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  • 3701.
    Zhao, Xin
    et al.
    Guangzhou Med Univ, Sch Pharmaceut Sci, Key Lab Mol Target & Clin Pharmacol, State Key Lab Resp Dis, Guangzhou 511436, Guangdong, Peoples R China.;Guangzhou Med Univ, Affiliated Hosp 5, Guangzhou 511436, Guangdong, Peoples R China.;Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, Guangzhou 510530, Guangdong, Peoples R China.;Univ Arizona, Coll Pharm, Dept Pharmacol & Toxicol, Tucson, AZ 85721 USA..
    Li, Runfeng
    Guangzhou Med Univ, Guangzhou Inst Resp Hlth, Affiliated Hosp 1, Natl Clin Res Ctr Resp Dis,State Key Lab Resp Dis, Guangzhou 510120, Guangdong, Peoples R China..
    Zhou, Yang
    AlbaNova Univ Ctr, Royal Inst Technol KTH, Sch Biotechnol, Div Theoret Chem & Biol, SE-10044 Stockholm, Sweden..
    Xiao, Mengjie
    Guangzhou Med Univ, Sch Pharmaceut Sci, Key Lab Mol Target & Clin Pharmacol, State Key Lab Resp Dis, Guangzhou 511436, Guangdong, Peoples R China.;Guangzhou Med Univ, Affiliated Hosp 5, Guangzhou 511436, Guangdong, Peoples R China.;Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, Guangzhou 510530, Guangdong, Peoples R China..
    Ma, Chunlong
    Univ Arizona, Coll Pharm, Dept Pharmacol & Toxicol, Tucson, AZ 85721 USA.;Univ Arizona, BIO5 Inst, Tucson, AZ 85721 USA..
    Yang, Zhongjin
    Guangzhou Med Univ, Sch Pharmaceut Sci, Key Lab Mol Target & Clin Pharmacol, State Key Lab Resp Dis, Guangzhou 511436, Guangdong, Peoples R China.;Guangzhou Med Univ, Affiliated Hosp 5, Guangzhou 511436, Guangdong, Peoples R China..
    Zeng, Shaogao
    Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, Guangzhou 510530, Guangdong, Peoples R China..
    Du, Qiuling
    Guangzhou Med Univ, Guangzhou Inst Resp Hlth, Affiliated Hosp 1, Natl Clin Res Ctr Resp Dis,State Key Lab Resp Dis, Guangzhou 510120, Guangdong, Peoples R China..
    Yang, Chunguang
    Guangzhou Med Univ, Guangzhou Inst Resp Hlth, Affiliated Hosp 1, Natl Clin Res Ctr Resp Dis,State Key Lab Resp Dis, Guangzhou 510120, Guangdong, Peoples R China..
    Jiang, Haiming
    Guangzhou Med Univ, Guangzhou Inst Resp Hlth, Affiliated Hosp 1, Natl Clin Res Ctr Resp Dis,State Key Lab Resp Dis, Guangzhou 510120, Guangdong, Peoples R China..
    Hu, Yanmei
    Univ Arizona, Coll Pharm, Dept Pharmacol & Toxicol, Tucson, AZ 85721 USA.;Univ Arizona, BIO5 Inst, Tucson, AZ 85721 USA..
    Wang, Kefeng
    Guangzhou Med Univ, Sch Pharmaceut Sci, Key Lab Mol Target & Clin Pharmacol, State Key Lab Resp Dis, Guangzhou 511436, Guangdong, Peoples R China.;Guangzhou Med Univ, Affiliated Hosp 5, Guangzhou 511436, Guangdong, Peoples R China..
    Mok, Chris Ka Pun
    Guangzhou Med Univ, Guangzhou Inst Resp Hlth, Affiliated Hosp 1, Natl Clin Res Ctr Resp Dis,State Key Lab Resp Dis, Guangzhou 510120, Guangdong, Peoples R China.;Univ Hong Kong, HKU Li Ka Shing Fac Med, Sch Publ Hlth, HKU Pasteur Res Pole, 5 Sassoon Rd, Hong Kong, Peoples R China..
    Sun, Ping
    Guangzhou Med Univ, Sch Pharmaceut Sci, Key Lab Mol Target & Clin Pharmacol, State Key Lab Resp Dis, Guangzhou 511436, Guangdong, Peoples R China.;Guangzhou Med Univ, Affiliated Hosp 5, Guangzhou 511436, Guangdong, Peoples R China..
    Dong, Jianghong
    Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, Guangzhou 510530, Guangdong, Peoples R China..
    Cui, Wei
    Wang, Jun
    Univ Arizona, Coll Pharm, Dept Pharmacol & Toxicol, Tucson, AZ 85721 USA.;Univ Arizona, BIO5 Inst, Tucson, AZ 85721 USA..
    Tu, Yaoquan
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Teoretisk kemi och biologi.
    Yang, Zifeng
    Guangzhou Med Univ, Guangzhou Inst Resp Hlth, Affiliated Hosp 1, Natl Clin Res Ctr Resp Dis,State Key Lab Resp Dis, Guangzhou 510120, Guangdong, Peoples R China..
    Hu, Wenhui
    Guangzhou Med Univ, Sch Pharmaceut Sci, Key Lab Mol Target & Clin Pharmacol, State Key Lab Resp Dis, Guangzhou 511436, Guangdong, Peoples R China.;Guangzhou Med Univ, Affiliated Hosp 5, Guangzhou 511436, Guangdong, Peoples R China.;Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, Guangzhou 510530, Guangdong, Peoples R China..
    Discovery of Highly Potent Pinanamine-Based Inhibitors against Amantadine- and Oseltamivir-Resistant Influenza A Viruses2018Inngår i: Journal of Medicinal Chemistry, ISSN 0022-2623, E-ISSN 1520-4804, Vol. 61, nr 12, s. 5187-5198Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Influenza pandemic is a constant major threat to public health caused by influenza A viruses (IAVs). IAVs are subcategorized by the surface proteins hemagglutinin (HA) and neuraminidase (NA), in which they are both essential targets for drug discovery. While it is of great concern that NA inhibitor oseltamivir resistant strains are frequently identified from human or avian influenza virus, structural and functional characterization of influenza HA has raised hopes for new antiviral therapies. In this study, we explored a structure-activity relationship (SAR) of pinanamine-based antivirals and discovered a potent inhibitor M090 against amantadine-resistant viruses, including the 2009 H1N1 pandemic strains, and oseltamivir-resistant viruses. Mechanism of action studies, particularly hemolysis inhibition, indicated that M090 targets influenza HA and it occupied a highly conserved pocket of the HA(2) domain and inhibited virus-mediated membrane fusion by "locking" the bending state of HA(2) during the conformational rearrangement process. This work provides new binding sites within the HA protein and indicates that this pocket may be a promising target for broad-spectrum anti-influenza A drug design and development.

  • 3702.
    Zheng, Daoshan
    et al.
    Mayo Clin, Dept Canc Biol, 4500 San Pablo Rd,Griffin 210, Jacksonville, FL 32224 USA..
    Trynda, Justyna
    Mayo Clin, Dept Canc Biol, 4500 San Pablo Rd,Griffin 210, Jacksonville, FL 32224 USA..
    Williams, Cecilia
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Vold, Jeremy A.
    Mayo Clin, Mayo Canc Registry, 4500 San Pablo Rd, Jacksonville, FL 32224 USA..
    Nguyen, Justin H.
    Mayo Clin, Dept Surg, 4500 San Pablo Rd, Jacksonville, FL 32224 USA.;Mayo Clin, Ctr Canc, 4500 San Pablo Rd, Jacksonville, FL 32224 USA..
    Harnois, Denise M.
    Mayo Clin, Dept Surg, 4500 San Pablo Rd, Jacksonville, FL 32224 USA.;Mayo Clin, Ctr Canc, 4500 San Pablo Rd, Jacksonville, FL 32224 USA..
    Bagaria, Sanjay P.
    Mayo Clin, Dept Surg, 4500 San Pablo Rd, Jacksonville, FL 32224 USA.;Mayo Clin, Ctr Canc, 4500 San Pablo Rd, Jacksonville, FL 32224 USA..
    McLaughlin, Sarah A.
    Mayo Clin, Dept Surg, 4500 San Pablo Rd, Jacksonville, FL 32224 USA.;Mayo Clin, Ctr Canc, 4500 San Pablo Rd, Jacksonville, FL 32224 USA..
    Li, Zhaoyu
    Mayo Clin, Dept Canc Biol, 4500 San Pablo Rd,Griffin 210, Jacksonville, FL 32224 USA..
    Sexual dimorphism in the incidence of human cancers2019Inngår i: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 19, nr 1, artikkel-id 684Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BackgroundSex differences in the incidences of cancers become a critical issue in both cancer research and the development of precision medicine. However, details in these differences have not been well reported. We provide a comprehensive analysis of sexual dimorphism in human cancers.MethodsWe analyzed four sets of cancer incidence data from the SEER (USA, 1975-2015), from the Cancer Registry at Mayo Clinic (1970-2015), from Sweden (1970-2015), and from the World Cancer Report in 2012.ResultsWe found that all human cancers had statistically significant sexual dimorphism with male dominance in the United States and mostly significant in the Mayo Clinic, Sweden, and the world data, except for thyroid cancer, which is female-dominant.ConclusionsSexual dimorphism is a clear but mostly neglected phenotype for most human cancers regarding the clinical practice of cancer. We expect that our study will facilitate the mechanistic studies of sexual dimorphism in human cancers. We believe that fully addressing the mechanisms of sexual dimorphism in human cancers will greatly benefit current development of individualized precision medicine beginning from the sex-specific diagnosis, prognosis, and treatment.

  • 3703.
    Zheng, Daoshan
    et al.
    Dept Canc Biol, 4500 San Pablo Rd, Jacksonville, FL 32224 USA..
    Williams, Cecilia
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Cellulär och klinisk proteomik. KTH, Centra, Science for Life Laboratory, SciLifeLab. Karolinska Institute.
    Vold, Jeremy A.
    Mayo Canc Registry, 4500 San Pablo Rd, Jacksonville, FL 32224 USA..
    Nguyen, Justin H.
    Mayo Clin, Dept Surg, 4500 San Pablo Rd, Jacksonville, FL 32224 USA.;Mayo Clin, Mayo Clin Canc Ctr, 4500 San Pablo Rd, Jacksonville, FL 32224 USA..
    Harnois, Denise M.
    Mayo Clin, Dept Surg, 4500 San Pablo Rd, Jacksonville, FL 32224 USA.;Mayo Clin, Mayo Clin Canc Ctr, 4500 San Pablo Rd, Jacksonville, FL 32224 USA..
    Bagaria, Sanjay P.
    Mayo Clin, Dept Surg, 4500 San Pablo Rd, Jacksonville, FL 32224 USA.;Mayo Clin, Mayo Clin Canc Ctr, 4500 San Pablo Rd, Jacksonville, FL 32224 USA..
    McLaughlin, Sarah A.
    Mayo Clin, Dept Surg, 4500 San Pablo Rd, Jacksonville, FL 32224 USA.;Mayo Clin, Mayo Clin Canc Ctr, 4500 San Pablo Rd, Jacksonville, FL 32224 USA..
    Li, Zhaoyu
    Dept Canc Biol, 4500 San Pablo Rd, Jacksonville, FL 32224 USA..
    Regulation of sex hormone receptors in sexual dimorphism of human cancers2018Inngår i: Cancer Letters, ISSN 0304-3835, E-ISSN 1872-7980, Vol. 438, s. 24-31Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Gender differences in the incidences of cancers have been found in almost all human cancers. However, the mechanisms that underlie gender disparities in most human cancer types have been under-investigated. Here, we provide a comprehensive overview of potential mechanisms underlying sexual dimorphism of each cancer regarding sex hormone signaling. Fully addressing the mechanisms of sexual dimorphism in human cancers will greatly benefit current development of precision medicine. Our discussions of potential mechanisms underlying sexual dimorphism in each cancer will be instructive for future cancer research on gender disparities.

