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  • 201. Baer, R
    et al.
    Eiken, Ola
    Karolinska Institutet.
    Balldin, U
    Effects of triglycyl-lysine-vasopressin on cardiovascular responses to orthostatic stress.1987Inngår i: Clinical Physiology, ISSN 0144-5979, E-ISSN 1365-2281, Vol. 7, nr 4, s. 329-35Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The influence of triglycyl-lysine-vasopressin (TGLVP) on cardiovascular responses to orthostatic stress was studied. Arterial pressures, heart rate (HR) and stroke volume (SV) were measured in eight healthy males subjected to 20 min 70 degrees head-up tilt. On different days they received either 0.01 mg/kg b.w. of TGLVP or a corresponding volume of 0.9% saline i.v. after 15 min supine rest. After the drug injection, in supine subjects, HR had decreased from 58 to 50 beats min-1, total peripheral resistance (TPR) was elevated by 29%, systolic (SAP) and diastolic pressure (DAP) had increased by 7 and 8 mmHg, respectively. During tilt, values for HR and SAP were similar with and without TGLVP whereas DAP and MAP were elevated 8 and 7 mmHg, respectively, by the drug. 4-8 min into the tilt, TGLVP caused an 8% sustained curtailment of SV. Both with and without the drug TPR increased by about 30% in response to head-up tilt. Thus, the marked peripheral arteriolar constriction after vasopressin in the supine position was not affected by head-up tilt. Tilting also abolished the drug-induced elevation in SAP, most likely explained by the reduction in SV. Although TPR was markedly increased by TGLVP during head-up tilt, reflected in the behaviour of DAP, the response of SV speaks against any beneficial effect of this drug on orthostatic tolerance in healthy subjects.

  • 202. Bagawath-Singh, Sunitha
    et al.
    Staaf, Elina
    Stoppelenburg, Arie Jan
    Spielmann, Thiemo
    KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik, Experimentell biomolekylär fysik.
    Kambayashi, Taku
    Widengren, Jerker
    KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik, Experimentell biomolekylär fysik.
    Johansson, Sofia
    Cytokines Induce Faster Membrane Diffusion of MHC Class I and the Ly49A Receptor in a Subpopulation of Natural Killer Cells2016Inngår i: Frontiers in Immunology, ISSN 1664-3224, E-ISSN 1664-3224, Vol. 7Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Cytokines have the potential to drastically augment immune cell activity. Apart from altering the expression of a multitude of proteins, cytokines also affect immune cell dynamics. However, how cytokines affect the molecular dynamics within the cell membrane of immune cells has not been addressed previously. Molecular movement is a vital component of all biological processes, and the rate of motion is, thus, an inherent determining factor for the pace of such processes. Natural killer (NK) cells are cytotoxic lymphocytes, which belong to the innate immune system. By fluorescence correlation spectroscopy, we investigated the influence of cytokine stimulation on the membrane density and molecular dynamics of the inhibitory receptor Ly49A and its ligand, the major histocompatibility complex class I allele H-2D(d), in freshly isolated murine NK cells. H-2D(d) was densely expressed and diffused slowly in resting NK cells. Ly49A was expressed at a lower density and diffused faster. The diffusion rate in resting cells was not altered by disrupting the actin cytoskeleton. A short-term stimulation with interleukin-2 or interferon- alpha + beta did not change the surface density of moving H-2D(d) or Ly49A, despite a slight upregulation at the cellular level of H-2D(d) by interferon-alpha + beta, and of Ly49A by IL-2. However, the molecular diffusion rates of both H-2D(d) and Ly49A increased significantly. A multivariate analysis revealed that the increased diffusion was especially marked in a subpopulation of NK cells, where the diffusion rate was increased around fourfold compared to resting NK cells. After IL-2 stimulation, this subpopulation of NK cells also displayed lower density of Ly49A and higher brightness per entity, indicating that Ly49A may homo-cluster to a larger extent in these cells. A faster diffusion of inhibitory receptors could enable a faster accumulation of these molecules at the immune synapse with a target cell, eventually leading to a more efficient NK cell response. It has previously been assumed that cytokines regulate immune cells primarily via alterations of protein expression levels or posttranslational modifications. These findings suggest that cytokines may also modulate immune cell efficiency by increasing the molecular dynamics early on in the response.

