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  • 1051. Wågström, Elle
    et al.
    Johnson, Jonas
    KTH, School of Technology and Health (STH), Medical Engineering.
    Ferm-Widlund, Kjerstin
    Elmstedt, Nina
    KTH, School of Technology and Health (STH), Medical Engineering.
    Liuba, Karina
    Lind, Britta
    KTH, School of Technology and Health (STH), Medical Engineering.
    Brodin, Lars-Åke
    KTH, School of Technology and Health (STH), Medical Engineering.
    Westgren, Magnus
    The Cardiac State Diagram as a novel approach for evaluation of phases of the cardiac cycle in asfyxiated fetal lambs2012In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 91, p. 144-144Article in journal (Other academic)
  • 1052.
    Wållberg, Helena
    et al.
    KTH, School of Biotechnology (BIO), Molecular Biotechnology.
    Orlova, Anna
    Altai, Mohammed
    Hosseinimehr, Seyed Jalal
    Widström, Charles
    Malmberg, Jennie
    Ståhl, Stefan
    KTH, School of Biotechnology (BIO), Molecular Biotechnology.
    Tolmachev, Vladimir
    Molecular Design and Optimization of Tc-99m-Labeled Recombinant Affibody Molecules Improves Their Biodistribution and Imaging Properties2011In: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667, Vol. 52, no 3, p. 461-469Article in journal (Refereed)
    Abstract [en]

    Affibody molecules are a recently developed class of targeting proteins based on a nonimmunoglobulin scaffold. The small size (7 kDa) and subnanomolar affinity of Affibody molecules enables high-contrast imaging of tumor-associated molecular targets, particularly human epidermal growth factor receptor type 2 (HER2). Tc-99m as a label offers advantages in clinical practice, and earlier studies demonstrated that Tc-99m-labeled recombinant Affibody molecules with a C-terminal cysteine could be used for HER2 imaging. However, the renal retention of radioactivity exceeded tumor uptake, which might complicate imaging of metastases in the lumbar region. The aim of this study was to develop an agent with low renal uptake and preserved tumor targeting. Methods: A series of recombinant derivatives of the HER2-binding Z(HER2:342) Affibody molecule with a C-terminal chelating sequence, -GXXC (X denoting glycine, serine, lysine, or glutamate), was designed. The constructs were labeled with Tc-99m and evaluated in vitro and in vivo. Results: All variants were stably labeled with Tc-99m, with preserved capacity to bind specifically to HER2-expressing cells in vitro and in vivo. The composition of the chelating sequence had a clear influence on the cellular processing and biodistribution properties of the Affibody molecules. The best variant, Tc-99m-Z(HER2:V2), with the C-terminal chelating sequence -GGGC, provided the lowest radioactivity retention in all normal organs and tissues including the kidneys. Tc-99m-Z(HER2:V2) displayed high uptake of radioactivity in HER2-expressing xenografts, 22.6 +/- 4.0 and 7.7 +/- 1.5 percentage injected activity per gram of tissue at 4 h after injection in SKOV-3 (high HER2 expression) and DU-145 (low HER2 expression) tumors, respectively. In both models, the tumor uptake exceeded the renal uptake. Conclusion: These results demonstrate that the biodistribution properties of recombinant Tc-99m-labeled Affibody molecules can be optimized by modification of the C-terminal cysteine-containing chelating sequence. Tc-99m-Z(HER2:V2) is a promising candidate for further development as a diagnostic radiopharmaceutical for imaging of HER2-expressing tumors. These results may be useful for the development of imaging agents based on other Affibody molecules and, hopefully, other scaffolds.

  • 1053. Xia, Yang
    et al.
    Stilbs, Peter
    KTH, School of Chemical Science and Engineering (CHE), Chemistry, Applied Physical Chemistry.
    The First Study of Cartilage by Magnetic Resonance: A Historical Account2016In: Cartilage, ISSN 1947-6035, E-ISSN 1947-6043, Vol. 7, no 4, p. 293-297Article in journal (Refereed)
    Abstract [en]

    Objective. To recap the historical journey leading to the first cartilage research article using nuclear magnetic resonance (NMR), published in 1955 by 2 Swedish researchers, Erik Odeblad and Gunnar Lindstrom. Design. Extensive Internet search utilizing both English and Swedish websites, and reading the dissertations available at the Royal Institute of Technology (Stockholm, Sweden) and via interlibrary loans at Oakland University (Michigan, USA). Results. Using a primitive NMR instrument that Lindstrom built for his graduate research at the Nobel Institute for Physics (Stockholm, Sweden), Odeblad and Lindstrom studied the characteristics of the NMR signal in calf cartilage. The authors wrote, "In cartilage and fibrous tissue, in which the proton signals probably arise from highly viscous water with short spin-lattice relaxation time, the signals were also larger than would correspond to the water content." The authors speculated the signal differences between water and biological tissues could be attributed to the absorption and organization of the water molecules to the proteins in the tissue, which was remarkably accurate. Conclusions. It is quite certain that Odeblad and Lindstrom published the first biomedical study using NMR in 1955. In this article, cartilage and a number of other biological tissues were examined for the first time using NMR.

  • 1054.
    Xie, Meng
    et al.
    Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden..
    Gol'din, Pavel
    Stockholm Univ, Stockholm, Sweden..
    Estsfa, Jordi
    Uppsala Univ, Dept Organismal Biol, Uppsala, Sweden..
    Li, Lei
    Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden..
    Linares Arregui, Irene
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.).
    Gasser, T. Christian
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.).
    Medvedeva, Ekaterina
    Sechenov Med Univ, Moscow, Russia..
    Svetlana, Kotova
    Sechenov Med Univ, Moscow, Russia..
    Timashev, Peter
    Sechenov Med Univ, Moscow, Russia..
    Adameyko, Igor
    Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden..
    Eriksson, Anders
    KTH, School of Engineering Sciences (SCI), Mechanics.
    Sanchez, Sophie
    Uppsala Univ, Dept Organismal Biol, Uppsala, Sweden..
    Chagin, Andrei
    Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden..
    Evolutional Separation of Epiphyseal and Articular Cartilage is a Bone Adaptation to Terrestrial Growth2017In: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 32, p. S328-S328Article in journal (Other academic)
  • 1055.
    Xu, Cheng
    KTH, School of Engineering Sciences (SCI), Physics, Medical Imaging.
    A Segmented Silicon Strip Detector for Photon-Counting Spectral Computed Tomography2012Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Spectral computed tomography with energy-resolving detectors has a potential to improve the detectability of images and correspondingly reduce the radiation dose to patients by extracting and properly using the energy information in the broad x-ray spectrum. A silicon photon-counting detector has been developed for spectral CT and it has successfully solved the problem of high photon flux in clinical CT applications by adopting the segmented detector structure and operating the detector in edge-on geometry. The detector was evaluated by both the simulation and measurements.