  • 3704.
    Zheng, W.
    et al.
    Department of Laboratory Medicine, Karolinska Institute, Huddinge, 141 86, Sweden.
    Boada, R.
    Centre GTS, Department of Chemistry, Autonomous University of Barcelona, Barcelona, 08193, Spain.
    He, R.
    Department of Laboratory Medicine, Karolinska Institute, Huddinge, 141 86, Sweden.
    Xiao, T.
    Centre GTS, Department of Chemistry, Autonomous University of Barcelona, Barcelona, 08193, Spain.
    Fei, Ye
    KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik, Material- och nanofysik.
    Simonelli, L.
    CELLS-ALBA Synchrotron Radiation Facility, Carrer de la Llum 2-26, Barcelona, 08290, Spain.
    Valiente, M.
    Centre GTS, Department of Chemistry, Autonomous University of Barcelona, Barcelona, 08193, Spain.
    Zhao, Y.
    Department of Laboratory Medicine, Karolinska Institute, Huddinge, 141 86, Sweden. ECM, Clinical Research Center, Karolinska University Hospital, Huddinge, 141 86, Sweden.
    Hassan, M.
    Department of Laboratory Medicine, Karolinska Institute, Huddinge, 141 86, Sweden. ECM, Clinical Research Center, Karolinska University Hospital, Huddinge, 141 86, Sweden.
    Extracellular albumin covalently sequesters selenocompounds and determines cytotoxicity2019Inngår i: International Journal of Molecular Sciences, ISSN 1661-6596, Vol. 20, nr 19, artikkel-id 4734Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Selenocompounds (SeCs) are well-known nutrients and promising candidates for cancer therapy; however, treatment efficacy is very heterogeneous and the mechanism of action is not fully understood. Several SeCs have been reported to have albumin-binding ability, which is an important factor in determining the treatment efficacy of drugs. In the present investigation, we hypothesized that extracellular albumin might orchestrate SeCs efficacy. Four SeCs representing distinct categories were selected to investigate their cytotoxicity, cellular uptake, and species transformation. Concomitant treatment of albumin greatly decreased cytotoxicity and cellular uptake of SeCs. Using both X-ray absorption spectroscopy and hyphenated mass spectrometry, we confirmed the formation of macromolecular conjugates between SeCs and albumin. Although the conjugate was still internalized, possibly via albumin scavenger receptors expressed on the cell surface, the uptake was strongly inhibited by excess albumin. In summary, the present investigation established the importance of extracellular albumin binding in determining SeCs cytotoxicity. Due to the fact that albumin content is higher in humans and animals than in cell cultures, and varies among many patient categories, our results are believed to have high translational impact and clinical implications.

  • 3705. Zheng, Zongli
    et al.
    Advani, Abdolreza
    Melefors, Öjar
    Glavas, Steve
    Nordström, Henrik
    Ye, Weimin
    Engstrand, Lars
    Andersson, Anders F.
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Titration-free 454 sequencing using Y adapters2011Inngår i: Nature Protocols, ISSN 1754-2189, E-ISSN 1750-2799, Vol. 6, nr 9, s. 1367-1376Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We describe a protocol for construction and quantification of libraries for emulsion PCR (emPCR)-based sequencing platforms such as Roche 454 or Ion Torrent PGM. The protocol involves library construction using customized Y adapters, quantification using TaqMan-MGB (minor groove binder) probe-based quantitative PCR (qPCR) and calculation of an optimal template-to-bead ratio based on Poisson statistics, thereby avoiding the need for a laborious titration assay. Unlike other qPCR methods, the TaqMan-MGB probe specifically quantifies effective libraries in molar concentration and does not require specialized equipment. A single quality control step prior to emulsion PCR ensures that libraries contain no adapter dimers and have an optimal length distribution. The presented protocol takes similar to 7 h to prepare eight barcoded libraries from genomic DNA into libraries that are ready to use for full-scale emPCR. It will be useful, for example, to allow analyses of precious clinical samples and amplification-free metatranscriptomics.

  • 3706.
    Zhou, Guang-Quan
    et al.
    Southeast Univ, Sch Biol Sci & Med Engn, Nanjing, Jiangsu, Peoples R China.;Southeast Univ, Natl Demonstrat Ctr Expt Biomed Engn Educ, Nanjing, Jiangsu, Peoples R China..
    Zhang, Yi
    Southeast Univ, Sch Biol Sci & Med Engn, Nanjing, Jiangsu, Peoples R China.;Southeast Univ, Natl Demonstrat Ctr Expt Biomed Engn Educ, Nanjing, Jiangsu, Peoples R China..
    Wang, Ruo-Li
    KTH, Skolan för teknikvetenskap (SCI), Mekanik. KTH, Skolan för teknikvetenskap (SCI), Centra, BioMEx. Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden..
    Zhou, Ping
    Southeast Univ, Sch Biol Sci & Med Engn, Nanjing, Jiangsu, Peoples R China.;Southeast Univ, Natl Demonstrat Ctr Expt Biomed Engn Educ, Nanjing, Jiangsu, Peoples R China..
    Zheng, Yong-Ping
    Hong Kong Polytech Univ, Dept Biomed Engn, Hong Kong, Hong Kong, Peoples R China..
    Tarassova, Olga
    Swedish Sch Sport & Hlth Sci, Stockholm, Sweden..
    Arndt, Anton
    Swedish Sch Sport & Hlth Sci, Stockholm, Sweden.;Karolinska Inst, Dept Clin Intervent & Technol, Stockholm, Sweden..
    Chen, Qiang
    Southeast Univ, Sch Biol Sci & Med Engn, Nanjing, Jiangsu, Peoples R China.;Southeast Univ, Natl Demonstrat Ctr Expt Biomed Engn Educ, Nanjing, Jiangsu, Peoples R China..
    Automatic Myotendinous Junction Tracking in Ultrasound Images with Phase-Based Segmentation2018Inngår i: BioMed Research International, ISSN 2314-6133, E-ISSN 2314-6141, artikkel-id 3697835Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Displacement of the myotendinous junction (MTJ) obtained by ultrasound imaging is crucial to quantify the interactive length changes of muscles and tendons for understanding the mechanics and pathological conditions of the muscle-tendon unit during motion. However, the lack of a reliable automatic measurement method restricts its application in human motion analysis. This paper presents an automated measurement of MTJ displacement using prior knowledge on tendinous tissues and MTJ, precluding the influence of nontendinous components on the estimation of MTJ displacement. It is based on the perception of tendinous features from musculoskeletal ultrasound images using Radon transform and thresholding methods, with information about the symmetric measures obtained from phase congruency. The displacement of MTJ is achieved by tracking manually marked points on tendinous tissues with the Lucas-Kanade optical flow algorithm applied over the segmented MTJ region. The performance of this method was evaluated on ultrasound images of the gastrocnemius obtained from 10 healthy subjects (26.0 +/- 2.9 years of age). Waveform similarity between the manual and automatic measurements was assessed by calculating the overall similarity with the coefficient ofmultiple correlation (CMC). In vivo experiments demonstrated that MTJ tracking with the proposedmethod (CMC = 0.97 +/- 0.02) was more consistent with the manual measurements than existing optical flow tracking methods (CMC = 0.79 +/- 0.11). This study demonstrated that the proposed method was robust to the interference of nontendinous components, resulting in a more reliable measurement of MTJ displacement, whichmay facilitate further research and applications related to the architectural change of muscles and tendons.

  • 3707.
    Zhou, Xiamo
    et al.
    KTH, Skolan för elektro- och systemteknik (EES), Mikro- och nanosystemteknik.
    Carlborg, Carl Fredrik
    KTH, Skolan för elektro- och systemteknik (EES), Mikro- och nanosystemteknik.
    Sandström, Niklas
    KTH, Skolan för elektro- och systemteknik (EES), Mikro- och nanosystemteknik.
    Vastesson, Alexander
    KTH, Skolan för elektro- och systemteknik (EES), Mikro- och nanosystemteknik.
    Saharil, Farizah
    KTH, Skolan för elektro- och systemteknik (EES), Mikro- och nanosystemteknik.
    van der Wijngaart, Wouter
    KTH, Skolan för elektro- och systemteknik (EES), Mikro- och nanosystemteknik.
    Haraldsson, Tommy
    KTH, Skolan för elektro- och systemteknik (EES), Mikro- och nanosystemteknik.
    OSTE+ microfluidic devices with lithographically defined hydrophobic/ hydrophilic patterns and biocompatible chip sealing: OSTEmer Allows Easy Fabrication of Microfluidic Chips2014Inngår i: DIATECH 2014, 2014, s. 26-27Konferansepaper (Fagfellevurdert)
  • 3708.
    Zhou, Xiamo
    et al.
    KTH, Skolan för elektro- och systemteknik (EES), Mikro- och nanosystemteknik.
    Suderleith, Florian
    KTH, Skolan för elektro- och systemteknik (EES), Mikro- och nanosystemteknik.
    Stanke, Sandra
    KTH, Skolan för elektro- och systemteknik (EES), Mikro- och nanosystemteknik.
    van der Wijngaart, Wouter
    KTH, Skolan för elektro- och systemteknik (EES), Mikro- och nanosystemteknik.
    Haraldsson, Tommy
    KTH, Skolan för elektro- och systemteknik (EES), Mikro- och nanosystemteknik.
    Ultrarapid synthesis of microbeads with tuneable surface probe density2016Inngår i: Ultrarapid synthesis of microbeads with tuneable surface probe density, Shanghai, China: IEEE conference proceedings, 2016, Vol. 2016, s. 731-734Konferansepaper (Fagfellevurdert)
    Abstract [en]

    We present, for the first time, a simplified and ultrarapid (~ 1s) approach for synthesis of microbeads with thiol- functionalized surfaces as potential binding sites, whose density can be tuned according to the ratio of two components in the prepolymer. We verify the successful generation of microbeads and their tuneable surface density resulted from different prepolymer off-stoichiometric ratio. This novel approach can be used for bioassays that require rapid surface capture probe binding and customized probe density for suitable bioreactions.