  • 203.
    Bahuguna, Jyotika
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsvetenskap och beräkningsteknik (CST).
    Structure-Dynamics relationship in basalganglia: Implications for brain function2016Doktoravhandling, monografi (Annet vitenskapelig)
    Abstract [en]

    In this thesis, I have used a combination of computational models such as mean field and spikingnetwork simulations to study various sub-circuits of basal ganglia. I first studied the striatum(chapter 2), which is the input nucleus of basal ganglia. The two types of Medium SpinyNeurons (MSNs), D1 and D2-MSNs, together constitute 98% of the neurons in striatum. Thecomputational models so far have treated striatum as a homogenous unit and D1 and D2 MSNs asinterchangeable subpopulations. This implied that a bias in a Go/No-Go decision is enforced viaexternal agents to the striatum (eg. cortico-striatal weights), thereby assigning it a passive role.New data shows that there is an inherent asymmetry in striatal circuits. In this work, I showedthat striatum due to its asymmetric connectivity acts as a decision transition threshold devicefor the incoming cortical input. This has significant implications on the function of striatum asan active participant in influencing the bias towards a Go/No-Go decision. The striatal decisiontransition threshold also gives mechanistic explanations for phenomena such as L-Dopa InducedDyskinesia (LID), DBS-induced impulsivity, etc. In chapter 3, I extend the mean field model toinclude all the nuclei of basal ganglia to specifically study the role of two new subpopulationsfound in GPe (Globus Pallidus Externa). Recent work shows that GPe, also earlier consideredto be a homogenous nucleus, has at least two subpopulations which are dichotomous in theiractivity with respect to the cortical Slow Wave (SWA) and beta activity. Since the data for thesesubpopulations are missing, a parameter search was performed for effective connectivities usingGenetic Algorithms (GA) to fit the available experimental data. One major result of this studyis that there are various parameter combinations that meet the criteria and hence the presenceof functional homologs of the basal ganglia network for both pathological (PD) and healthynetworks is a possibility. Classifying all these homologous networks into clusters using somehigh level features of PD shows a large variance, hinting at the variance observed among the PDpatients as well as their response to the therapeutic measures. In chapter 4, I collaborated on aproject to model the role of STN and GPe burstiness for pathological beta oscillations as seenduring PD. During PD, the burstiness in the firing patterns of GPe and STN neurons are shownto increase. We found that in the baseline state, without any bursty neurons in GPe and STN,the GPe-STN network can transition to an oscillatory state through modulating the firing ratesof STN and GPe neurons. Whereas when GPe neurons are systematically replaced by burstyneurons, we found that increase in GPe burstiness enforces oscillations. An optimal % of burstyneurons in STN destroys oscillations in the GPe-STN network. Hence burstiness in STN mayserve as a compensatory mechanism to destroy oscillations. We also propose that bursting inGPe-STN could serve as a mechanism to initiate and kill oscillations on short time scales, asseen in the healthy state. The GPe-STN network however loses the ability to kill oscillations inthe pathological state.

