrate voltage.
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| 8. |
- Lind, Lars, et al.
(författare)
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Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight NCD Risk Factor Collaboration (NCD-RisC)
- 2021
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Ingår i: eLife. - : eLife Sciences Publications Ltd. - 2050-084X. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- From 1985 to 2016, the prevalence of underweight decreased, and that of obesity and severe obesity increased, in most regions, with significant variation in the magnitude of these changes across regions. We investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-based studies with 187 million participants. Changes in the prevalence of underweight and total obesity, and to a lesser extent severe obesity, are largely driven by shifts in the distribution of BMI, with smaller contributions from changes in the shape of the distribution. In East and Southeast Asia and sub-Saharan Africa, the underweight tail of the BMI distribution was left behind as the distribution shifted. There is a need for policies that address all forms of malnutrition by making healthy foods accessible and affordable, while restricting unhealthy foods through fiscal and regulatory restrictions.
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| 9. |
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| 10. |
- Shi, Peng, et al.
(författare)
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Age- and gender-specific trends in respiratory outpatient visits and diagnoses at a tertiary pediatric hospital in China : a 10-year retrospective study
- 2020
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Ingår i: BMC Pediatrics. - : BioMed Central. - 1471-2431. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Respiratory infections are one of three leading causes of childhood mortality, and worldwide increase and recent plateau in childhood asthma has been reported. However, data on trends of respiratory diseases over long period of time is limited. This study aimed to determine the trends of respiratory disease outpatient visits (ROVs) and diagnoses (RODs) in one of the largest children's teaching hospitals in China between 2009 and 2018.METHODS: A retrospective study based on routine administrative data was designed and implemented according to the RECORD statement. Demographic details and diagnoses of the outpatients < 18 years visiting the respiratory department of the hospital were extracted from the Hospital Information System. Age- and gender-specific trends were illustrated by calculating average annual growth rate (AAGR) for ROVs and comparing change of proportion for different RODs over time.RESULTS: There were 698,054 ROVs from 285,574 children (40.4% female). AAGR of ROVs was 15.2%. Children aged 4 to < 7 years had a faster increase than other age groups. Bronchitis (27.6%), pneumonia (18.5%), pneumonia affecting other systems (18.4%), asthma and status asthmaticus (10.7%), and vasomotor and allergic rhinitis (9.2%) accounted for 84.4% of all RODs. The proportion of bronchitis decreased across years, with the concomitant increasing trend in the proportion of pneumonia. Age-specific trend in diagnoses showed greater proportion of asthma in all visits for the children aged 7 to < 18 years than younger children. Gender-specific trend in diagnoses showed the proportion of asthma was greater for males but the AAGR was greater for females.CONCLUSION: The persistent upward trend in ROVs was observed among children at different ages and a gender difference was also seen. In contrast to what has been reported, burden of asthma and allergies diseases continues to increase locally.
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| 11. |
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| 12. |
- Luo, Dan, et al.
(författare)
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Green, General and Low-cost Synthesis of Porous Organic Polymers in Sub-kilogram Scale for Catalysis and CO2 Capture
- 2023
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Ingår i: Angewandte Chemie International Edition. - : John Wiley & Sons. ; n/a:n/a
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Tidskriftsartikel (refereegranskat)abstract
- Porous organic polymers (POPs) with high porosity and tunable functionalities have been widely studied for use in gas separation, catalysis, energy conversion and energy storage. However, the high cost of organic monomers, and the use of toxic solvents and high temperatures during synthesis pose obstacles for large-scale production. Herein, we report the synthesis of imine and aminal-linked POPs using inexpensive diamine and dialdehyde monomer in green solvents. Theoretical calculations and control experiments show that using meta-diamines is crucial for forming aminal linkages and branching porous networks from [2 + 2] polycondensation reactions. The method demonstrates good generality in that 6 POPs were successfully synthesized from different monomers. Additionally, we scaled up the synthesis in ethanol at room temperature, resulting in the production of POPs in sub-kilogram quantities at a relatively low cost. Proof-of-concept studies demonstrate that the POPs can be used as high-performance sorbents for CO2 separation and as porous substrates for efficient heterogeneous catalysis. This method provides an environmentally friendly and cost-effective approach for large-scale synthesis of various POPs.