    The effects of energy loss and charge sharing on the energy response of this segmented silicon strip detector with different pixel sizes were investigated by Monte Carlo simulation and a comparison to pixelated CdTe detectors is presented. The validity of spherical approximations of initial charge cloud shape in silicon detectors was evaluated and a more accurate statistical model has been proposed.

    A photon-counting energy-resolving application specific integrated circuit (ASIC) developed for spectral CT was characterized extensively by electrical pulses, pulsed laser and real x-ray photons from both the synchrotron and an x-ray tube. It has been demonstrated that the ASIC performs as designed. A noise level of 1.09 keV RMS has been measured and a threshold dispersion of 0.89 keV RMS has been determined. The count rate performance of the ASIC in terms of count loss and energy resolution was evaluated by real x-rays and promising results have been obtained.

    The segmented silicon strip detector was evaluated using synchrotron radiation. An energy resolution of 16.1% has been determined with 22 keV photons in the lowest flux limit, which deteriorates to 21.5% at an input count rate of 100 Mcps mm−2. The fraction of charge shared events has been estimated and found to be 11.1% for 22 keV and 15.3% for 30 keV. A lower fraction of charge shared events and an improved energy resolution can be expected by applying a higher bias voltage to the detector.

    Download full text (pdf)
    PhD_thesis_ChengXu
  • 1056. Yamada, Takashi
    et al.
    Bruton, Joseph D.
    Place, Nicolas
    Zhang, Shi-jin
    Kosterina, Natalia
    KTH, School of Engineering Sciences (SCI), Mechanics, Structural Mechanics.
    Harris, Helena E.
    Östberg, Therese
    Grundtman, Cecilia
    Glenmark, Birgitta
    Westerblad, Hakan
    IMPAIRED MYOFIBRILLAR FUNCTION IN SOLEUS MUSCLE OF MICE WITH COLLAGEN-INDUCED ARTHRITIS2009In: JOURNAL OF PHYSIOLOGICAL SCIENCES, ISSN 1880-6546, Vol. 59, p. 215-215Article in journal (Other academic)
  • 1057. Yamada, Takashi
    et al.
    Place, Nicolas
    Kosterina, Natalia
    KTH, School of Engineering Sciences (SCI), Mechanics, Structural Mechanics.
    Östberg, Therese
    Zhang, Shi-Jin
    Grundtman, Cecilia
    Erlandsson-Harris, Helena
    Lundberg, Ingrid E.
    Glenmark, Birgitta
    Bruton, Joseph D.
    Westerblad, Hakan
    Impaired Myofibrillar Function in the Soleus Muscle of Mice With Collagen-Induced Arthritis2009In: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 60, no 11, p. 3280-3289Article in journal (Refereed)
    Abstract [en]

    Objective. Progressive muscle weakness is a common feature in patients with rheumatoid arthritis (RA). However, little is known about whether the intrinsic contractile properties of muscle fibers are affected in RA. This study was undertaken to investigate muscle contractility and the myoplasmic free Ca2+ concentration ([Ca2+](i)) in the soleus, a major postural muscle, in mice with collagen-induced arthritis (CIA). Methods. Muscle contractility and [Ca2+](i) were assessed in whole muscle and intact single-fiber preparations, respectively. The underlying mechanisms of contractile dysfunction were assessed by investigating redox modifications using Western blotting and antibodies against nitric oxide synthase (NOS), superoxide dismutase (SOD), 3-nitrotyrosine (3-NT), carbonyl, malondialdehyde (MDA), and S-nitrosocysteine (SNO-Cys). Results. The tetanic force per cross-sectional area was markedly decreased in the soleus muscle of mice with CIA, and the change was not due to a decrease in the amplitude of [Ca2+](i) transients. The reduction in force production was accompanied by slowing of the twitch contraction and relaxation and a decrease in the maximum shortening velocity. Immunoblot analyses showed a marked increase in neuronal NOS expression but not in inducible or endothelial NOS expression, which, together with the observed decrease in SOD2 expression, favors peroxynitrite formation. These changes were accompanied by increased 3-NT, carbonyl, and MDA adducts content in myofibrillar proteins from the muscles of mice with CIA. Moreover, there was a significant increase in SNO-Cys content in myosin heavy-chain and troponin I myofibrillar proteins from the soleus muscle of mice with CIA. Conclusion. These findings show impaired contractile function in the soleus muscle of mice with CIA and suggest that this abnormality is due to peroxynitrite-induced modifications in myofibrillar proteins.