  • 3709.
    Zhou, Xiamo
    et al.
    KTH, Skolan för elektro- och systemteknik (EES), Mikro- och nanosystemteknik.
    Sun, Yang
    KTH, Skolan för kemivetenskap (CHE), Fiber- och polymerteknologi, Polymerteknologi.
    Finne Wistrand, Anna
    KTH, Skolan för kemivetenskap (CHE), Fiber- och polymerteknologi, Polymerteknologi.
    van der Wijngaart, Wouter
    KTH, Skolan för elektro- och systemteknik (EES), Mikro- och nanosystemteknik.
    Haraldsson, Tommy
    KTH, Skolan för elektro- och systemteknik (EES), Mikro- och nanosystemteknik.
    Core-Shell Microparticle Synthesis In Droplet Microfluidics Using A Single Step Polymerization2015Inngår i: Micro Electro Mechanical Systems (MEMS), 2015 28th IEEE International Conference on, IEEE conference proceedings, 2015, s. 472-475Konferansepaper (Fagfellevurdert)
    Abstract [en]

    We present, for the first time, a method for the synthesis of core-shell microparticles in a single polymerization step using two-phase droplet microfluidics. We verify the successful generation of core-shell microparticles using the novel synthesis approach. 

  • 3710.
    Zhou, Zhou
    et al.
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Medicinteknik och hälsosystem, Neuronik.
    Li, Xiaogai
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Medicinteknik och hälsosystem, Neuronik.
    Kleiven, Svein
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Medicinteknik och hälsosystem, Neuronik.
    Biomechanics of acute subdural hematoma in the elderly: A fluid-structure interaction study2019Inngår i: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 36, nr 13, s. 2099-2108Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Acute subdural hematoma (ASDH) due to bridging vein (BV) rupture is a frequent and lethal head injury, especially in the elderly. Brain atrophy has been hypothesized to be a primary pathogenesis associated with the increased risk of ASDH in the elderly. Though decades of biomechanical endeavours have been made to elucidate the potential mechanisms, a thorough explanation for this hypothesis appears lacking. Thus, a recently improved finite element head model, in which the brain-skull interface was modelled using a fluid-structure interaction (FSI) approach with special treatment of the cerebrospinal fluid as arbitrary Lagrangian-Eulerian fluid formulation, is used to partially address this understanding gap. Models with various degrees of atrophied brains and thereby different subarachnoid thicknesses are generated and subsequently exposed to experimentally determined loadings known to cause ASDH or not. The results show significant increases in the cortical relative motion and BV strain in the atrophied brain, which consequently exacerbates the ASDH risk in the elderly. Results of this study are suggested to be considered while developing age-adapted protecting strategies for the elderly in the future.

  • 3711.
    Zhou, Zhou
    et al.
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Medicinteknik och hälsosystem, Neuronik.
    Li, Xiaogai
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Medicinteknik och hälsosystem, Neuronik.
    Kleiven, Svein
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Medicinteknik och hälsosystem, Neuronik.
    Shah, Chirag S.
    Hardy, Warren N.
    A Reanalysis of Experimental Brain Strain Data: Implication for Finite Element Head Model Validation2019Inngår i: SAE Technical Papers, SAE International , 2019, Vol. 2019, artikkel-id NovemberKonferansepaper (Fagfellevurdert)
    Abstract [en]

    Relative motion between the brain and skull and brain deformation are biomechanics aspects associated with many types of traumatic brain injury (TBI). Thus far, there is only one experimental endeavor (Hardy et al., 2007) reported brain strain under loading conditions commensurate with levels that were capable of producing injury. Most of the existing finite element (FE) head models are validated against brain-skull relative motion and then used for TBI prediction based on strain metrics. However, the suitability of using a model validated against brain-skull relative motion for strain prediction remains to be determined. To partially address the deficiency of experimental brain deformation data, this study revisits the only existing dynamic experimental brain strain data and updates the original calculations, which reflect incremental strain changes. The brain strain is recomputed by imposing the measured motion of neutral density target (NDT) to the NDT triad model. The revised brain strain and the brain-skull relative motion data are then used to test the hypothesis that an FE head model validated against brain-skull relative motion does not guarantee its accuracy in terms of brain strain prediction. To this end, responses of brain strain and brain-skull relative motion of a previously developed FE head model (Kleiven, 2007) are compared with available experimental data. CORrelation and Analysis (CORA) and Normalized Integral Square Error (NISE) are employed to evaluate model validation performance for both brain strain and brain-skull relative motion. Correlation analyses (Pearson coefficient) are conducted between average cluster peak strain and average cluster peak brain-skull relative motion, and also between brain strain validation scores and brain-skull relative motion validation scores. The results show no significant correlations, neither between experimentally acquired peaks nor between computationally determined validation scores. These findings indicate that a head model validated against brain-skull relative motion may not be sufficient to assure its strain prediction accuracy. It is suggested that a FE head model with intended use for strain prediction should be validated against the experimental brain deformation data and not just the brain-skull relative motion.

  • 3712.
    Zhou, Zhou
    et al.
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Medicinteknik och hälsosystem, Neuronik.
    Li, Xiaogai
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Medicinteknik och hälsosystem, Neuronik.
    Kleiven, Svein
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Medicinteknik och hälsosystem, Neuronik.
    Shah, C.S.
    Hardy, W.N.
    A reanalysis of experimental brain strain data: implication for finite element head model validation2018Inngår i: Stapp Car Crash Journal, ISSN 1532-8546, Vol. 62, s. 293-318Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Relative motion between the brain and skull and brain deformation are biomechanics aspects associated with many types of traumatic brain injury (TBI). Thus far, there is only one experimental endeavor (Hardy et al., 2007) reported brain strain under loading conditions commensurate with levels that were capable of producing injury. Most of the existing finite element (FE) head models are validated against brain-skull relative motion and then used for TBI prediction based on strain metrics. However, the suitability of using a model validated against brain-skull relative motion for strain prediction remains to be determined. To partially address the deficiency of experimental brain deformation data, this study revisits the only existing dynamic experimental brain strain data and updates the original calculations, which reflect incremental strain changes. The brain strain is recomputed by imposing the measured motion of neutral density target (NDT) to the NDT triad model. The revised brain strain and the brain-skull relative motion data are then used to test the hypothesis that an FE head model validated against brainskull relative motion does not guarantee its accuracy in terms of brain strain prediction. To this end, responses of brain strain and brain-skull relative motion of a previously developed FE head model (Kleiven, 2007) are compared with available experimental data. CORrelation and Analysis (CORA) and Normalized Integral Square Error (NISE) are employed to evaluate model validation performance for both brain strain and brain-skull relative motion. Correlation analyses (Pearson coefficient) are conducted between average cluster peak strain and average cluster peak brain-skull relative motion, and also between brain strain validation scores and brain-skull relative motion validation scores. The results show no significant correlations, neither between experimentally acquired peaks nor between computationally determined validation scores. These findings indicate that a head model validated against brain-skull relative motion may not be sufficient to assure its strain prediction accuracy. It is suggested that a FE head model with intended use for strain prediction should be validated against the experimental brain deformation data and not just the brain-skull relative motion.

  • 3713.
    Zhu, Bin
    et al.
    KTH, Skolan för datavetenskap och kommunikation (CSC), Medieteknik och interaktionsdesign, MID. China Academy of Art, China.
    Hedman, Anders
    KTH, Skolan för datavetenskap och kommunikation (CSC), Medieteknik och interaktionsdesign, MID.
    Feng, Shuo
    KTH, Skolan för datavetenskap och kommunikation (CSC).
    Li, Haibo
    KTH, Skolan för datavetenskap och kommunikation (CSC), Medieteknik och interaktionsdesign, MID.
    Osika, Walter
    Designing, Prototyping and Evaluating Digital Mindfulness Applications: A Case Study of Mindful Breathing for Stress Reduction2017Inngår i: Journal of Medical Internet Research, ISSN 1438-8871, E-ISSN 1438-8871, Vol. 19, nr 6, artikkel-id e197Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: During the past decade, there has been a rapid increase of interactive apps designed for health and well-being. Yet, little research has been published on developing frameworks for design and evaluation of digital mindfulness facilitating technologies. Moreover, many existing digital mindfulness applications are purely software based. There is room for further exploration and assessment of designs that make more use of physical qualities of artifacts. Objective: The study aimed to develop and test a new physical digital mindfulness prototype designed for stress reduction. Methods: In this case study, we designed, developed, and evaluated HU, a physical digital mindfulness prototype designed for stress reduction. In the first phase, we used vapor and light to support mindful breathing and invited 25 participants through snowball sampling to test HU. In the second phase, we added sonification. We deployed a package of probes such as photos, diaries, and cards to collect data from users who explored HU in their homes. Thereafter, we evaluated our installation using both self-assessed stress levels and heart rate (HR) and heart rate variability (HRV) measures in a pilot study, in order to measure stress resilience effects. After the experiment, we performed a semistructured interview to reflect on HU and investigate the design of digital mindfulness apps for stress reduction. Results: The results of the first phase showed that 22 of 25 participants (88%) claimed vapor and light could be effective ways of promoting mindful breathing. Vapor could potentially support mindful breathing better than light (especially for mindfulness beginners). In addition, a majority of the participants mentioned sound as an alternative medium. In the second phase, we found that participants thought that HU could work well for stress reduction. We compared the effect of silent HU (using light and vapor without sound) and sonified HU on 5 participants. Subjective stress levels were statistically improved with both silent and sonified HU. The mean value of HR using silent HU was significantly lower than resting baseline and sonified HU. The mean value of root mean square of differences (RMSSD) using silent HU was significantly higher than resting baseline. We found that the differences between our objective and subjective assessments were intriguing and prompted us to investigate them further. Conclusions: Our evaluation of HU indicated that HU could facilitate relaxed breathing and stress reduction. There was a difference in outcome between the physiological measures of stress and the subjective reports of stress, as well as a large intervariability among study participants. Our conclusion is that the use of stress reduction tools should be customized and that the design work of mindfulness technology for stress reduction is a complex process, which requires cooperation of designers, HCI (Human-Computer Interaction) experts and clinicians.

  • 3714.
    Zhu, Bin
    et al.
    KTH.
    Kürth-Landwehr, S.
    Corbi, Victor Guerrero
    KTH.
    YU: An artistic exploration of interface design for home healthcare2014Inngår i: TEI '14 Proceedings of the 8th International Conference on Tangible, Embedded and Embodied Interaction, 2014, s. 332-334Konferansepaper (Fagfellevurdert)
    Abstract [en]

    YU is an artistic home healthcare system including measuring, visualizing and displaying personal bio-data as well as biofeedback. It integrates with the home setting and aims for bringing aesthetic experience. Through the system YU, we explore possibilities of design health technologies with artistic interface into our home life. Instead of commonly used numeric or graphical interface, we use Chinese ink painting to visualize the pulse and HRV (Heart Rate Variability). We design an artistic interface with two display modes and three levels of interactivity involving in the home life.

