138 research outputs found
Frisson Waves: Exploring Automatic Detection, Triggering and Sharing of Aesthetic Chills in Music Performances
Frisson is the feeling and experience of physical reactions such as shivers, tingling skin, and goosebumps. Using entrainment
through facilitating interpersonal transmissions of embodied sensations, we present "Frisson Waves" with the aim to enhance
live music performance experiences. "Frisson Waves" is an exploratory real-time system to detect, trigger and share frisson
in a wave-like pattern over audience members during music performances. The system consists of a physiological sensing
wristband for detecting frisson and a thermo-haptic neckband for inducing frisson. In a controlled environment, we evaluate
detection (n=19) and triggering of frisson (n=15). Based on our findings, we conducted an in-the-wild music concert with
48 audience members using our system to share frisson. This paper summarizes a framework for accessing, triggering and
sharing frisson. We report our research insights, lessons learned, and limitations of "Frisson Waves".
Yan He, George Chernyshov, Jiawen Han, Dingding Zheng, Ragnar Thomsen, Danny Hynds, Muyu Liu, Yuehui Yang, Yulan
Ju, Yun Suen Pai, Kouta Minamizawa, Kai Kunze, and Jamie A War
Quantitative investigation of transport and lymphatic uptake of biotherapeutics through three-dimensional physics-based computational modeling
Subcutaneous administration has become a common approach for drug delivery of biotherapeutics, such as monoclonal antibodies, which is achieved mainly by absorption through the lymphatic system. This dissertation focuses on the computational modeling of the fluid flow and solute transport in the skin tissue and the quantitative investigation of lymphatic uptake. First, the various mechanisms governing drug transport and lymphatic uptake of biotherapeutics through subcutaneous injection are investigated quantitatively through high-fidelity numerical simulations, including lymphatic drainage, blood perfusion, binding, and metabolism. The tissue is modeled as a homogeneous porous medium using both a single-layered domain and a multi-layered domain, which includes the epidermis, dermis, hypodermis (subcutaneous tissue), and muscle layers. A systematic parameter study is conducted to understand the roles of different properties of the tissue in terms of permeability, porosity, and vascular permeability. The role of binding and metabolism on drug absorption is studied by varying the binding parameters for different macromolecules after coupling the transport equation with a pharmacokinetic equation. The interstitial pressure plays an essential role in regulating the absorption of unbound drug proteins during the injection, while the binding and metabolism of drug molecules reduce the total free drugs.
The lymphatic vessel network is essential to achieve the functions of the lymphatic system. Thus, the drug transport and lymphatic uptake through a three-dimensional hybrid discrete-continuum vessel network in the skin tissue are investigated through high-fidelity numerical simulations. The explicit heterogeneous vessel network is embedded into the continuum model to investigate the role of explicit heterogeneous vessel network in drug transport and absorption. The solute transport across the vessel wall is investigated under various transport conditions. The diffusion of the drug solutes through the explicit vessel wall affects the drug absorption after the injection, while the convection under large interstitial pressure dominates the drug absorption during the injection. The effect of diffusion cannot be captured by the previously developed continuum model. Furthermore, the effects of injection volume and depth on the lymphatic uptake are investigated in a multi-layered domain. The injection volume significantly affects lymphatic uptake through the heterogeneous vessel network, while the injection depth has little influence. At last, the binding and metabolism of drug molecules are studied to bridge the simulation to the experimentally measured drug clearance.
Convective transport of drug solutes in biological tissues is regulated by the interstitial fluid pressure, which plays a crucial role in drug absorption into the lymphatic system through the subcutaneous (SC) injection. An approximate continuum poroelasticity model is developed to simulate the pressure evolution in the soft porous tissue during an SC injection. This poroelastic model mimics the deformation of the tissue by introducing the time variation of the interstitial fluid pressure. The advantage of this method lies in its computational time efficiency and simplicity, and it can accurately model the relaxation of pressure. The interstitial fluid pressure obtained using the proposed model is validated against both the analytical and the numerical solution of the poroelastic tissue model. The decreasing elasticity elongates the relaxation time of pressure, and the sensitivity of pressure relaxation to elasticity decreases with the hydraulic permeability, while the increasing porosity and permeability due to deformation alleviate the high pressure.