  • 1058. Yao, Y.
    et al.
    Bornefalk, Hans
    KTH, School of Engineering Sciences (SCI), Physics, Physics of Medical Imaging.
    Hsieh, S. S.
    Danielsson, Mats
    KTH, School of Engineering Sciences (SCI), Physics, Physics of Medical Imaging.
    Pelc, N. J.
    Use of depth information from in-depth photon counting detectors for x-ray spectral imaging: A preliminary simulation study2014In: Medical Imaging 2014: Physics of Medical Imaging, SPIE - International Society for Optical Engineering, 2014, p. 90333E-Conference paper (Refereed)
    Abstract [en]

    Purpose: Photon counting x-ray detectors (PCXD) may improve dose-efficiency but are hampered by limited count rate. They generally have imperfect energy response. Multi-layer ("in-depth") detectors have been proposed to enable higher count rates but the potential benefit of the depth information has not been explored. We conducted a simulation study to compare in-depth detectors against single layer detectors composed of common materials. Both photon counting and energy integrating modes were studied. Methods: Polyenergetic transmissions were simulated through 25cm of water and 1cm of calcium. For PCXD composed of Si, GaAs or CdTe a 120kVp spectrum was used. For energy integrating x-ray detectors (EIXD) made from GaAs, CdTe or CsI, spectral imaging was done using 80 and 140kVp and matched dose. Semi-ideal and phenomenological energy response models were used. To compare these detectors, we computed the Cramér-Rao lower bound (CRLB) of the variance of basis material estimates. Results: For PCXDs with perfect energy response, depth data provides no additional information. For PCXDs with imperfect energy response and for EIXDs the improvement can be significant. E.g., for a CdTe PCXD with realistic energy response, depth information can reduce the variance by 50%. The improvement depends on the x-ray spectrum. For a semi-ideal Si detector and a narrow x-ray spectrum the depth information has minimal advantage. For EIXD, the in-depth detector has consistent variance reduction (15% and 17%19% for water and calcium, respectively). Conclusions: Depth information is beneficial to spectral imaging for both PCXD and EIXD. The improvement depends critically on the detector energy response.

  • 1059.
    Yao, Yuan
    et al.
    Stanford Univ, Dept Radiol, Stanford, CA 94305 USA. Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA..
    Bornefalk, Hans
    KTH, School of Engineering Sciences (SCI), Physics.
    Hsieh, Scott S.
    Danielsson, Mats
    KTH, School of Engineering Sciences (SCI), Physics, Physics of Medical Imaging. Royal Inst Technol, Dept Phys, Stockholm, Sweden..
    Pelc, Norbert J.
    UTILIZATION OF IN-DEPTH PHOTON COUNTING DETECTORS TOWARDS X-RAY SPECTRAL IMAGING: THE BENEFITS FROM THE DEPTH INFORMATION2014In: 2014 IEEE 11th International Symposium on Biomedical Imaging (ISBI), IEEE , 2014, p. 1156-1159Conference paper (Refereed)
    Abstract [en]

    The in-depth photon counting x-ray detector (PCXD) is a multi-layer detector arrangement which has been introduced to tackle photon count rate limitations of current systems. The capability of resolving photon detections along the detector's depth direction enables multiple measurements in a single scan with energy information that could be potentially utilized for x-ray spectral imaging. The benefit of this depth information has not been explored. We conducted a simulation study to evaluate the performance of in-depth PCXDs for dual material decomposition and compared it against single layer detectors. Common semiconductor materials (Si, GaAs and CdTe) were assessed, with imperfect energy response modeled. We demonstrate that depth information is useful if spectral distortion is present. The benefits depend on how the detector is segmented in the depth direction.

  • 1060. Ye, Fei
    et al.
    Zhao, Ying
    Ei-Sayed, Ramy
    Muhammed, Mamoun
    KTH. Alexandria University, Egypt.
    Hassan, Moustapha
    Advances in nanotechnology for cancer biomarkers2018In: Nano Today, ISSN 1748-0132, E-ISSN 1878-044X, Vol. 18, p. 103-123Article in journal (Refereed)
    Abstract [en]

    Cancer biomarkers with high selectivity, specificity and reproducibility play essential role in diagnosis, prognosis and prediction of treatment efficacy in cancer patients. However, the current biomarker assays used in clinics could be improved due to low sensitivity and specificity. Nanoparticle-based assays are emerging as an upcoming approach, providing ultra-high sensitivity and specificity in cancer biomarker detection. The current survey presents an overview of strategies used in the development and integration of nanoparticles for cancer biomarker detection, including mass spectrometry, optical and electrical detection methods. Moreover, we discuss the future trends in the field in correlation to new approaches from fundamental and practical standpoints.

  • 1061.
    Yoosuf, Niyaz
    et al.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab. Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, 141 83, Sweden.
    Fernandez Navarro, Jose
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Salmén, Fredrik
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab. Hubrecht Institute-KNAW (Royal Netherlands Academy of Arts and Sciences), University Medical Center Utrecht, Cancer Genomics Netherlands, Utrecht, Netherlands.
    Ståhl, Patrik
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Daub, C. O.
    Identification and transfer of spatial transcriptomics signatures for cancer diagnosis2020In: Breast Cancer Research, ISSN 1465-5411, E-ISSN 1465-542X, Vol. 22, no 1, article id 6Article in journal (Refereed)
    Abstract [en]

    Background: Distinguishing ductal carcinoma in situ (DCIS) from invasive ductal carcinoma (IDC) regions in clinical biopsies constitutes a diagnostic challenge. Spatial transcriptomics (ST) is an in situ capturing method, which allows quantification and visualization of transcriptomes in individual tissue sections. In the past, studies have shown that breast cancer samples can be used to study their transcriptomes with spatial resolution in individual tissue sections. Previously, supervised machine learning methods were used in clinical studies to predict the clinical outcomes for cancer types. Methods: We used four publicly available ST breast cancer datasets from breast tissue sections annotated by pathologists as non-malignant, DCIS, or IDC. We trained and tested a machine learning method (support vector machine) based on the expert annotation as well as based on automatic selection of cell types by their transcriptome profiles. Results: We identified expression signatures for expert annotated regions (non-malignant, DCIS, and IDC) and build machine learning models. Classification results for 798 expression signature transcripts showed high coincidence with the expert pathologist annotation for DCIS (100%) and IDC (96%). Extending our analysis to include all 25,179 expressed transcripts resulted in an accuracy of 99% for DCIS and 98% for IDC. Further, classification based on an automatically identified expression signature covering all ST spots of tissue sections resulted in prediction accuracy of 95% for DCIS and 91% for IDC. Conclusions: This concept study suggest that the ST signatures learned from expert selected breast cancer tissue sections can be used to identify breast cancer regions in whole tissue sections including regions not trained on. Furthermore, the identified expression signatures can classify cancer regions in tissue sections not used for training with high accuracy. Expert-generated but even automatically generated cancer signatures from ST data might be able to classify breast cancer regions and provide clinical decision support for pathologists in the future.