  • 204.
    Bahuguna, Jyotika
    et al.
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB. University of Freiburg, Germany.
    Aertsen, Ad
    University of Freiburg, Germany.
    Kumar, Arvind
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB. University of Freiburg, Germany.
    Existence and control of Go/No-Go decision transition threshold in the striatum2015Inngår i: PloS Computational Biology, ISSN 1553-734X, E-ISSN 1553-7358, Vol. 11, nr 4, artikkel-id e1004233Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A typical Go/No-Go decision is suggested to be implemented in the brain via the activation of the direct or indirect pathway in the basal ganglia. Medium spiny neurons (MSNs) in the striatum, receiving input from cortex and projecting to the direct and indirect pathways express D1 and D2 type dopamine receptors, respectively. Recently, it has become clear that the two types of MSNs markedly differ in their mutual and recurrent connectivities as well as feedforward inhibition from FSIs. Therefore, to understand striatal function in action selection, it is of key importance to identify the role of the distinct connectivities within and between the two types of MSNs on the balance of their activity. Here, we used both a reduced firing rate model and numerical simulations of a spiking network model of the striatum to analyze the dynamic balance of spiking activities in D1 and D2 MSNs. We show that the asymmetric connectivity of the two types of MSNs renders the striatum into a threshold device, indicating the state of cortical input rates and correlations by the relative activity rates of D1 and D2 MSNs. Next, we describe how this striatal threshold can be effectively modulated by the activity of fast spiking interneurons, by the dopamine level, and by the activity of the GPe via pallidostriatal backprojections. We show that multiple mechanisms exist in the basal ganglia for biasing striatal output in favour of either the `Go' or the `No-Go' pathway. This new understanding of striatal network dynamics provides novel insights into the putative role of the striatum in various behavioral deficits in patients with Parkinson's disease, including increased reaction times, L-Dopa-induced dyskinesia, and deep brain stimulation-induced impulsivity.

  • 205.
    Bai, Yunpeng
    et al.
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Weibull, Emilie
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Jönsson, Håkan
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Andersson Svahn, Helene
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Interfacing picoliter droplet microfluidics with addressable microliter compartments using fluorescence activated cell sorting2014Inngår i: Sensors and actuators. B, Chemical, ISSN 0925-4005, E-ISSN 1873-3077, Vol. 194, s. 249-254Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Droplet microfluidic platforms have, while enabling high-throughput manipulations and the assaying of single cell scale compartments, been lacking interfacing to allow macro scale access to the output from droplet microfluidic operations. Here, we present a simple and high-throughput method for individually directing cell containing droplets to an addressable and macro scale accessible microwell slide for downstream analysis. Picoliter aqueous droplets containing low gelling point agarose and eGFP expressing Escherichia coli (E. coli) are created in a microfluidic device, solidified to agarose beads and transferred into an aqueous buffer. A Fluorescence activated cell sorter (FACS) is used to sort agarose beads containing cells into microwells in which the growth and expansion of cell colonies is monitored. We demonstrate fast sorting and high accuracy positioning of sorted 15 μm gelled droplet agarose beads into microwells (14 × 48) on a 25 mm × 75 mm microscope slide format using a FACS with a 100 μm nozzle and an xy-stage. The interfacing method presented here enables the products of high-throughput or single cell scale droplet microfluidics assays to be output to a wide range of microtiter plate formats familiar to biological researchers lowering the barriers for utilization of these microfluidic platforms.

  • 206. Bak, Z
    et al.
    Abildgård, L
    Lisander, B
    Janerot-Sjöberg, B
    Hälsouniversitetet, Linköping University.
    Transesophageal echocardiographic hemodynamic monitoring during preoperative acute normovolemic hemodilution.2000Inngår i: Anesthesiology, ISSN 0003-3022, E-ISSN 1528-1175, Vol. 92, nr 5, s. 1250-6Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Preoperative acute normovolemic hemodilution may compromise oxygen transport. The aims of our study were to describe the hemodynamic effects of normovolemic hemodilution and to determine its effect on systolic and diastolic cardiac function by multiplane transesophageal echocardiography.

    METHODS: In eight anesthetized patients (aged 13-51 yr) without heart disease, hemoglobin was reduced in steps from 123 +/- 8 (mean +/- SD) to 98 +/- 3 and to 79 +/- 5 g/l. Hemodynamic measurements (intravascular pressures, thermodilution cardiac output, and echocardiographic recordings) were obtained during a stabilization period and at each level of hemodilution. Left ventricular wall motion was monitored continuously, and Doppler variables, annular motion, and changes in ejection fractional area were analyzed off-line.

    RESULTS: During hemodilution, cardiac output by thermodilution increased by 16 +/- 7% and 26 +/- 10%, corresponding well to the increase in cardiac output as measured by Doppler (difference, 0.32 +/- 1.2 l/min). Systemic vascular resistance fell 16 +/- 14% and 23 +/- 9% and pulmonary capillary wedge pressure increased slightly (2 +/- 2 mmHg), whereas other pressures, heart rate, wall motion, and diastolic Doppler variables remained unchanged. Ejection fractional area change increased from 44 +/- 7% to 54 +/- 10% and 60 +/- 9% as a result of reduced end-systolic and increased end-diastolic left ventricular areas.