At last, an improved Kedem-Katchalsky model is developed to study solute transport across the lymphatic vessel network, including convection and diffusion in the multi-layered poroelastic tissue with a hybrid discrete-continuum vessel network embedded inside. The effect of different drug solutes with different Stokes radii and different structures of the lymphatic vessel network, such as fractal trees and Voronoi structure, on the lymphatic uptake is investigated. The drug solute with a small size has a larger partition coefficient and diffusivity across the openings of the lymphatic vessel wall, which favors drug absorption. The Voronoi structure is found to be more efficient in lymphatic uptake.
The systematic and quantitative investigation of subcutaneous absorption based on high-fidelity numerical simulations can provide guidance on the optimization of drug delivery systems and is valuable for the translation of bioavailability from the pre-clinical species to humans. We provide a novel approach to studying the diffusion and convection of drug molecules into the lymphatic system by developing the hybrid discrete-continuum vessel network. The study of the solute transport across the discrete lymphatic vessel walls further improves our understanding of lymphatic uptake. The novel and time-efficient computational model for solute transport across the lymphatic vasculature connects the microscopic properties of the lymphatic vessel membrane to macroscopic drug absorption. The comprehensive hybrid vessel network model developed here can be further used to improve our understanding of the diseases caused by the disturbed lymphatic system, such as lymphedema, and provide insights into the treatment of diseases caused by the malfunction of lymphatics.</p
Notice of Retraction: The Complex Effect of the Financial Crisis on U.S. S&P 500 Stock Market
Divergent Virulence Traits in Klebsiella Pneumoniae Strains of Capsular Serotype K2 and ST25: Insights from Whole-Genome Sequencing
Qingqing Du,1– 3,&ast; Fen Pan,1– 3,&ast; Fangyuan Yu,1– 3 Jie Jiang,1– 3 Chun Wang,1– 3 Huihong Qin,1– 3 Wenxin Liu,1– 3 Xiaozhou Pan,1– 3 Zhan Ma,1– 3 Wenhao Weng,1– 3 Dingding Han,1– 3 Hong Zhang1– 3 1Department of Clinical Laboratory, Shanghai Children’s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 2Institute of Pediatric Infection, Immunity, and Critical Care Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 3College of Health Science and Technology, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dingding Han, Email [email protected] Hong Zhang, Email [email protected]: Hypervirulent Klebsiella pneumoniae (hvKp) poses significant challenges for clinicians, yet the virulence determinants of hvKp have not been fully ascertained. In our study, we observed a divergence in virulence between two K2-ST25 Klebsiella pneumoniae strains, both of which carried the rmpA, iroB and peg344 virulence-associated genes. These strains exhibited different median death time (12 hour vs over one week in BALB/c) in the mice lethality assay. Whole genome sequencing (WGS) revealed that the virulence plasmids of hvKp CHK014 and non-hvKp CHK036, namely pCHK014 and pCHK036-1, shared 99.92% and 95.92% identity with the classic hypervirulent plasmid pLVPK, respectively. Additionally, in non-hvKp CHK036, the rmpA gene, along with the iro operon, iutA gene and peg344 gene, was located in the integrative and conjugative element ICEKp1 in the chromosome. However, in hvKp CHK014, the rmpA gene, peg344 gene and the iro operon were located on the IncFIB/IncHI3B virulence plasmid. Furthermore, RT-qPCR results demonstrated significantly higher expression levels of the rmpA, iroB and peg344 genes in hvKp CHK014 compared to non-hvKp CHK036. Correspondingly, the capsular polysaccharide yields regulated by the rmpA gene were significantly higher in CHK014 than CHK036. Although the copy number of rmpA gene in both strains was not altered, the poly (T) track on rmpA promoter remains as P11T, which contributed to the elevated expression level in hvKp CHK014. Whereas the poly(T) track on rmpA promoter in non-hvKp CHK036 was P10T, a shorten form of poly(T). Meanwhile, the promotor of rmpA on CHK036 included 38 additional variants, compared with CHK014 and pLVPK. These findings indicated that the expression of the rmpA gene was a crucial virulence determinant, with the P11T on promoter of rmpA gene having a higher expression potential and thus contributing to the virulence difference between hvKp CHK014 and non-hvKp CHK036 in our murine infection model.Keywords: Klebsiella pneumoniae, hypervirulence, whole-genome sequencing, gene promoto
Experimental Study on Performance of Asphalt Mixture Designed by Different Method