  • 1062.
    Yu, Sicong
    et al.
    KTH, School of Technology and Health (STH).
    Hamid Muhammad, Hamed
    KTH, School of Technology and Health (STH), Health Systems Engineering, Systems Safety and Management.
    Denoising of SPECT-image sinogram-data before reconstruction2014In: WMSCI 2014 - 18th World Multi-Conference on Systemics, Cybernetics and Informatics, Proceedings, 2014, Vol. 1, p. 202-206Conference paper (Refereed)
    Abstract [en]

    Nuclear medicine images have low signal-to-noise ratio (SNR) due to several physical limitations which degrade the image quality considerably. In this study, the Gaussian filter and the patch confidence Gaussian filter (PCG) were used to improve the image quality for Single Photon Emission Computed Tomography (SPECT). The new approach applies these filtering methods on the acquired 2D-projections before reconstructing the image. The new approach was evaluated on a SPECT dataset and the performance was compared with several conventional methods presented in the literature.

  • 1063. Yu, Xue Qin
    et al.
    Luo, Qingwei
    Smith, David P.
    Clements, Mark S.
    KTH, School of Engineering Sciences (SCI), Mechanics. KTH, Centres, SeRC - Swedish e-Science Research Centre.
    O'Connell, Dianne L.
    Prostate cancer prevalence in New South Wales Australia: A population-based study2015In: Cancer Epidemiology, ISSN 1877-7821, E-ISSN 1877-783X, Vol. 39, no 1, p. 29-36Article in journal (Refereed)
    Abstract [en]

    Background: Information on the current and future numbers of Australian men living with prostate cancer is limited. We describe a method for estimating complete prevalence of prostate cancer to provide a measure of the burden of prostate cancer in Australia. Methods: Prostate cancer data from the New South Wales (NSW) Central Cancer Registry were used with PIAMOD (Prevalence and Incidence Analysis MODel) software to estimate future prostate cancer prevalence in NSW. We first fitted parametric incidence and survival models then used the modelled incidence and survival estimates to calculate complete prevalence. The estimated and projected prevalence incorporate past observed trends and take into account different assumptions about future survival trends. These models were validated against observed prevalence from the counting method. Results: Based on data for 1996-2007, the number of men living with prostate cancer in NSW was estimated to rise by 59% to 73%, from 38,322 in 2007 to 60,910-66,160 in 2017. The increasing incidence rates and the ageing population were the major contributors to this estimated increase. Validation suggested that these projections were reasonable, as the estimated prevalence in 1996-2007 was in good agreement with the corresponding prevalence calculated using the direct counting method, and the incidence models were supported by the recent data on prostate-specific antigen testing. Conclusions: As the number of men living with prostate cancer is expected to increase dramatically in the next decade in Australia, representing a significant challenge to the health system, careful planning and development of a healthcare system able to respond to this increased demand is required. These projections are useful for addressing the challenge in meeting the cancer care needs of men with prostate cancer.

  • 1064. Yu, Xue Qin
    et al.
    Luo, Qingwei
    Smith, David P.
    Clements, Mark S.
    KTH, School of Engineering Sciences (SCI), Mechanics. KTH, Centres, SeRC - Swedish e-Science Research Centre.
    Patel, Manish I.
    O'Connell, Dianne L.
    Phase of care prevalence for prostate cancer in New South Wales, Australia: A population-based modelling study2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 2, article id e0171013Article in journal (Refereed)
    Abstract [en]

    Objective To develop a method for estimating the future numbers of prostate cancer survivors requiring different levels of care. Design, setting and participants Analysis of population-based cancer registry data for prostate cancer cases (aged 18-84 years) diagnosed in 1996-2007, and a linked dataset with hospital admission data for men with prostate cancer diagnosed during 2005-2007 in New South Wales (NSW), Australia. Methods Cancer registry data (1996-2007) were used to project complete prostate cancer prevalence in NSW, Australia for 2008-2017, and treatment information from hospital records (2005-2007) was used to estimate the inpatient care needs during the first year after diagnosis. The projected complete prevalence was divided into care needs-based groups. We first divided the cohort into two groups based on patient's age (<75 and 75-84 years). The younger cohort was further divided into initial care and monitoring phases. Cause of death data were used as a proxy for patients requiring last year of life prostate cancer care. Finally, episode data were used to estimate the future number of cases with metastatic progression. Results Of the estimated total of 60,910 men with a previous diagnosis of prostate cancer in 2017, the largest groups will be older patients (52.0%) and younger men who require monitoring (42.5%). If current treatment patterns continue, in the first year post-diagnosis 41% (1380) of patients (<75 years) will have a radical prostatectomy, and 52.6% (1752) will be likely to have either active surveillance, external beam radiotherapy or androgen deprivation therapy. About 3% will require care for subsequent metastases, and 1288 men with prostate cancer are likely to die from the disease in 2017. Conclusions This method extends the application of routinely collected population-based data, and can contribute much to the knowledge of the number of men with prostate cancer and their health care requirements. This could be of significant use in planning future cancer care services and facilities in Australia.