  • 3715.
    Zhu, Fei
    et al.
    Univ Edinburgh, Genes Cognit Program, Ctr Clin Brain Sci, Edinburgh EH16 4SB, Midlothian, Scotland.;UCL Inst Neurol, Queen Sq, London WC1N 3BG, England..
    Cizeron, Melissa
    Univ Edinburgh, Genes Cognit Program, Ctr Clin Brain Sci, Edinburgh EH16 4SB, Midlothian, Scotland.;Univ Claude Bernard Lyon 1, Univ Lyon, Inst NeuroMyoGene, CNRS,UMR 5310,INSERM,U1217, F-69008 Lyon, France..
    Qiu, Zhen
    Univ Edinburgh, Genes Cognit Program, Ctr Clin Brain Sci, Edinburgh EH16 4SB, Midlothian, Scotland..
    Benavides-Piccione, Ruth
    CSIC, Inst Cajal, E-28002 Madrid, Spain.;UPM, Ctr Tecnol Biomed, Madrid 28223, Spain.;ISCIII, CIBERNED, Madrid 28031, Spain..
    Kopanitsa, Maksym V.
    Synome Ltd, Babraham Res Campus, Cambridge CB22 3AT, England.;Imperial Coll London, UK Dementia Res Inst, London W12 0NN, England..
    Skene, Nathan G.
    Univ Edinburgh, Genes Cognit Program, Ctr Clin Brain Sci, Edinburgh EH16 4SB, Midlothian, Scotland.;UCL Inst Neurol, Queen Sq, London WC1N 3BG, England.;Karolinska Inst, Dept Med Biochem & Biophys, Lab Mol Neurobiol, S-17177 Stockholm, Sweden..
    Koniaris, Babis
    Univ Edinburgh, Genes Cognit Program, Ctr Clin Brain Sci, Edinburgh EH16 4SB, Midlothian, Scotland..
    DeFelipe, Javier
    CSIC, Inst Cajal, E-28002 Madrid, Spain.;UPM, Ctr Tecnol Biomed, Madrid 28223, Spain.;ISCIII, CIBERNED, Madrid 28031, Spain..
    Fransén, Erik
    KTH, Skolan för elektroteknik och datavetenskap (EECS), Beräkningsvetenskap och beräkningsteknik (CST).
    Komiyama, Noboru H.
    Univ Edinburgh, Genes Cognit Program, Ctr Clin Brain Sci, Edinburgh EH16 4SB, Midlothian, Scotland..
    Grant, Seth G. N.
    Univ Edinburgh, Genes Cognit Program, Ctr Clin Brain Sci, Edinburgh EH16 4SB, Midlothian, Scotland..
    Architecture of the Mouse Brain Synaptome2018Inngår i: Neuron, ISSN 0896-6273, E-ISSN 1097-4199, Vol. 99, nr 4, s. 781-+Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Synapses are found in vast numbers in the brain and contain complex proteomes. We developed genetic labeling and imaging methods to examine synaptic proteins in individual excitatory synapses across all regions of the mouse brain. Synapse catalogs were generated from the molecular and morphological features of a billion synapses. Each synapse subtype showed a unique anatomical distribution, and each brain region showed a distinct signature of synapse subtypes. Whole-brain synaptome cartography revealed spatial architecture from dendritic to global systems levels and previously unknown anatomical features. Synaptome mapping of circuits showed correspondence between synapse diversity and structural and functional connectomes. Behaviorally relevant patterns of neuronal activity trigger spatio-temporal postsynaptic responses sensitive to the structure of synaptome maps. Areas controlling higher cognitive function contain the greatest synapse diversity, and mutations causing cognitive disorders reorganized synaptome maps. Synaptome technology and resources have wide-ranging application in studies of the normal and diseased brain.

  • 3716. Zhu, Huilin
    et al.
    Fan, Yuebo
    Guo, Huan
    Huang, Dan
    He, Sailing
    KTH, Skolan för elektro- och systemteknik (EES), Elektroteknisk teori och konstruktion. KTH, Skolan för informations- och kommunikationsteknik (ICT), Centra, Zhejiang-KTH Joint Research Center of Photonics, JORCEP.
    Reduced interhemispheric functional connectivity of children with autism spectrum disorder: evidence from functional near infrared spectroscopy studies2014Inngår i: Biomedical Optics Express, ISSN 2156-7085, E-ISSN 2156-7085, Vol. 5, nr 4, s. 1262-1274Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Autism spectrum disorder (ASD) is a neuro-developmental disorder, which has been associated with atypical neural synchronization. In this study, functional near infrared spectroscopy (fNIRS) was used to study the differences in functional connectivity in bilateral inferior frontal cortices (IFC) and bilateral temporal cortices (TC) between ASD and typically developing (TD) children between 8 and 11 years of age. As the first report of fNIRS study on the resting state functional connectivity (RSFC) in children with ASD, ten children with ASD and ten TD children were recruited in this study for 8 minute resting state measurement. Compared to TD children, children with ASD showed reduced interhemispheric connectivity in TC. Children with ASD also showed significantly lower local connectivity in bilateral temporal cortices. In contrast to TD children, children with ASD did not show typical patterns of symmetry in functional connectivity in temporal cortex. These results support the feasibility of using the fNIRS method to assess atypical functional connectivity of cortical responses of ASD and its potential application in diagnosis.

  • 3717. Zhu, J
    et al.
    Zhao, C
    Kharman-Biz, A
    Zhuang, T
    Jonsson, P
    Liang, N
    Williams, Cecilia
    University of Houston, United States .
    Lin, C-Y
    Qiao, Y
    Zendehdel, K
    Strömblad, S
    Treuter, E
    Dahlman-Wright, K
    The atypical ubiquitin ligase RNF31 stabilizes estrogen receptor α and modulates estrogen-stimulated breast cancer cell proliferation.2014Inngår i: Oncogene, ISSN 0950-9232, E-ISSN 1476-5594, Vol. 33, nr 34, s. 4340-4351Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Estrogen receptor α (ERα) is initially expressed in the majority of breast cancers and promotes estrogen-dependent cancer progression by regulating the transcription of genes linked to cell proliferation. ERα status is of clinical importance, as ERα-positive breast cancers can be successfully treated by adjuvant therapy with antiestrogens or aromatase inhibitors. Complications arise from the frequent development of drug resistance that might be caused by multiple alterations, including components of ERα signaling, during tumor progression and metastasis. Therefore, insights into the molecular mechanisms that control ERα expression and stability are of utmost importance to improve breast cancer diagnostics and therapeutics. Here we report that the atypical E3 ubiquitin ligase RNF31 stabilizes ERα and facilitates ERα-stimulated proliferation in breast cancer cell lines. We show that depletion of RNF31 decreases the number of cells in the S phase and reduces the levels of ERα and its downstream target genes, including cyclin D1 and c-myc. Analysis of data from clinical samples confirms correlation between RNF31 expression and the expression of ERα target genes. Immunoprecipitation indicates that RNF31 associates with ERα and increases its stability and mono-ubiquitination, dependent on the ubiquitin ligase activity of RNF31. Our data suggest that association of RNF31 and ERα occurs mainly in the cytosol, consistent with the lack of RNF31 recruitment to ERα-occupied promoters. In conclusion, our study establishes a non-genomic mechanism by which RNF31 via stabilizing ERα levels controls the transcription of estrogen-dependent genes linked to breast cancer cell proliferation.

  • 3718. Zhu, J.
    et al.
    Zhao, C.
    Zhuang, T.
    Jonsson, P.
    Sinha, I.
    Williams, Cecilia
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Strömblad, S.
    Dahlman-Wright, K.
    RING finger protein 31 promotes p53 degradation in breast cancer cells2016Inngår i: Oncogene, ISSN 0950-9232, E-ISSN 1476-5594, Vol. 35, nr 15, s. 1955-1964Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The atypical E3 ubiquitin ligase RNF31 is highly expressed in human breast cancer, the most frequent neoplastic lethality among women. Here, RNF31 depletion in breast cancer cells in combination with global gene expression profiling revealed p53 (TP53) signaling as a potential RNF31 target. Interestingly, RNF31 decreased p53 stability, whereas depletion of RNF31 in breast cancer cells caused cell cycle arrest and cisplatin-induced apoptosis in a p53-dependent manner. Furthermore, RNF31 associated with the p53/MDM2 complex and facilitated p53 polyubiquitination and degradation by stabilizing MDM2, suggesting a molecular mechanism by which RNF31 regulates cell death. Analysis of publically available clinical data sets displayed a negative correlation between RNF31 and p53 target genes, including IGFBP3 and BTG1, consistent with RNF31 regulating p53 function in vivo as well. Together, our findings suggest RNF31 as a potential therapeutic target to restore p53 function in breast cancer.

  • 3719.
    Zieba, Agata
    et al.
    Uppsala Univ, Dept Immunol Genet & Pathol, Sci Life Lab, S-75185 Uppsala, Sweden..
    Sjöstedt, Evelina
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Olovsson, Matts
    Uppsala Univ, Dept Womens & Childrens Hlth, S-75185 Uppsala, Sweden..
    Fagerberg, Linn
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Hallström, Björn M.
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Oskarsson, Linda
    Uppsala Univ, Dept Immunol Genet & Pathol, Sci Life Lab, S-75185 Uppsala, Sweden..
    Edlund, Karolina
    Uppsala Univ, Dept Immunol Genet & Pathol, Sci Life Lab, S-75185 Uppsala, Sweden..
    Tolf, Anna
    Uppsala Univ, Dept Immunol Genet & Pathol, Sci Life Lab, S-75185 Uppsala, Sweden..
    Uhlén, Mathias
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Ponten, Fredrik
    Uppsala Univ, Dept Immunol Genet & Pathol, Sci Life Lab, S-75185 Uppsala, Sweden..
    The Human Endometrium-Specific Proteome Defined by Transcriptomics and Antibody-Based Profiling2015Inngår i: Omics, ISSN 1536-2310, E-ISSN 1557-8100, Vol. 19, nr 11, s. 659-668Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The human uterus includes the complex endometrial mucosa, the endometrium that undergoes dynamic, hormone-dependent alterations throughout the life of fertile females. Here we have combined a genome-wide transcriptomics analysis with immunohistochemistry-based protein profiling to analyze gene expression patterns in the normal endometrium. Human endometrial tissues from five women were used for deep sequencing (RNA-Seq). The mRNA and protein expression data from the endometrium were compared to 31 (RNA) and 44 (protein) other normal tissue types, to identify genes with elevated expression in the endometrium and to localize the expression of corresponding proteins at a cellular resolution. Based on the expression levels of transcripts, we could classify all putative human protein coding genes into categories defined by expression patterns and found altogether 101 genes that showed an elevated pattern of expression in the endometrium, with only four genes showing more than five-fold higher expression levels in the endometrium compared to other tissues. In conclusion, our analysis based on transcriptomics and antibody-based protein profiling reports here comprehensive lists of genes with elevated expression levels in the endometrium, providing important starting points for a better molecular understanding of human reproductive biology and disease.