AbstractIn order to explore the Marshall, Superpave and GTM methods, the similarities and differences of the three design methods are detail studied. Experimental study on performance of asphalt mixture AC-13、AC-20 and AC-25 designed by different method were executed in this paper. Test results show that, GTM method gives lower void and lower bitumen aggregate ratio than other two methods, it have very better water stability and high-temperature stability. The DS value is 3256 / mm by GTM design method, is 1.91 times of the Marshall and 1.33 times of the Superpave. Superpave method gives lower bitumen aggregate ratio than Marshall method. The asphalt mixture designed by Superpave method has longer fatigue life than the mixture designed by other two methods. The volume parameters of asphalt mixture designed by Marshall can conform specification very well, but the performance of asphalt mixture seems to be worse than other two methods
The Influence of Boundary-Spanning Search on Organizational Ambidexterity Capacity: An Empirical Research in the Chinese Context
Evaluation of MMP2 as a candidate gene for high myopia
Purpose: Matrix metalloproteinase 2 (MMP2) has been shown to be expressed in the human sclera, and is increased in the sclera of the eye with myopia induced by form deprivation in chicks when compared with the control eye. The purpose of this study was to examine the relationship between high myopia and MMP2 in a mainland Han Chinese population. Methods: Four hundred unrelated patients with high myopia and 400 normal controls in a mainland Han Chinese population were studied. All the subjects were genotyped for 20 tag single nucleotide polymorphisms (SNPs) in MMP2 with the dye terminator-based SNaPshot method. The distribution of the genotypes in the cases and controls was compared with chi(2) test. Screening for mutations in the coding regions and the adjacent intronic regions of MMP2 was performed in 200 patients with high myopia and 200 normal controls by direct sequencing. Results: None of the 20 tested SNPs showed significant association with high myopia in this study. Seven variations were detected upon sequencing of the coding regions and the adjacent intronic regions of MMP2 in 200 subjects with high myopia and 200 normal controls. One novel variation, c.1287G>A (p.K429K), was detected in 79 of the 200 patients with high myopia (65 heterozygous and 14 homozygous) and in 84 of the 200 controls (67 heterozygous and 17 homozygous). The c.1810G>A mutation (p. Arg500His) was detected in three of the 200 patients with high myopia but not in the controls. The five other variations, known as polymorphisms, were detected in the case and control groups. Conclusions: We found no evidence that MMP2 is responsible for high myopia in these Han Chinese subjects and hence is unlikely to be important in the genetic predisposition to high myopia. Our results imply that MMP2 may not play a major role in high myopia in the Han Chinese population
Silk Road Fashion, China. The City and a Gate, the Pass and a Road – Four components that make Luoyang the capital of the Silk Roads between 1st and 7th century AD. The year 2018
Im Fokus unserer Forschungen zur Geschichte der alten Seidenstraßen standen vier Fundplätze innerhalb und im Umkreis der zentralchinesischen Stadt Luoyang: (1) die Paläste, Tempel und internationalen Märkte der Stadt Luoyang aus der Zeit der Östlichen Han- bis Nördlichen Wei-Dynastie (1.–6. Jh.) , (2) das Dingding-Stadttor aus der Sui- und Tang-Dynastie (gebaut 605), (3) das bisher einzige physisch erhaltene Straßensegment, der sog. Shihao-Abschnitt der alten Xiaohan-Route, und (4) die als Hangu-Pass bekannte Han-zeitliche Befestigungsanlage und Karawanserei Hangu-Pass (114 v. Chr. – 240 n. Chr.). Für das Funktionieren des überregionalen Seidenstraßenhandels hatten diese vier Orte eine Schlüsselbedeutung und belegen den Status des alten Luoyang als östlichsten Knotenpunkt des weitreichenden Handelsnetzwerks. Alle vier Fundplätze wurden national als große archäologische Entdeckungen Chinas und international mit dem Siegel des UNESCO-Weltkulturerbes ausgezeichnet. Durch den Bau von modernen Fundplatzmuseen sollen ihre Geschichten national und international verbreitet werden. Vor allem aber will man die heutige Stadt Luoyang als Industrie- und Handelszentrum dadurch stärken, dass man an ihre Blüte in historischen Zeiten erinnert. Wagenspuren und Fußabdrücke von Händlern und ihren Lastentieren lassen Erinnerungen an geschäftiges Treiben wieder aufleben. Im Wettbewerb mit der Stadt Xi’an (einst Chang’an) um den Status als „wahren“ östlichen Ausgangspunkt der Seidenstraßen ist das besonders wichtig. Als Teil einer globalen Geschichte über internationale Beziehungen und Austausch spielen die vier Fundplätze heute politisch und wirtschaftlich als Soft-Power eine große Bedeutung für den chinesischen Staat, insbesondere innerhalb der 2013 ins Leben gerufenen Belt-und-Road-Initiative
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