  • 1065.
    Yu, Yang
    et al.
    Karolinska Inst, Ctr Alzheimer Res, Div Neurogeriatr, Dept Neurobiol Care Sci & Soc, Huddinge, Sweden..
    Jans, Daniel C.
    KTH, School of Engineering Sciences (SCI), Applied Physics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Winblad, Bengt
    Karolinska Inst, Ctr Alzheimer Res, Div Neurogeriatr, Dept Neurobiol Care Sci & Soc, Huddinge, Sweden..
    Tjernberg, Lars O.
    Karolinska Inst, Ctr Alzheimer Res, Div Neurogeriatr, Dept Neurobiol Care Sci & Soc, Huddinge, Sweden..
    Schedin-Weiss, Sophia
    Karolinska Inst, Ctr Alzheimer Res, Div Neurogeriatr, Dept Neurobiol Care Sci & Soc, Huddinge, Sweden..
    Neuronal A beta 42 is enriched in small vesicles at the presynaptic side of synapses2018In: LIFE SCIENCE ALLIANCE, ISSN 2575-1077, Vol. 1, no 3, article id e201800028Article in journal (Refereed)
    Abstract [en]

    The amyloid beta-peptide (A beta) is a physiological ubiquitously expressed peptide suggested to be involved in synaptic function, long-term potentiation, and memory function. The 42 amino acid-long variant (A beta 42) forms neurotoxic oligomers and amyloid plaques and plays a key role in the loss of synapses and other pathogenic events of Alzheimer disease. Still, the exact localization of A beta 42 in neurons and at synapses has not been reported. Here, we used super-resolution microscopy and show that A beta 42 was present in small vesicles in presynaptic compartments, but not in postsynaptic compartments, in the neurites of hippocampal neurons. Some of these vesicles appeared to lack synaptophysin, indicating that they differ from the synaptic vesicles responsible for neurotransmitter release. The A beta 42-containing vesicles existed in presynapses connected to stubby spines and mushroom spines, and were also present in immature presynapses. These vesicleswere scarce inother parts of the neurites, where A beta 42 was instead present in large, around 200-600 nm, vesicular structures. Three-dimensional super-resolution microscopy confirmed that A beta 42 was present in the presynapse and absent in the postsynapse.

  • 1066.
    Yveborg, Moa
    et al.
    KTH, School of Engineering Sciences (SCI), Physics, Medical Imaging.
    Danielsson, Mats
    KTH, School of Engineering Sciences (SCI), Physics, Medical Imaging.
    Bornefalk, Hans
    KTH, School of Engineering Sciences (SCI), Physics, Medical Imaging.
    Performance evaluation of a sub-millimetre spectrally resolved CT system on high- and low-frequency imaging tasks: a simulation2012In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 57, no 8, p. 2373-2391Article in journal (Refereed)
    Abstract [en]

    We are developing a photon-counting silicon strip detector with 0.4 x 0.5 mm(2) detector elements for clinical CT applications. Except for the limited detection efficiency of approximately 0.8 for a spectrum of 80 kVp, the largest discrepancies from ideal spectral behaviour have been shown to be Compton interactions in the detector and electronic noise. Using the framework of cascaded system analysis, we reconstruct the 3D MTF and NPS of a silicon strip detector including the influence of scatter and charge sharing inside the detector. We compare the reconstructed noise and signal characteristics with a reconstructed 3D MTF and NPS of an ideal energy-integrating detector system with unity detection efficiency, no scatter or charge sharing inside the detector, unity presampling MTF and 1 x 1 mm(2) detector elements. The comparison is done by calculating the dose-normalized detectability index for some clinically relevant imaging tasks and spectra. This work demonstrates that although the detection efficiency of the silicon detector rapidly drops for the acceleration voltages encountered in clinical computed tomography practice, and despite the high fraction of Compton interactions due to the low atomic number, silicon detectors can perform on a par with ideal energy-integrating detectors for routine imaging tasks containing low-frequency components. For imaging tasks containing high-frequency components, the proposed silicon detector system can perform approximately 1.1-1.3 times better than a fully ideal energy-integrating system.

  • 1067.
    Zandian, Arash
    et al.
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Wingård, L.
    Nilsson, H.
    Sjöstedt, E.
    Johansson, D. X.
    Just, David
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Hellström, Cecilia
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Uhlén, Mathias
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Schwenk, Jochen M.
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Häggmark-Månberg, Anna
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Norbeck, O.
    Owe-Larsson, B.
    Nilsson, Peter
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Persson, M. A. A.
    Untargeted screening for novel autoantibodies with prognostic value in first-episode psychosis2017In: Translational Psychiatry, ISSN 2158-3188, E-ISSN 2158-3188, Vol. 7, article id e1177Article in journal (Refereed)
    Abstract [en]

    Immunological and inflammatory reactions have been suggested to have a role in the development of schizophrenia, a hypothesis that has recently been supported by genetic data. The aim of our study was to perform an unbiased search for autoantibodies in patients with a first psychotic episode, and to explore the association between any seroreactivity and the development of a Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) disorder characterized by chronic or relapsing psychotic symptoms. We collected plasma samples from 53 patients when they were treated for their first-episode psychosis, and 41 non-psychotic controls, after which the patients were followed for a mean duration of 7 years. Thirty patients were diagnosed with schizophrenia, delusional disorder, schizoaffective disorder, bipolar disorder or a long-term unspecified nonorganic psychosis during follow-up, whereas 23 patients achieved complete remission. At the end of follow-up, plasma samples were analyzed for IgG reactivity to 2304 fragments of human proteins using a multiplexed affinity proteomic technique. Eight patient samples showed autoreactivity to the N-terminal fragment of the PAGE (P antigen) protein family (PAGE2B/PAGE2/PAGE5), whereas no such autoreactivity was seen among the controls. PAGE autoreactivity was associated with a significantly increased risk of being diagnosed with schizophrenia during follow-up (odds ratio 6.7, relative risk 4.6). An immunohistochemistry analysis using antisera raised against the N-terminal fragment stained an unknown extracellular target in human cortical brain tissue. Our findings suggest that autoreactivity to the N-terminal portion of the PAGE protein family is associated with schizophrenia in a subset of patients with first-episode psychosis.