  • 3720. Zong, N. C.
    et al.
    Li, H.
    Lam, M. P. Y.
    Jimenez, R. C.
    Kim, C. S.
    Deng, N.
    Kim, A. K.
    Choi, J. H.
    Zelaya, I.
    Liem, D.
    Meyer, D.
    Odeberg, Jacob
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Fang, C.
    Lu, H. -J
    Xu, T.
    Weiss, J.
    Duan, H.
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Yates III, J. R.
    Apweiler, R.
    Ge, J.
    Hermjakob, H.
    Ping, P.
    Integration of cardiac proteome biology and medicine by a specialized knowledgebase2013Inngår i: Circulation Research, ISSN 0009-7330, E-ISSN 1524-4571, Vol. 113, nr 9, s. 1043-1053Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Rationale: Omics sciences enable a systems-level perspective in characterizing cardiovascular biology. Integration of diverse proteomics data via a computational strategy will catalyze the assembly of contextualized knowledge, foster discoveries through multidisciplinary investigations, and minimize unnecessary redundancy in research efforts. Objective: The goal of this project is to develop a consolidated cardiac proteome knowledgebase with novel bioinformatics pipeline and Web portals, thereby serving as a new resource to advance cardiovascular biology and medicine. Methods and results: We created Cardiac Organellar Protein Atlas Knowledgebase (COPaKB; www.HeartProteome.org), a centralized platform of high-quality cardiac proteomic data, bioinformatics tools, and relevant cardiovascular phenotypes. Currently, COPaKB features 8 organellar modules, comprising 4203 LC-MS/MS experiments from human, mouse, drosophila, and Caenorhabditis elegans, as well as expression images of 10 924 proteins in human myocardium. In addition, the Java-coded bioinformatics tools provided by COPaKB enable cardiovascular investigators in all disciplines to retrieve and analyze pertinent organellar protein properties of interest. Conclusions: COPaKB provides an innovative and interactive resource that connects research interests with the new biological discoveries in protein sciences. With an array of intuitive tools in this unified Web server, nonproteomics investigators can conveniently collaborate with proteomics specialists to dissect the molecular signatures of cardiovascular phenotypes.

  • 3721.
    Zou, Rongfeng
    et al.
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Teoretisk kemi och biologi.
    Guanglin, Kuang
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Teoretisk kemi och biologi.
    Ågren, Hans
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Teoretisk kemi och biologi. Henan Univ, Coll Chem & Chem Engn, Kaifeng 475004, Henan, Peoples R China..
    Nordberg, Agneta
    Karolinska Univ Hosp, Karolinska Inst, Dept Neurobiol Care Sci & Soc, Ctr Alzheimer Res,Clin Geriatr Neo & Theme Aging, S-14183 Huddinge, Sweden..
    Långström, Bengt
    Uppsala Univ, Phys Organ Chem, Dept Chem, BMC, S-75123 Uppsala, Sweden..
    Tu, Yaoquan
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Teoretisk kemi och biologi.
    Free Energy Profile for Penetration of Pittsburgh Compound-B into the Amyloid beta Fibril2019Inngår i: ACS Chemical Neuroscience, ISSN 1948-7193, E-ISSN 1948-7193, Vol. 10, nr 3, s. 1783-1790Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The amyloid beta (A beta) fibril is a hallmark of Alzheimer's disease (AD) and has therefore served as an important target for early diagnosis of AD. The Pittsburgh Compound-B (PiB) is one of the most famous positron emission tomography (PET) tracers commonly used for in vivo detection of A beta fibrils. Many theoretical studies have predicted the existence of various core binding sites with different microenvironments for probes binding to the A beta fibril. However, little attention has been devoted to how the probes actually penetrate into the different core binding sites. In this study, an integrated molecular modeling scheme is used to study the penetration of PiB into the core binding sites of the A beta(1-42) fibril structure recently obtained by cryogenic electron microscopy. We find that there are two core binding sites for PiB with dramatic differences in cavity size and microenvironment properties, and furthermore that the penetration of PiB into site-1 is energetically prohibitive, whereas the penetration into site 2 is much more favorable. Therefore, the binding capacity at site-2 may be larger than that at site-1 despite its lower binding affinity. Our results thus suggest that site-2 may be a major binding site for PiB binding to A beta fibril and emphasize the importance to adopt a full dynamical picture when studying tracer fibril binding problems in general, something that in turn can be used to guide the development of tracers with higher affinity and selectivity for the A beta fibril.

  • 3722.
    Åberg, Anna Cristina
    et al.
    Swedish School of Sports and Health Sciences.
    Frykberg, Gunilla
    Uppsala University.
    Halvorsen, Kjartan
    The Swedish School of Sport and Health Sciences, Stockholm, Sweden.
    Medio-lateral stability of sit-to-walk performance in older individuals with and without fear of falling2010Inngår i: Gait & Posture, ISSN 0966-6362, E-ISSN 1879-2219, Vol. 31, nr 4, s. 438-443Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Most falls in older people are due to loss of balance during everyday locomotion, e.g., when initiating walking from sitting; sit-to-walk (STW). It has been considered that the broader stride width in walking that is seen in many people with fear of falling (FoF) does not increase stability, but could be predictive of future falls because of increased medio-lateral (ML) velocity of the body centre of mass (CoM). This study was aimed to examine step-, velocity- and stability-related parameters, focusing on ML stability, in STW performance of people with and without FoF. Ten subjects with FoF and 10 matched controls, aged >= 70 years, were included. Kinematic and kinetic data were collected in a laboratory. Stability parameters were calculated from a formula implying that the vertical projection of the CoM extrapolated by adding its velocity times a factor root l/g (height of inverted pendulum divided by gravity) should fall within the base of support (BoS). A related spatial margin of stability (SMoS), defined as the minimum distance from the extrapolated CoM (XCoM) to the boundaries of the BoS, was also calculated. In the phase 'seat-off-second-toe-off, the FoF group had significantly (p < 0.05) shorter and broader steps, lower forward but similar ML CoM velocity, and broader CoM and XCoM widths. The FoF group therefore exhibited a disproportionately large sideways velocity compared to the controls. This indicates that STW may be a hazardous transfer for older people with FoF, which should be relevant in assessment and training aimed at preventing falls.

  • 3723. Åborg, C
    et al.
    Fernström, E
    Ericson, Mats O
    KTH, Skolan för teknik och hälsa (STH), Ergonomi.
    Work content and satisfaction before and after a reorganisation of data entry work.1998Inngår i: Applied Ergonomics, ISSN 0003-6870, E-ISSN 1872-9126, Vol. 29, nr 6, s. 473-80Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The aim of the study was to analyse the psychosocial and physical effects of a reorganisation of data entry work at a data processing unit with 153 employees. The reorganisation was planned to redistribute the repetitive work and improve health and satisfaction as well as efficiency. Methods used were questionnaires and, for a sub-group of 22 participants, interviews, diaries and video recordings. During the one-and-a-half-year study period the data processing unit was closed down and the employees transferred to units with more varied tasks. The reorganisation gave opportunities to improve working conditions. The results of this study show that important improvements were achieved. The majority of the 22 participants got less data entry work and the changes permitted a better work-load distribution. However, the work content after the reorganisation still did not provide satisfactory mental variation for most of the subjects, and the changes did not seem to affect health complaints.

  • 3724.
    Ågerstrand, Marlene
    et al.
    KTH, Skolan för arkitektur och samhällsbyggnad (ABE), Filosofi och teknikhistoria, Filosofi.
    Breitholtz, Magnus
    Stockholm Univ, Stockholm, Sweden .
    Hansson, Sven Ove
    KTH, Skolan för arkitektur och samhällsbyggnad (ABE), Filosofi och teknikhistoria, Filosofi.
    Rudén, Christina
    KTH, Skolan för arkitektur och samhällsbyggnad (ABE), Filosofi och teknikhistoria, Filosofi.
    Regulatory perspectives on pharmaceuticals in the environment2012Inngår i: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 211, s. S31-S31Artikkel i tidsskrift (Annet vitenskapelig)
  • 3725.
    Åkerborg, Örjan
    et al.
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Spalinskas, Rapolas
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Pradhananga, Sailendra
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Anil, Anandashankar
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Höjer, Pontus
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Poujade, Flore-Anne
    Karolinska Inst, Cardiovasc Med Unit, Dept Med, Ctr Mol Med, Stockholm, Sweden..
    Folkersen, Lasse
    Tech Univ Denmark, Dept Bioinformat, Copenhagen, Denmark..
    Sahlén, Pelin
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Eriksson, Per
    Karolinska Inst, Cardiovasc Med Unit, Dept Med, Ctr Mol Med, Stockholm, Sweden..
    High-Resolution Regulatory Maps Connect Vascular Risk Variants to Disease-Related Pathways2019Inngår i: Circulation. Genomic and precision medicine, ISSN 2574-8300, Vol. 12, nr 3, artikkel-id e002353Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Genetic variant landscape of coronary artery disease is dominated by noncoding variants among which many occur within putative enhancers regulating the expression levels of relevant genes. It is crucial to assign the genetic variants to their correct genes both to gain insights into perturbed functions and better assess the risk of disease. METHODS: In this study, we generated high-resolution genomic interaction maps (similar to 750 bases) in aortic endothelial, smooth muscle cells and THP-1 (human leukemia monocytic cell line) macrophages stimulated with lipopolysaccharide using Hi-C coupled with sequence capture targeting 25 429 features, including variants associated with coronary artery disease. We also sequenced their transcriptomes and mapped putative enhancers using chromatin immunoprecipitation with an antibody against H3K27Ac. RESULTS: The regions interacting with promoters showed strong enrichment for enhancer elements and validated several previously known interactions and enhancers. We detected interactions for 727 risk variants obtained by genome-wide association studies and identified novel, as well as established genes and functions associated with cardiovascular diseases. We were able to assign potential target genes for additional 398 genome-wide association studies variants using haplotype information, thereby identifying additional relevant genes and functions. Importantly, we discovered that a subset of risk variants interact with multiple promoters and their expression levels were strongly correlated. CONCLUSIONS: In summary, we present a catalog of candidate genes regulated by coronary artery disease-related variants and think that it will be an invaluable resource to further the investigation of cardiovascular pathologies and disease.

  • 3726. Åkerlund, Emma
    et al.
    Cappellini, Francesca
    Di Bucchianico, Sebastiano
    Islam, Shafiqul
    Skoglund, Sara
    KTH, Skolan för kemivetenskap (CHE), Kemi, Yt- och korrosionsvetenskap.
    Derr, Remco
    Odnevall Wallinder, Inger
    KTH, Skolan för kemivetenskap (CHE), Kemi, Yt- och korrosionsvetenskap.
    Hendriks, Giel
    Karlsson, Hanna L.
    Genotoxic and mutagenic properties of Ni and NiO nanoparticles investigated by comet assay,-H2AX staining, Hprt mutation assay and ToxTracker reporter cell lines2018Inngår i: Environmental and Molecular Mutagenesis, ISSN 0893-6692, E-ISSN 1098-2280, Vol. 59, nr 3, s. 211-222Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Nickel (Ni) compounds are classified as carcinogenic to humans but the underlying mechanisms are still poorly understood. Furthermore, effects related to nanoparticles (NPs) of Ni have not been fully elucidated. The aim of this study was to investigate genotoxicity and mutagenicity of Ni and NiO NPs and compare the effect to soluble Ni from NiCl2. We employed different models; i.e., exposure of (1) human bronchial epithelial cells (HBEC) followed by DNA strand break analysis (comet assay and -H2AX staining); (2) six different mouse embryonic stem (mES) reporter cell lines (ToxTracker) that are constructed to exhibit fluorescence upon the induction of various pathways of relevance for (geno)toxicity and cancer; and (3) mES cells followed by mutagenicity testing (Hprt assay). The results showed increased DNA strand breaks (comet assay) for the NiO NPs and at higher doses also for the Ni NPs whereas no effects were observed for Ni ions/complexes from NiCl2. By employing the reporter cell lines, oxidative stress was observed as the main toxic mechanism and protein unfolding occurred at cytotoxic doses for all three Ni-containing materials. Oxidative stress was also detected in the HBEC cells following NP-exposure. None of these materials induced the reporter related to direct DNA damage and stalled replication forks. A small but statistically significant increase in Hprt mutations was observed for NiO but only at one dose. We conclude that Ni and NiO NPs show more pronounced (geno)toxic effects compared to Ni ions/complexes, indicating more serious health concerns. Environ. Mol. Mutagen. 59:211-222, 2018.