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| 13. |
- Taddei, C, et al.
(författare)
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Repositioning of the global epicentre of non-optimal cholesterol
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 582:7810, s. 73-
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Tidskriftsartikel (refereegranskat)abstract
- High blood cholesterol is typically considered a feature of wealthy western countries1,2. However, dietary and behavioural determinants of blood cholesterol are changing rapidly throughout the world3 and countries are using lipid-lowering medications at varying rates. These changes can have distinct effects on the levels of high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol, which have different effects on human health4,5. However, the trends of HDL and non-HDL cholesterol levels over time have not been previously reported in a global analysis. Here we pooled 1,127 population-based studies that measured blood lipids in 102.6 million individuals aged 18 years and older to estimate trends from 1980 to 2018 in mean total, non-HDL and HDL cholesterol levels for 200 countries. Globally, there was little change in total or non-HDL cholesterol from 1980 to 2018. This was a net effect of increases in low- and middle-income countries, especially in east and southeast Asia, and decreases in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe. As a result, countries with the highest level of non-HDL cholesterol—which is a marker of cardiovascular risk—changed from those in western Europe such as Belgium, Finland, Greenland, Iceland, Norway, Sweden, Switzerland and Malta in 1980 to those in Asia and the Pacific, such as Tokelau, Malaysia, The Philippines and Thailand. In 2017, high non-HDL cholesterol was responsible for an estimated 3.9 million (95% credible interval 3.7 million–4.2 million) worldwide deaths, half of which occurred in east, southeast and south Asia. The global repositioning of lipid-related risk, with non-optimal cholesterol shifting from a distinct feature of high-income countries in northwestern Europe, north America and Australasia to one that affects countries in east and southeast Asia and Oceania should motivate the use of population-based policies and personal interventions to improve nutrition and enhance access to treatment throughout the world.
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| 14. |
- Wang, Yuanbo, et al.
(författare)
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Prediction of urban airflow fields around isolated high-rise buildings using data-driven non-linear correction models
- 2023
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Ingår i: Building and Environment. - : Elsevier BV. - 0360-1323 .- 1873-684X. ; 246
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Tidskriftsartikel (refereegranskat)abstract
- When it comes to predicting urban airflow, steady Reynolds-averaged Navier-Stokes (SRANS) models that rely on Reynolds stress often face a challenge called the closure problem. This problem involves unresolved structural flaws and uncertainties in the closure coefficients used in the models. Previous attempts to recalibrate coefficients for specific urban flows without breaking the linear constitutive relation have resulted in simulation results constrained by the baseline turbulence model. Therefore, this study aims to enhance the performance of SRANS models by addressing these structural flaws. To achieve this, a novel data-driven framework is proposed. It leverages the deterministic symbolic regression algorithm to discover explicit algebraic expressions for a non-linear Reynolds stress correction model. The robustness of the correction model is ensured by maintaining the linear eddy viscosity model for iterative calculations while keeping the non-linear component frozen. The proposed framework is evaluated using three isolated building cases with varying geometric configurations and inflow boundary conditions. Findings demonstrate that computational fluid dynamics (CFD) predictions incorporating the data-driven non-linear correction model consistently align closer to wind tunnel experimental results compared to both standard and non-linear versions of the k-ε turbulence model. This improvement is reflected in reduced reattachment lengths and more accurate mean velocity distributions in the wake of buildings. However, it should be noted that there is a possibility of overpredicting wind velocity in the windward area. This study introduces valuable insights and additional strategies to enhance the prediction accuracy of SRANS models in urban airflow simulations.
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