  • 1068.
    Zelenina, Marina
    et al.
    Nordic Centre of Excellence for Research in Water Imbalance Related Disorders (WIRED), Department of Woman and Child Health, Karolinska Institute.
    Li, Yanhong
    Glorieux, Isabelle
    Arnaud, Catherine
    Cristini, Christelle
    Decramer, Stéphane
    Aperia, Anita
    Casper, Charlotte
    Urinary aquaporin-2 excretion during early human development2006In: Pediatric nephrology (Berlin, West), ISSN 0931-041X, E-ISSN 1432-198X, Vol. 21, no 7, p. 947-952Article in journal (Refereed)
    Abstract [en]

    This study was undertaken to assess one of the determinants of kidney concentrating capacity, aquaporin-2 (AQP2), in order to understand the physiopathology of water balance in newborn babies. Urinary AQP2 excretion has been shown to be proportional to AQP2 level in the apical plasma membrane of the kidney collecting ducts and has been suggested as a marker of vasopressin (AVP) action. Urinary AQP2 excretion in the early postnatal period and at 3 weeks of age was measured in 123 neonates admitted during a 6-month period to the neonatal intensive care unit of the Children's Hospital of Toulouse, France. Clinical and biochemical data were collected for each child. During the first days after birth, higher urinary AQP2 was observed in boys than in girls (P=0.01) and positively correlated with urinary sodium/potassium (Na/K) ratio (r=0.33, P=0.01). When the babies had reached 3 weeks of age, urinary AQP2 was proportional to the gestational age at birth (r=0.33, P=0.0068) and daily weight gain (r=0.36, P=0.003). It did not correlate with urinary osmolality, which was overall very low in all babies. Urinary AQP2 was decreased in conditions of impaired renal function (r=-0.42, P=0.0005) and acidosis (P=0.03). Prenatal corticosteroid treatment had no significant impact on urinary AQP2 level. Our data show that urinary AQP2 correlates with the overall maturity of tubular function in human neonates. In babies at this early age, urinary AQP2 cannot serve as a direct marker of the renal action of AVP but reflects AQP2 expression level associated with different physiopathological conditions.

  • 1069. Zeleznik, Michael P.
    et al.
    Maguire Jr., Gerald Q.
    Baxter, Brent S.
    University of Utah.
    Noz, Marilyn E.
    New York University.
    Schimpf, James H.
    New York University.
    Horii, Steven C.
    New York University.
    PACS User Level Requirements1983In: Proceedings of the Society of Photo-Optical Instrumentation Engineers, ISSN 0361-0748, Vol. 418, p. 172-177Article in journal (Refereed)
  • 1070.
    Zetterberg, Lena
    et al.
    Uppsala University.
    Aquilonius, Sten-Magnus
    Uppsala University.
    Lindmark, Birgitta
    Uppsala University.
    Lundström, Erik
    Uppsala University.
    Stokes, Virgil
    Uppsala University.
    Färnstrand, Catarina
    Uppsala University.
    Halvorsen, Kjartan
    The Swedish School of Sport and Health Sciences.
    Objective assessment in cervical dystonia2004In: Proceedings from ESMAC 13th Annual Meeting of European Society of Movement Analysis of Adult and Children, 2004Conference paper (Refereed)
  • 1071.
    Zetterberg, Lena
    et al.
    Uppsala University.
    Halvorsen, Kjartan
    Swedish School of Sports and Health Sciences.
    Färnstrand, Catarina
    Uppsala University.
    Aquilonius, Sten-Magnus
    Uppsala University.
    Lindmark, Birgitta
    Uppsala University.
    Physiotherapy in cervical dystonia: six experimental single-case studies2008In: Physiotherapy Theory and Practice, ISSN 0959-3985, E-ISSN 1532-5040, Vol. 24, no 4, p. 275-290Article in journal (Refereed)
    Abstract [en]

    The aim of the study was to explore the outcome of a physiotherapy program targeted to improve the quality of life of people with cervical dystonia (CD) by reducing pain, improving awareness of postural orientation, increasing muscle strength, and reducing the effort of moving the head and neck. In six single case studies, the primary outcome measure for each case was the Cervical Dystonia Questionnaire (CDQ) to measure the impact of the program on the individuals' quality of life. Secondary outcome measures were identified for the different components of the physiotherapy program: Visual Analogue Scale (pain); Postural Orientation Index (postural orientation awareness); and Movement Energy Index (effort of moving head and neck). Each of the cases had the severity of their problems scored on the Toronto Western Spasmodic Torticollis Scale. The study period was 26 weeks: 2 weeks' baseline period, 4 weeks' treatment period, and 20 weeks' follow-up. All measures except the Movement Energy Index (MEI) and CDQ-24 were taken three times per week for the first 6 weeks of the study and then once at 3 and 6 months. The MEI was taken once a week during the pretreatment and the treatment periods and during the first 2 weeks of follow-up and also after 3 and 6 months of follow-up. The CDQ-24 was taken once in the pretreatment period, once after completion of treatment, once 2 weeks after treatment, and once at 3 and 6 months of follow-up. Five of the six case studies reported an increase in quality of life at 6-month follow-up, as measured on the CDQ-24. Three of the six cases reported a reduction in pain and severity of the dystonia and had improved scores on the postural orientation measure at 6-month follow-up. All six patients had a reduction in the movement energy scores, but this was not significant. The outcomes of the six case studies would suggest that further investigation is required to show the effectiveness of physiotherapy programs in the management of CD.

  • 1072.
    Zetterberg, Lena
    et al.
    Uppsala University.
    Halvorsen, Kjartan
    Swedish School of Sports and Health Sciences.
    Färnstrand, Catarina
    Uppsala University.
    Lundström, Erik
    Uppsala University.
    Lindmark, Birgitta
    Uppsala University.
    Aquilonius, Sten-Magnus
    Uppsala University.
    Objective assessment of cervical dystonia: a pilot study2005In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 112, no 4, p. 248-253Article in journal (Refereed)
    Abstract [en]

    Objectives - The aims were to characterize the movements in cervical dystonia (CD) by using an estimate of the mechanical power and work involved in the movements and to describe this through a movement energy index (MEI). Materials and methods - The subjects (patients n = 6, controls n = 6) were seated in front of a screen with a laser pointer attached to a headband while they performed standardized movements. A three-dimensional motion capture system was used and a test-retest was performed. Results - The mean value of MEI was significantly higher for the patients than for the controls. There was no significant difference between MEI from test to retest for the patients but there was a significant difference between MEI from test to retest for the controls. Conclusion - This study suggests that MEI could be a useful measure for the quantification of movement dysfunction in CD and thus an objective outcome measure in comparison of different therapies.