  • 3727. Åkerman, S.
    et al.
    Lindeberg, Tony
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Roland, P.
    Surface Model Generation and Segmentation of the Human Celebral Cortex for the Construction of Unfolded Cortical Maps1996Inngår i: Proc. 2nd International Conference on Functional Mapping of the Human Brain: HBM'96, published in Neuroimage, volume 3, number 3, 1996, s. S126-S126Konferansepaper (Fagfellevurdert)
    Abstract [en]

    Representing the shape of the human cerebral cortex arises as a basic subproblem in several areas of brain science, such as when describing the anatomy of the cortex and when relating functional measurements to cortical regions. 

    Most current methods for building such representions of the cortical surface are either based on contours from two-dimensional cross sections or landmarks that have been obtained manually.

    In this article, we outline a methodology for semi-automatic contruction of a solely surface based representation of the human cerebral cortex in vivo for subsequent generation of  (unfolded) two-dimensional brain maps.

    The method is based on input data in the form of three-dimensional NMR images, and comprises the following main steps:

    • suppression of disturbing fine-scale structures by linear and non-linear scale-space techniques,
    • generation of a triangulated surface representation based on either iso-surfaces or three-dimensional edge detection,
    • division of the surface model into smaller segments based on differential invariants computed from the image data.

    When constructing an unfolded (flattened) surface representation, the instrinsic curvature of the cortex means that such a unfolding cannot be done without introducing distortions. To reduce this problem, we propose to cut the surface into smaller parts, where a ridge detector acts as guideline, and then unfold each patch individually, so as to obtain low distortions.

    Having a solely surface based representation of the cortex and expressing the image operations using multi-scale differential invariants in terms of scale-space derivatives as done in this work is a natural choice both in terms of conceptual and algorithmic simplicity. Moreover, explicitly handling the multi-scale nature of the data is necessary to obtain robust results.

  • 3728.
    Åkerstedt, Josefin
    KTH, Skolan för kemivetenskap (CHE), Kemi, Oorganisk kemi.
    Tailored Reaction Media for the Synthesis of Subvalent Cluster Compounds2010Licentiatavhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Different synthetic approaches and modifications to reaction media have been applied in order to find new routes to the synthesis of main-group clusters and transition metal compounds. The focus has been on the Group 15 element bismuth and the transition metal palladium. The reactions performed have mainly been Lewis acid-base reactions and the characterization tools used X-ray diffraction and Raman spectroscopy.

    The Bi5[GaCl4]3 salt, previously known form synthesis using other reaction routes, has been isolated from GaCl3-dichloromethane media. The salt containing the subvalent naked bismuth polycation Bi53+ was isolated from the reduction of bismuth(III) chloride. Quantum chemical calculations on the interaction energies of the isolated bismuth cluster show the dichloromethane-cluster interaction energy to be higher than that between benzene and the cluster.

    Ionic liquids have, in addition to dichloromethane, been shown to work as alternative reaction media for room-temperature synthesis of the Bi5[GaCl4]3 salt. Three different classes of ionic liquids have been used; phosphonium-, imidazolium- and pyrrolidinium-based salts. The ionic liquids used have been treated with Lewis acids in order to promote cluster formation.

    In this work three new palladium sandwich compounds have also been isolated, using GaCl3-arene reaction media; [Pd2(Ga2Cl7)(C7H8)2], [Pd2(GaCl4)(C9H12)2]∙C9H12 and [Pd2(Ga2Cl7)(C6H5Cl)2]. Quantum chemical calculations on these palladium sandwiches show the chlorobenzene sandwiching ligands unexpectedly interacting more strongly with the dipalladium unit than the methyl substituted arenes.

  • 3729.
    Åkerstedt, Josefin
    et al.
    KTH, Skolan för kemivetenskap (CHE), Kemi, Tillämpad fysikalisk kemi.
    Gorlov, Mikhail
    KTH, Skolan för kemivetenskap (CHE), Kemi, Tillämpad fysikalisk kemi.
    Kloo, Lars
    KTH, Skolan för kemivetenskap (CHE), Kemi, Tillämpad fysikalisk kemi.
    Room-Temperature Synthesis of the Bi-5[GaCl4](3) Salt From Three Different Classes of Ionic Liquids2013Inngår i: Journal of cluster science, ISSN 1040-7278, E-ISSN 1572-8862, Vol. 24, nr 1, s. 157-164Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Following the development in the synthesis of subvalent cluster compounds, we report on the use of three different classes of room-temperature ionic liquids for the synthesis of the pentabismuth-tris(tetragallate) salt, Bi-5[GaCl4](3), characterized by X-ray diffraction. The Bi-5[GaCl4](3) salt was prepared by reduction of BiCl3 using gallium metal in ionic liquid reaction media containing a strong Lewis acid, GaCl3. The ionic liquids; trihexyltetradecyl phosphonium chloride [Th-Td-P+]Cl-, 1-dodecyl-3-methylimidazolium chloride [Dod-Me-Im(+)]Cl- and N-butyl-N-methylpyrrolidinium chloride [Bu-Me-Pyrr(+)]Cl- from three of the main classes of ionic liquids were used in synthesis. Reactions using ionic liquids composed of the trihexyltetradecyl phosphonium cation [Th-Td-P+] and the anions; tetrafluoroborate [BF4 (-)], bis(trifluoro-methyl sulfonyl) imide [(Tf)(2)N-] and hexafluorophosphate [PF6 (-)] were also investigated.

  • 3730.
    Åkerstedt, Josefin
    et al.
    KTH, Skolan för kemivetenskap (CHE), Kemi, Oorganisk kemi (stängd 20110630).
    Gorlov, Mikhail
    KTH, Skolan för kemivetenskap (CHE), Kemi, Organisk kemi.
    Kloo, Lars
    KTH, Skolan för kemivetenskap (CHE), Kemi, Oorganisk kemi (stängd 20110630).
    Synthesis of Bi5[GaCl4]3 from room-temperature ionic liquid reaction mediaManuskript (preprint) (Annet vitenskapelig)
  • 3731.
    Åkerstedt, Josefin
    et al.
    KTH, Skolan för kemivetenskap (CHE), Kemi, Tillämpad fysikalisk kemi.
    Rosdahl, Jan
    KTH, Skolan för kemivetenskap (CHE), Kemi, Tillämpad fysikalisk kemi.
    Persson, Per
    Umeå University.
    Kloo, Lars
    KTH, Skolan för kemivetenskap (CHE), Kemi, Tillämpad fysikalisk kemi.
    Arsenic Clusters in Solution: An Experimental and A Priori Theoretical EXAFS StudyManuskript (preprint) (Annet vitenskapelig)
  • 3732.
    Åkerstedt, Josefin
    et al.
    KTH, Skolan för kemivetenskap (CHE), Kemi, Tillämpad fysikalisk kemi.
    Ruck, M.
    Kloo, Lars
    KTH, Skolan för kemivetenskap (CHE), Kemi, Tillämpad fysikalisk kemi.
    Long, J. R.
    Tungsten Chloride W3Cl10(CH3CN)3 fromRoom-temperature Synthesis in Ionic liquid using an Organic Co-solventManuskript (preprint) (Annet vitenskapelig)
  • 3733.
    Åkesson, Lovisa
    et al.
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Cellulär och klinisk proteomik. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Mahdessian, Diana
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Cellulär och klinisk proteomik.
    Gnann, Christian
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Cellulär och klinisk proteomik. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Thul, Peter
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Cellulär och klinisk proteomik.
    Lundberg, Emma
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Cellulär och klinisk proteomik.
    Spatial organization of the nucleolar proteome during mitosisManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    In the interphase cell, the membrane-less nucleoli are the sites of ribosome biogenesis. As part of the Human Protein Atlas we created an image catalogue comprising 1,314 nucleolar proteins using antibody-based proteomics. We show experimental evidence for 1,027 proteins localizing to the whole nucleoli and 287 to the fibrillar center or dense fibrillar component. We also propose a new sub-compartment located in the nucleoplasmic border denoted as nucleoli rim, comprising at least 131 proteins. As a step toward better understanding of nucleolar protein function during cell division, we additionally generated confocal images of 68 nucleolar proteins being recruited to the chromosomal periphery in mitosis. Thanks to the single cell resolution we were able to define three expression phenotypes among the mitotic chromosome proteins; early, intermediate and late recruitment suggesting phase specific functions. We also for the first time provide a proteome-wide confirmation that the nucleoli in general, but mitotic chromosome proteins in particular have a higher predicted intrinsic disorder level compared to cytoplasmic proteins, indicating that the perichromosomal layer indeed is a liquid-like layer.

  • 3734.
    Ånell, Rickard
    et al.
    KTH, Skolan för teknik och hälsa (STH), Naturvetenskap och biomedicin, Omgivningsfysiologi.
    Eiken, Ola
    KTH, Skolan för teknik och hälsa (STH), Naturvetenskap och biomedicin, Omgivningsfysiologi.
    Grönkvist, Mikael
    KTH, Skolan för teknik och hälsa (STH), Naturvetenskap och biomedicin, Omgivningsfysiologi.
    Sundblad, Patrik
    KTH, Skolan för teknik och hälsa (STH), Naturvetenskap och biomedicin, Omgivningsfysiologi.
    Gennser, Mikael
    KTH, Skolan för teknik och hälsa (STH), Naturvetenskap och biomedicin, Omgivningsfysiologi.
    Vaskulära gasbubblor hos jaktplanspiloter under olika flygprofiler2016Konferansepaper (Fagfellevurdert)
  • 3735.
    Ånell, Rickard
    et al.
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Medicinteknik och hälsosystem, Omgivningsfysiologi.
    Grönkvist, Mikael
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Medicinteknik och hälsosystem, Omgivningsfysiologi.
    Eiken, Ola
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Medicinteknik och hälsosystem, Omgivningsfysiologi.
    Gennser, Mikael
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Medicinteknik och hälsosystem, Omgivningsfysiologi.
    Is there a safe altitude to compress venous gas emboli after simulated high-altitude flying?2018Inngår i: Proceedings from Swedish Aeronautical Medical Associations Annual Scientific Meeting, 2018, 2018Konferansepaper (Fagfellevurdert)
  • 3736.
    Ånell, Rickard
    et al.
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Medicinteknik och hälsosystem, Omgivningsfysiologi. Swedish Aerospace Physiology Centre.
    Grönkvist, Mikael
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Medicinteknik och hälsosystem, Omgivningsfysiologi. Swedish Aerospace Physiology Centre.
    Eiken, Ola
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Medicinteknik och hälsosystem, Omgivningsfysiologi. Swedish Aerospace Physiology Centre.
    Gennser, Mikael
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Medicinteknik och hälsosystem, Omgivningsfysiologi. Swedish Aerospace Physiology Centre.
    Nitrogen Washout and Venous Gas Emboli During Sustained vs. Discontinuous High-Altitude Exposures2019Inngår i: Aerospace Medicine and Human Performance, ISSN 2375-6314, E-ISSN 2375-6322, Vol. 90, nr 6, s. 524-530Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    INTRODUCTION: The frequency of long-duration, high-altitude missions with fighter aircraft is increasing, which may increase the incidence of decompression sickness (DCS).The aim of the present study was to compare decompression stress during simulated sustained high-altitude flying vs. high-altitude flying interrupted by periods of moderate or marked cabin pressure increase. METHODS: The level of venous gas emboli (VGE) was assessed from cardiac ultrasound images using the 5-degree Eftedal-Brubakk scale. Nitrogen washout/uptake was measured using a closed circuit rebreather. Eight men were investigated in three conditions: one 80-min continuous exposure to a simulated cabin altitude of A) 24,000 ft, or four 20-min exposures to 24,000 ft interspersed by three 20-min intervals at 8) 20,000 ft or C) 900 ft. RESULTS: A and B induced marked and persistent VGE, With peak bubble scores of [median (range)]: A 2.5 (1-3); B: 3.5 (2-4). Peak VGE score was less in C [1.0(1-2),P < 0.01]. Condition A exhibitedan initially high and exponentially decaying rate of nitrogen washout. In C the washout rate was similar in each period at 24,000 ft, and the nitrogen uptake rate was similar during each 900-ft exposure. B exhibited nitrogen washout during each period at 24,000 ft and the initial period at 20,000 ft, but on average no washout or uptake during the last period at 20,000 ft. DISCUSSION: Intermittent reductions of cabin altitude from 24,000 to 20,000 ft do not appear to alleviate the DCS risk, presumably because the pressure increase is not sufficient to eliminate VGE. The nitrogen washout/uptake rate did not reflect DCS risk in the present exposures.