    CONCLUSIONS: A reduction in hemoglobin to 80 g/l during acute normovolemic hemodilution does not normally compromise systolic or diastolic myocardial function as determined by transesophageal echocardiography. Preload, left ventricular ejection fraction, and cardiac output increase with a concomitant fall in systemic vascular resistance.

  • 207. Bak, Z
    et al.
    Sjöberg, F
    Eriksson, O
    Steinvall, I
    Janerot-Sjöberg, Birgitta
    Department of Clinical Physiology, Heart Centre, Linköping University Hospital, Sweden.
    Cardiac dysfunction after burns2008Inngår i: Burns, ISSN 0305-4179, E-ISSN 1879-1409, Vol. 34, nr 5, s. 603-609Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVES: Using transoesophageal echocardiography (TEE) we investigated the occurrence, and the association of possible abnormalities of motion of the regional wall of the heart (WMA) or diastolic dysfunction with raised troponin concentrations, or both during fluid resuscitation in patients with severe burns.

    PATIENTS AND METHODS: Ten consecutive adults (aged 36-89 years, two women) with burns exceeding 20% total burned body surface area who needed mechanical ventilation were studied. Their mean Baux index was 92.7, and they were resuscitated according to the Parkland formula. Thirty series of TEE examinations and simultaneous laboratory tests for myocyte damage were done 12, 24, and 36h after the burn.

    RESULTS: Half (n=5) the patients had varying grades of leakage of the marker that correlated with changeable WMA at 12, 24 and 36h after the burn (p< or =0.001, 0.044 and 0.02, respectively). No patient had WMA and normal concentrations of biomarkers or vice versa. The mitral deceleration time was short, but left ventricular filling velocity increased together with stroke volume.

    CONCLUSION: Acute myocardial damage recorded by both echocardiography and leakage of troponin was common, and there was a close correlation between them. This is true also when global systolic function is not deteriorated. The mitral flow Doppler pattern suggested restrictive left ventricular diastolic function.

  • 208. Bak, Z
    et al.
    Sjöberg, F
    Rousseau, A
    Steinvall, I
    Janerot-Sjöberg, Birgitta
    Department of Clinical Physiology, Heart Center, Linköping University Hospital.
    Human cardiovascular dose-response to supplemental oxygen2007Inngår i: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 191, nr 1, s. 15-24Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    AIM: The aim of the study was to examine the central and peripheral cardiovascular adaptation and its coupling during increasing levels of hyperoxaemia. We hypothesized a dose-related effect of hyperoxaemia on left ventricular performance and the vascular properties of the arterial tree.

    METHODS: Oscillometrically calibrated arterial subclavian pulse trace data were combined with echocardiographic recordings to obtain non-invasive estimates of left ventricular volumes, aortic root pressure and flow data. For complementary vascular parameters and control purposes whole-body impedance cardiography was applied. In nine (seven males) supine, resting healthy volunteers, aged 23-48 years, data was collected after 15 min of air breathing and at increasing transcutaneous oxygen tensions (20, 40 and 60 kPa), accomplished by a two group, random order and blinded hyperoxemic protocol.

    RESULTS: Left ventricular stroke volume [86 +/- 13 to 75 +/- 9 mL (mean +/- SD)] and end-diastolic area (19.3 +/- 4.4 to 16.8 +/- 4.3 cm(2)) declined (P < 0.05), and showed a linear, negative dose-response relationship to increasing arterial oxygen levels in a regression model. Peripheral resistance and characteristic impedance increased in a similar manner. Heart rate, left ventricular fractional area change, end-systolic area, mean arterial pressure, arterial compliance or carbon dioxide levels did not change.