  • 1073. Zhang, B.
    et al.
    Tornmalm, Johan
    KTH, School of Engineering Sciences (SCI), Applied Physics, Experimental Biomolecular Physics.
    Widengren, Jerker
    KTH, School of Engineering Sciences (SCI), Applied Physics, Experimental Biomolecular Physics.
    Vakifahmetoglu-Norberg, H.
    Norberg, E.
    Characterization of the role of the Malate dehydrogenases to lung tumor cell survival2017In: Journal of Cancer, ISSN 1837-9664, E-ISSN 1837-9664, Vol. 8, no 11, article id 19373Article in journal (Refereed)
    Abstract [en]

    Cellular compartmentalization of biochemical processes in eukaryotic cells is critical for many functions including shuttling of reducing equivalents across membranes. Although coordination of metabolic flux between different organelles is vital for cell physiology, its impact on tumor cell survival is not well understood. By using an integrative approach, we have dissected the role of the key metabolic enzymes Malate dehydrogenases (MDH1 and MDH2) to the survival of Nonsmall Cell Lung Carcinomas. Here, we report that while both the MDH1 (cytosolic) and the MDH2 (mitochondrial) enzymes display elevated levels in patients compared to normal counterparts, only high expression of MDH1 is associated with poor prognosis. We further show that the MDH1 enzymatic activity is significantly higher in NSCLC cells than that of MDH2. Accordingly, genetic depletion of MDH1 leads to significantly higher toxicity than depletion of MDH2. These findings provide molecular insights into the metabolic characteristics of the malate isoenzymes and mark MDH1 as a potential therapeutic target in these tumors.

  • 1074.
    Zhang, Cheng
    et al.
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Aldrees, Mohammed
    Arif, Muhammad
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Li, Xiangyu
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Mardinoglu, Adil
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Aziz, Mohammad Azhar
    Elucidating the Reprograming of Colorectal Cancer Metabolism Using Genome-Scale Metabolic Modeling2019In: Frontiers in Oncology, ISSN 2234-943X, E-ISSN 2234-943X, Vol. 9, article id 681Article in journal (Refereed)
    Abstract [en]

    Colorectal cancer is the third most incidental cancer worldwide, and the response rate of current treatment for colorectal cancer is very low. Genome-scale metabolic models (GEMs) are systems biology platforms, and they had been used to assist researchers in understanding the metabolic alterations in different types of cancer. Here, we reconstructed a generic colorectal cancer GEM by merging 374 personalized GEMs from the Human Pathology Atlas and used it as a platform for systematic investigation of the difference between tumor and normal samples. The reconstructed model revealed the metabolic reprogramming in glutathione as well as the arginine and proline metabolism in response to tumor occurrence. In addition, six genes including ODC1, SMS, SRM, RRM2, SMOX, and SAT1 associated with arginine and proline metabolism were found to be key players in this metabolic alteration. We also investigated these genes in independent colorectal cancer patients and cell lines and found that many of these genes showed elevated level in colorectal cancer and exhibited adverse effect in patients. Therefore, these genes could be promising therapeutic targets for treatment of a specific colon cancer patient group.

  • 1075.
    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, Centres, 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 cancers2019In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 19, no 1, article id 684Article in journal (Refereed)
    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.

  • 1076.
    Zheng, Daoshan
    et al.
    Dept Canc Biol, 4500 San Pablo Rd, Jacksonville, FL 32224 USA..
    Williams, Cecilia
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Cellular and Clinical Proteomics. KTH, Centres, 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 cancers2018In: Cancer Letters, ISSN 0304-3835, E-ISSN 1872-7980, Vol. 438, p. 24-31Article, review/survey (Refereed)
    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.

  • 1077.
    Zheng, Yifan
    et al.
    KTH, School of Engineering Sciences (SCI), Physics.
    Yveborg, Moa
    Prismat Sensors AB, Roslagstullsbacken 21, S-10691 Stockholm, Sweden..
    Grönberg, Fredrik
    KTH, School of Engineering Sciences (SCI), Physics, Physics of Medical Imaging.
    Xu, Cheng
    KTH, School of Engineering Sciences (SCI), Physics, Physics of Medical Imaging.
    Su, Qianqian
    Tsinghua Univ, Minist Educ, Key Lab Particle & Radiat Imaging, Beijing 100084, Peoples R China.;Tsinghua Univ, Dept Engn Phys, Beijing 100084, Peoples R China..
    Danielsson, Mats
    KTH, School of Engineering Sciences (SCI), Physics, Physics of Medical Imaging.
    Persson, Mats
    KTH, School of Engineering Sciences (SCI), Physics, Physics of Medical Imaging.
    Robustness of optimal energy thresholds in photon-counting spectral CT2020In: Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment, ISSN 0168-9002, E-ISSN 1872-9576, Vol. 953, article id 163132Article in journal (Refereed)
    Abstract [en]

    An important question when developing photon-counting detectors for computed tomography is how to select energy thresholds. In this work thresholds are optimized by maximizing signal-difference-to-noise ratio squared (SDNR2) in an optimally weighted image and signal-to-noise ratio squared (SNR2) in a gadolinium basis image in a silicon-strip detector and a cadmium zinc telluride (CZT) detector, factoring in pileup and imperfect energy response based on real-world detector systems. To investigate to what extent one single set of thresholds could be applied in various imaging tasks, the robustness of optimal thresholds with 2 to 8 bins is examined with the variation of phantom thicknesses, target materials and detector configurations. In contrast to previous studies, the optimal threshold locations do not always increase with increasing attenuation if pileup is included. With respect to the tradeoff between higher SDNR2 or SNR2 and less data, setting optimal thresholds for a 30 cm phantom yields robust SDNR2 and setting optimal thresholds for a 50 cm phantom yields robust SNR2 with 6 to 8 bins in the silicon-strip detector. Furthermore, setting optimal thresholds for a 30 cm phantom yields robust SDNR2 or SNR2 with 6 to 8 bins and a pixel size less than or equal to 0.5 x 0.5 mm(2) in the CZT detector.