  • 3737.
    Ånell, Rickard
    et al.
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Medicinteknik och hälsosystem, Omgivningsfysiologi.
    Grönkvist, Mikael
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Medicinteknik och hälsosystem, Omgivningsfysiologi.
    Gennser, Mikael
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Medicinteknik och hälsosystem, Omgivningsfysiologi.
    Eiken, Ola
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Medicinteknik och hälsosystem, Omgivningsfysiologi.
    Evolution and Preservation of Venous Gas Emboli at Alternating High and Moderate Altitude Exposures2020Inngår i: Aerospace Medicine and Human Performance, ISSN 2375-6314, E-ISSN 2375-6322, Vol. 91, nr 1, s. 11-17Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    INTRODUCTION: The evolution and preservation of venous gas emboli (VGE), as markers of decompression stress, were investigated during alternating high- and moderate altitude exposures, thus, simulating a fighter aircraft high-altitude flight, interrupted by refueling excursions to lower altitudes. METHODS: Eight men served as subjects during three normoxic simulated altitude exposures: High = 90 min at 24,000 ft; High-Low = three x 30 min at 24,000 ft, interspersed by two 30-min intervals at 15,000 ft; Low = 90 min at 15,000 ft. VGE scores were assessed by cardiac ultrasound, using a 5-grade scale. Respiratory nitrogen exchange was measured continuously using a modified closed-circuit electronic rebreather. RESULTS: Both High and High-Low induced persistent VGE, with no inter-condition difference either at rest [median (range): High: 1 (0-3), High-Low: 2 (0-3)] or during unloaded knee-bends [High: 3 (1-4), High-Low: 3 (0-4)], whereas VGE was considerably less in Low, both at rest [0 (0-1)] and during knee-bends [0 (0-2)]. In High-Low, VGE decreased temporarily during the 15,000-ft excursions, but resumed pre-excursion values upon return to 24,000 ft. During the final descent to ground level, VGE were more persistent following High-Low than High. In both High and Low, nitrogen was continuously washed out at altitude, whereas in High-Low, the washout at 24,000 ft was interrupted by nitrogen uptake at 15,000 ft. DISCUSSION: In normoxic conditions, long-duration flying at a cabin altitude of 24,000 ft is associated with substantial VGE occurrence, which is not abolished by intermittent excursions to a cabin altitude of 15,000 ft.

  • 3738. Åneman, A.
    et al.
    Svensson, M.
    Broome, M.
    Karolinska Institutet.
    Biber, B.
    Petterson, A.
    Fandriks, L.
    Specific angiotensin II receptor blockage improves intestinal perfusion during graded hypovolemia in pigs2000Inngår i: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 28, nr 3, s. 818-823Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: To investigate the potential of specific angiotensin II subtype 1 (AT1) receptor blockade to modify the mesenteric hemodynamic response to acute hypovolemia and retransfusion. DESIGN: Prospective, randomized, controlled experimental study. SETTING: University-affiliated animal research laboratory. SUBJECTS: Fasted, anesthetized, ventilated, juvenile domestic pigs of both sexes. INTERVENTIONS: Acute, graded hypovolemia by 20% and 40% of the total estimated blood volume followed by retransfusion in control animals (CTRL; n = 10) and animals pretreated with the AT1 receptor blocker candesartan (CAND; n = 10). MEASUREMENTS AND MAIN RESULTS: Invasive monitoring of arterial and central venous blood pressures, cardiac output, portal venous blood flow, and jejunal mucosal blood flow. Blood gases were repeatedly analyzed to calculate oxygen delivery and consumption. Thirty minutes after each level of hypovolemia at 20% and 40%, cardiac output was decreased in CTRL animals from a baseline of 2.9 +/- 0.1 to 1.8 +/- 0.2 and 1.1 +/- 0.2 L/min, with no differences compared with CAND animals. Cardiac output was restored to 3.0 +/- 0.3 L/min 30 mins after retransfusion in CTRL animals, with no significant intergroup differences. Baseline portal venous blood flow (Q(MES)) and jejunal mucosal perfusion (PU(JEJ)) were greater in CAND animals compared with CTRL animals. During graded hypovolemia, CAND animals maintained Q(MES) and PU(JEJ) at significantly higher levels compared with CTRL animals, particularly after 40% hemorrhage (+221% and + 244%, respectively, relative to the mean values in CTRL animals). The same pattern was observed after retransfusion. Moreover, the calculated mesenteric critical oxygen delivery was significantly greater in CTRL animals (74 mL/min) compared with CAND animals (34 mL/min). No animals died in the CAND group, whereas four animals died during 40% hypovolemia or retransfusion in the CTRL group. CONCLUSIONS: Specific AT1 blockade before acute hypovolemia significantly ameliorated mesenteric and, in particular, jejunal mucosal hypoperfusion. In addition, cardiovascular stability was improved, and mortality in conjunction with acute hypovolemia and retransfusion could be completely avoided. These findings support a fundamental role of the renin-angiotensin system in the mesenteric response to acute hypovolemia and indicate a substantial interventional potential for candesartan in conjunction with circulatory stress.

  • 3739.
    Åsberg, M
    et al.
    Karolinska Institutet.
    Nygren, A
    Karolinska Institutet.
    Leopardi, Rosario
    Karolinska Institutet.
    Rylander, Gunnar
    Peterson, Ulla
    Wilczek, Lukas
    Karolinska Institutet.
    Källmén, Håkan
    Ekstedt, Mirjam
    Karolinska Institutet.
    Åkerstedt, Torbjörn
    Karolinska Institutet.
    Lekander, Mats
    Karolinska Institutet.
    Ekman, Rolf
    Novel biochemical markers of psychosocial stress in women2009Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 4, nr 1, s. e3590-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Prolonged psychosocial stress is a condition assessed through self-reports. Here we aimed to identify biochemical markers for screening and early intervention in women.

    METHODS: Plasma concentrations of interleukin (IL) 1-alpha, IL1-beta, IL-2, IL-4, IL-6, IL-8, IL-10, interferon-gamma (INF-gamma), tumor necrosis factor-alpha (TNF-alpha), monocyte chemotactic protein-1 (MCP-1), epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), thyroid stimulating hormone (TSH), total tri-iodothyronine (TT3), total thyroxine (TT4), prolactin, and testosterone were measured in: 195 women on long-term sick-leave for a stress-related affective disorder, 45 women at risk for professional burnout, and 84 healthy women.

    RESULTS: We found significantly increased levels of MCP-1, VEGF and EGF in women exposed to prolonged psychosocial stress. Statistical analysis indicates that they independently associate with a significant risk for being classified as ill.

    CONCLUSIONS: MCP-1, EGF, and VEGF are potential markers for screening and early intervention in women under prolonged psychosocial stress.

  • 3740. Åslund, M.
    et al.
    Cederström, Björn
    KTH, Tidigare Institutioner, Fysik.
    Lundqvist, M.
    Danielsson, Mats
    KTH, Tidigare Institutioner, Fysik.
    Scatter rejection in scanned multi-slit digital mammography2004Inngår i: Proceedings of SPIE - The International Society for Optical Engineering, 2004, nr 1, s. 478-487Konferansepaper (Fagfellevurdert)
    Abstract [en]

    Measurements and Monte Carlo simulations were used to investigate the scatter properties of a scanned multi-slit digital mammography system. Scatter to primary ratio (S/P) in the center of the image field was calculated for different thickness of breast equivalent material and different tube potentials. The simulated model also varied the angular acceptance, the number of slits and the distance between the slits of a dedicated scatter rejection device. In addition to the expected scatter from the breast equivalent material, scatter within the detector contributes to the S/P-ratio. The main part of the scatter is identified as coming from this process. Measured total 5/P-ratios below 3% are reported for breast range 3-8 cm. The scatter-DQE is used as figure-of-merit for comparison to other imaging geometries and scatter rejection schemes.

  • 3741.
    Åstrand, Mikael
    KTH, Skolan för bioteknologi (BIO), Proteinteknologi.
    Engineering strategies for ABD-derived affinity proteins for therapeutic and diagnostic applications2016Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Small stable protein domains are attractive scaffolds for engineering affinity proteins due to their high tolerance to mutagenesis without loosing structural integrity. The albuminbinding domain is a 5 kDa three-helix bundle derived from the bacterial receptor Protein G with low-nanomolar affinity to albumin. In this thesis, the albumin-binding domain is explored as a scaffold for engineering novel affinity proteins with the possible benefit of combining a prolonged serum half-life with specific targeting in a single small scaffold protein. Previously, a library was created by randomizing surface-exposed residues in order to engineer affinity to a new target antigen in addition to the inherent albumin affinity. Here, phage display selections were separately performed against the tumor antigens ERBB2 and ERBB3. The ERBB3 selection resulted in a panel of candidates that were found to have varying affinities to ERBB3 in the nanomolar range, while still retaining a high affinity to albumin. Further characterization concluded that the clones also competed for binding to ERBB3 with the natural activating ligand Heregulin. The selections against ERBB2 resulted in sub-nanomolar affinities to ERBB2 where the binding site was found to overlap with the antibody Trastuzumab. The binding sites on ABD to albumin and either target were found in both selections to be mutually exclusive, as increased concentrations of albumin reduced the level of binding to ERBB2 or ERBB3. An affinity-matured ERBB2 binder, denoted ADAPT6, which lacked affinity to albumin was evaluated as a radionuclide-labeled imaging tracer for diagnosing ERBB2-positive tumors. Biodistribution studies in mice showed a high renal uptake consistent with affinity proteins in the same size range and the injected ADAPT quickly localized to the implanted tumor. High contrast images could be generated and ERBB2-expressing tissue could be distinguished from normal tissue with high contrast, demonstrating the feasibility of the scaffold for use as diagnostic tool. In a fourth study, affinity maturation strategies using staphylococcal cell-surface display were evaluated by comparing two replicate selections and varying the stringency. A sub-nanomolar target concentration was concluded to be inappropriate for equilibrium selection as the resulting output was highly variable between replicates. In contrast, equilibrium sorting at higher concentrations followed by kinetic-focused off-rate selection resulted in high output overlap between attempts and a clear correlation between affinity and enrichment.

  • 3742.
    Örnberg, Andreas
    et al.
    KTH, Skolan för kemivetenskap (CHE), Kemi, Korrosionslära.
    Pan, Jinshan
    KTH, Skolan för kemivetenskap (CHE), Kemi, Korrosionslära.
    Leygraf, Christofer
    KTH, Skolan för kemivetenskap (CHE), Kemi, Korrosionslära.
    Electrochemical study of tantalum as substrate for pacemaker electrodesInngår i: Journal of the Electrochemical Society, ISSN 0013-4651, E-ISSN 1945-7111Artikkel i tidsskrift (Annet vitenskapelig)
  • 3743.
    Örtendahl, Monica
    KTH, Skolan för arkitektur och samhällsbyggnad (ABE), Transporter och samhällsekonomi (stängd 20110301), Säkerhetsforskning (stängd 20110301).
    Coping Mechanisms Actually and Hypothetically Used by Pregnant and Non-Pregnant Women in Quitting Smoking2008Inngår i: Journal of Addictive Diseases, ISSN 1055-0887, E-ISSN 1545-0848, Vol. 27, nr 4, s. 61-68Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The purpose of this article was to investigate how pregnant and non-pregnant women use various coping techniques when attempting to refrain from smoking. Eighty women with subgroups formed by the variables of pregnant/not pregnant and quitting/not quitting smoking were studied over a 2-week period. The general strategy was to follow smokers who had stated an intention to quit smoking. Smokers, pregnant and non-pregnant, who did not intend to quit were also followed with respect to the coping techniques they would hypothetically be using if they were trying to quit. Pregnant women used coping strategies more often than non-pregnant women. Differences found between pregnant and non-pregnant women were evenly distributed for behavioral and cognitive methods. The goal of becoming a non-smoker, especially during pregnancy, needs to be addressed to include psychological and physical factors. In these efforts, the framework introduced by the study involving a time-related approach could be useful.

  • 3744.
    Örtendahl, Monica
    KTH, Skolan för arkitektur och samhällsbyggnad (ABE), Transporter och samhällsekonomi (stängd 20110301), Säkerhetsforskning (stängd 20110301).
    Different time perspectives of the doctor and the patient reduce quality in health care2008Inngår i: Quality Management in Health Care, ISSN 1063-8628, E-ISSN 1550-5154, Vol. 17, nr 2, s. 136-139Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Time-related problems interfere with treatment decisions and evaluations in health care, both from the perspective of the doctor and from the perspective of the patient. The compliance level of the patient and subsequent evaluations in clinical practice might be affected by a discrepancy in the time perspective. Context factors related to time and health perspectives are relevant to clinical decisions and quality management. A summary of evaluation factors in quality management is presented: (a) the time perspective of the patient is different from the time perspective of the doctor, both in an objective and in a subjective manner; (b) disease chronicity chronic affects the perception of time; (c) assessments need to extend over a period sufficiently long for variations in a disease activity to be noticed; (d) there is variation both in time for an outcome to occur and in time span for that outcome; (e) the number of patients benefiting from certain drugs and variability over time is valuable information; (f) the outcome of a specified treatment could be estimated for different periods in a sequence; and (g) changes occur in judgments and decisions over time both for the doctor and for the patient.

  • 3745.
    Örtendahl, Monica
    KTH, Skolan för arkitektur och samhällsbyggnad (ABE), Transporter och samhällsekonomi (stängd 20110301), Säkerhetsforskning (stängd 20110301).
    Models based on value and probability in health improve shared decision making2008Inngår i: Journal of Evaluation In Clinical Practice, ISSN 1356-1294, E-ISSN 1365-2753, Vol. 14, nr 5, s. 714-717Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Rationale, aims and objectives Diagnostic reasoning and treatment decisions are a key competence of doctors. A model based on values and probability provides a conceptual framework for clinical judgments and decisions, and also facilitates the integration of clinical and biomedical knowledge into a diagnostic decision. Method Both value and probability are usually estimated values in clinical decision making. Therefore, model assumptions and parameter estimates should be continually assessed against data, and models should be revised accordingly. Introducing parameter estimates for both value and probability, which usually pertain in clinical work, gives the model labelled subjective expected utility. Estimated values and probabilities are involved sequentially for every step in the decision-making process. Results Introducing decision-analytic modelling gives a more complete picture of variables that influence the decisions carried out by the doctor and the patient. Conclusion A model revised for perceived values and probabilities by both the doctor and the patient could be used as a tool for engaging in a mutual and shared decision-making process in clinical work.

  • 3746.
    Örtendahl, Monica
    KTH, Skolan för arkitektur och samhällsbyggnad (ABE), Transporter och samhällsekonomi (stängd 20110301), Säkerhetsforskning (stängd 20110301).
    Predicting lapse when stopping smoking among pregnant and non-pregnant women2007Inngår i: Journal of Obstetrics and Gynaecology, ISSN 0144-3615, E-ISSN 1364-6893, Vol. 27, nr 2, s. 138-143Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    This study aimed to investigate factors predicting lapse among pregnant and non-pregnant women when trying to stop smoking. A total of 40 women, pregnant and non-pregnant, were investigated over a 2-week period when trying to stop smoking. One-quarter of the women lapsed every day. Not being pregnant was a significant predictor for the occurrence of any lapse during the time period, whereas age, number of years of smoking, number of earlier attempts to stop smoking, and number of cigarettes smoked per day did not predict lapse. There was a four times higher risk for lapse in non-pregnant compared with pregnant women. Being pregnant gives an opportunity to help stop smoking with a considerably lower risk of lapse compared with non-pregnant women.

  • 3747.
    Örtendahl, Monica
    KTH, Skolan för arkitektur och samhällsbyggnad (ABE), Transporter och samhällsekonomi (stängd 20110301), Säkerhetsforskning (stängd 20110301).
    Shared decision-making based on different features of risk in the context of diabetes mellitus and rheumatoid arthritis2007Inngår i: Therapeutics and Clinical Risk Management, ISSN 1176-6336, E-ISSN 1178-203X, Vol. 3, nr 6, s. 1175-1180Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    There is an increased awareness about patients' involvement in the clinical decision process where uncertainty is an unavoidable condition. The impact of psychological factors like risk aversion, risk aversion and time, asymmetry in risk aversion, and risk and control on shared decision-making is discussed. In addition to differences in risk estimates, doctors and patients may exhibit a difference in perception of time perspectives, and losses versus gains. A summary of valuation factors in shared decision-making is presented: (a) the doctors tend to follow expected value combinations more closely, while the patient is more risk aversive; (b) unwillingness to take risks increases for rare outcomes; (c) there is an increased tendency to take risks with delayed outcomes of the decisions; (d) the doctor is generally well informed about risk and time aspects for different diseases, whereas this might not always be the case with the patient; (e) rheumatoid arthritis and diabetes mellitus are chronic diseases, and both create a vulnerability to a variety of complications over time; (f) rheumatoid arthritis demands different combinations of treatments sequentially over time, whereas diabetes mellitus is treated with insulin; (g) many diseases, like rheumatoid arthritis and diabetes mellitus, are not completely affected by control, as the disease may constantly progress.

  • 3748.
    Örtendahl, Monica
    et al.
    KTH, Skolan för arkitektur och samhällsbyggnad (ABE), Transporter och samhällsekonomi (stängd 20110301), Säkerhetsforskning (stängd 20110301).
    Näsman, Per
    KTH, Skolan för arkitektur och samhällsbyggnad (ABE), Transporter och samhällsekonomi (stängd 20110301), Säkerhetsforskning (stängd 20110301).
    Factors Affecting Continuation of Smoking by Pregnant and Non-pregnant Women2009Inngår i: Substance Abuse, ISSN 0889-7077, E-ISSN 1573-6733, Vol. 30, nr 2, s. 150-157Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The objective of this study was to test a framework based upon the value and the probability of outcomes related to smoking. Over a 2-week period, 80 women were asked to perform judgments of value and probability of the outcome for smoking-related consequences. Subgroups were formed by the two variables of pregnancy and intent to quit smoking. Judgments were performed given the conditions of quitting and not quitting smoking. The intent to quit or not quit smoking had an impact on expected utility of smoking. Moreover, there was a difference between expected utility given the conditions of not quitting smoking and quitting smoking. A framework based upon values and beliefs appears to be useful in describing the addictive behavior of smoking and can be applied in developing smoking-cessation education.

  • 3749.
    Örtendahl, Monica
    et al.
    KTH, Skolan för arkitektur och samhällsbyggnad (ABE), Transporter och samhällsekonomi, Säkerhetsforskning.
    Näsman, Per
    KTH, Skolan för arkitektur och samhällsbyggnad (ABE), Transporter och samhällsekonomi, Säkerhetsforskning.
    Judgments of Risk for Consequences of Continuing or Quitting Smoking: A Study of Pregnant and Nonpregnant Women Intending and not Intending to Quit2008Inngår i: American journal of drug and alcohol abuse, ISSN 0095-2990, E-ISSN 1097-9891, Vol. 34, nr 2, s. 225-233Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

     Objectives: To study perceived smoking-related consequences of continuing and of quitting smoking. Methods: Eighty women, with subgroups formed by pregnant/nonpregnant women and trying/not trying to quit smoking, performed judgments of the probability for consequences to occur given the conditions of continuing or quitting smoking. Results: For both the pregnant and nonpregnant women, the probability that consequences will occur was rated as less likely given the condition of quitting smoking. The condition of quitting had its greatest effect on the probability that somatic consequences would occur. Conclusion: Consequences of smoking for somatic health should be stressed in health promotion, especially to pregnant women.

  • 3750.
    Örtendahl, Monica
    et al.
    KTH, Skolan för arkitektur och samhällsbyggnad (ABE), Transporter och samhällsekonomi, Säkerhetsforskning.
    Näsman, Per
    KTH, Skolan för arkitektur och samhällsbyggnad (ABE), Transporter och samhällsekonomi, Säkerhetsforskning.
     Perception of smoking-related health consequences among pregnant and non-pregnant women2007Inngår i: American Journal on Addictions, ISSN 1055-0496, E-ISSN 1521-0391, Vol. 16, nr 6, s. 521-527Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The objective was to examine the perception of smoking-related health consequences and its relationship to pregnancy and intent to quit. Over a two-week period, pregnant and non-pregnant women, intending and not intending to quit smoking, rated the probability for smoking-related health consequences to occur, given continuing to smoke and quitting smoking. Pregnant women who did not intend to quit smoking exhibited the lowest estimated probability for the smoking-related health consequences to occur if they continued smoking. For all women, there was a statistically significant estimated effect of quitting smoking. Renewed attention needs to be given to perceptions of health risks of smoking, especially among pregnant women.

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