  • 1078. Zhu, Huilin
    et al.
    Fan, Yuebo
    Guo, Huan
    Huang, Dan
    He, Sailing
    KTH, School of Electrical Engineering (EES), Electromagnetic Engineering. KTH, School of Information and Communication Technology (ICT), Centres, Zhejiang-KTH Joint Research Center of Photonics, JORCEP.
    Reduced interhemispheric functional connectivity of children with autism spectrum disorder: evidence from functional near infrared spectroscopy studies2014In: Biomedical Optics Express, ISSN 2156-7085, E-ISSN 2156-7085, Vol. 5, no 4, p. 1262-1274Article in journal (Refereed)
    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.

  • 1079. 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, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Fang, C.
    Lu, H. -J
    Xu, T.
    Weiss, J.
    Duan, H.
    Uhlén, Mathias
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, 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 knowledgebase2013In: Circulation Research, ISSN 0009-7330, E-ISSN 1524-4571, Vol. 113, no 9, p. 1043-1053Article in journal (Refereed)
    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.

  • 1080.
    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 falling2010In: Gait & Posture, ISSN 0966-6362, E-ISSN 1879-2219, Vol. 31, no 4, p. 438-443Article in journal (Refereed)
    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.

  • 1081.
    Åkerborg, Örjan
    et al.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Spalinskas, Rapolas
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Pradhananga, Sailendra
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Anil, Anandashankar
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Höjer, Pontus
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Gene Technology. KTH, Centres, 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, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Gene Technology. KTH, Centres, 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 Pathways2019In: Circulation. Genomic and precision medicine, ISSN 2574-8300, Vol. 12, no 3, article id e002353Article in journal (Refereed)
    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.

  • 1082.
    Ånell, Rickard
    et al.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Environmental Physiology. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Centres, Swedish Aerospace Physiology Centre, SAPC.
    Grönkvist, Mikael
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Environmental Physiology. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Centres, Swedish Aerospace Physiology Centre, SAPC.
    Gennser, Mikael
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Environmental Physiology. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Centres, Swedish Aerospace Physiology Centre, SAPC.
    Eiken, Ola
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Environmental Physiology. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Centres, Swedish Aerospace Physiology Centre, SAPC.
    Letter to the Editor re: Evolution and Preservation of Venous Gas Emboli at Alternating High and Moderate Altitude Exposures In Response2020In: Aerospace Medicine and Human Performance, ISSN 2375-6314, E-ISSN 2375-6322, Vol. 91, no 5, p. 456-456Article in journal (Refereed)
  • 1083. 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 pigs2000In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 28, no 3, p. 818-823Article in journal (Refereed)
    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.

  • 1084. Åslund, M.
    et al.
    Cederström, Björn
    KTH, Superseded Departments, Physics.
    Lundqvist, M.
    Danielsson, Mats
    KTH, Superseded Departments, Physics.
    Scatter rejection in scanned multi-slit digital mammography2004In: Proceedings of SPIE - The International Society for Optical Engineering, 2004, no 1, p. 478-487Conference paper (Refereed)
    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.

  • 1085.
    Özcan, Orcun Orkan
    et al.
    Univ Strasbourg, Inst Neurosci Cellulaires & Integrat, CNRS, F-67000 Strasbourg, France..
    Wang, Xiaolu
    Erasmus MC, Dept Neurosci, NL-1105 BA Rotterdam, Netherlands..
    Binda, Francesca
    Univ Strasbourg, Inst Neurosci Cellulaires & Integrat, CNRS, F-67000 Strasbourg, France..
    Dorgans, Kevin
    Univ Strasbourg, Inst Neurosci Cellulaires & Integrat, CNRS, F-67000 Strasbourg, France..
    De Zeeuw, Chris I.
    Erasmus MC, Dept Neurosci, NL-1105 BA Rotterdam, Netherlands.;Netherlands Inst Neurosci, Amsterdam, Netherlands..
    Gao, Zhenyu
    Erasmus MC, Dept Neurosci, NL-1105 BA Rotterdam, Netherlands..
    Aertsen, Ad
    Univ Freiburg, Fac Biol, D-79104 Freiburg, Germany.;Univ Freiburg, Bernstein Ctr Freiburg, D-79104 Freiburg, Germany..
    Kumar, Arvind
    KTH, School of Electrical Engineering and Computer Science (EECS), Computer Science, Computational Science and Technology (CST).
    Isope, Philippe
    Univ Strasbourg, Inst Neurosci Cellulaires & Integrat, CNRS, F-67000 Strasbourg, France..
    Differential Coding Strategies in Glutamatergic and GABAergic Neurons in the Medial Cerebellar Nucleus2020In: Journal of Neuroscience, ISSN 0270-6474, E-ISSN 1529-2401, Vol. 40, no 1, p. 159-170Article in journal (Refereed)
    Abstract [en]

    The cerebellum drives motor coordination and sequencing of actions at the millisecond timescale through adaptive control of cerebellar nuclear output. Cerebellar nuclei integrate high-frequency information from both the cerebellar cortex and the two main excitatory inputs of the cerebellum: the mossy fibers and the climbing fiber collaterals. However, how nuclear cells process rate and timing of inputs carried by these inputs is still debated. Here, we investigate the influence of the cerebellar cortical output, the Purkinje cells, on identified cerebellar nuclei neurons in vivo in male mice. Using transgenic mice expressing Channelrhodopsin2 specifically in Purkinje cells and tetrode recordings in the medial nucleus, we identified two main groups of neurons based on the waveform of their action potentials. These two groups of neurons coincide with glutamatergic and GABAergic neurons identified by optotagging after Chrimson expression in VGLUT2-cre and GAD-cre mice, respectively. The glutamatergic-like neurons fire at high rate and respond to both rate and timing of Purkinje cell population inputs, whereas GABAergic-like neurons only respond to the mean population firing rate of Purkinje cells at high frequencies. Moreover, synchronous activation of Purkinje cells can entrain the glutamatergic-like, but not the GABAergic-like, cells over a wide range of frequencies. Our results suggest that the downstream effect of synchronous and rhythmic Purkinje cell discharges depends on the type of cerebellar nuclei neurons targeted.

19202122 1051 - 1085 of 1085
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