    CONCLUSION: There is a linear dose-response relationship between arterial oxygen and cardiovascular parameters when the systemic oxygen tension increases above normal. A direct effect of supplemental oxygen on the vessels may therefore not be excluded. Proximal aortic and peripheral resistance increases from hyperoxaemia, but a decrease of venous return implies extra cardiac blood-pooling and compensatory relaxation of the capacitance vessels.

  • 209. Bak, Zoltan
    et al.
    Sjöberg, Folke
    Hälsouniversitetet, Linköping University.
    Eriksson, Olle
    Steinvall, Ingrid
    Janerot-Sjoberg, Birgitta
    KTH, Skolan för teknik och hälsa (STH), Medicinsk teknik.
    Hemodynamic changes during resuscitation after burns using the Parkland formula2009Inngår i: Journal of Trauma, ISSN 0022-5282, E-ISSN 1529-8809, Vol. 66, nr 2, s. 329-336Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: The Parkland formula (2-4 mL/kg/burned area of total body surface area %) with urine output and mean arterial pressure (MAP) as endpoints for the fluid resuscitation in burns is recommended all over the world. There has recently been a discussion on whether central circulatory endpoints should be used instead, and also whether volumes of fluid should be larger. Despite this, there are few central hemodynamic data available in the literature about the results when the formula is used correctly.

    METHODS: Ten burned patients, admitted to our unit early, and with a burned area of >20% of total body surface area were investigated at 12, 24, and 36 hours after injury. Using transesophageal echocardiography, pulmonary artery catheterization, and transpulmonary thermodilution to monitor them, we evaluated the cardiovascular coupling when urinary output and MAP were used as endpoints.

    RESULTS: Oxygen transport variables, heart rate, MAP, and left ventricular fractional area, did not change significantly during fluid resuscitation. Left ventricular end-systolic and end-diastolic area and global end-diastolic volume index increased from subnormal values at 12 hours to normal ranges at 24 hours after the burn. Extravascular lung water: intrathoracal blood volume ratio was increased 12 hours after the burn.

    CONCLUSIONS: Preload variables, global systolic function, and oxygen transport recorded simultaneously by three separate methods showed no need to increase the total fluid volume within 36 hours of a major burn. Early (12 hours) signs of central circulatory hypovolemia, however, support more rapid infusion of fluid at the beginning of treatment.

  • 210. Bali, TC
    et al.
    Kounalakis, SN
    Eiken, Ola
    KTH, Skolan för teknik och hälsa (STH), Naturvetenskap och biomedicin, Omgivningsfysiologi. KTH, Skolan för teknik och hälsa (STH), Centra, Centrum för flyg- och rymdfysiologi, SAPC.
    Mekjavic, IB
    PlanHab: The effects of 21-day hypoxic confinement and unloading/inactivity on regional body composition and muscle strength2015Konferansepaper (Fagfellevurdert)
  • 211.
    Bamzar, Roya
    et al.
    KTH, Skolan för arkitektur och samhällsbyggnad (ABE), Centra, Centrum för bank och finans, Cefin.
    Ceccato, Vania
    KTH, Skolan för arkitektur och samhällsbyggnad (ABE), Centra, Centrum för bank och finans, Cefin.
    The nature and the geography of elderly injuries in Sweden2015Inngår i: GeoJournal, ISSN 0343-2521, E-ISSN 1572-9893, Vol. 80, nr 2, s. 279-299Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    This study assesses the nature and the geography of elderly injuries in Sweden. The most dominant types of accidents affecting the elderly in their homes and near environments are identified by using county-specific data from 2001 to 2010 followed by a correlation analysis of possible environmental factors underlying patterns of falls among the elderly. Geographical information systems are used to map rates by type. Slipping, tripping and stumbling are the causes of more than half of cases of elderly falls in Sweden, and is more typical in the Northern counties. Findings also show there has been a rise in rates of elderly falls since 2001 in most of the Southern counties, especially in Östergötland and Skåne Counties. Population age and gender affect the ecology of geography of fall rates and counties experiencing long cold winters tend to show higher rates of indoor falls than those with warmer temperature across the year. The article finalizes with a discussion of the results and implication for future research.

  • 212.
    Bamzar, Roya
    et al.
    KTH, Skolan för arkitektur och samhällsbyggnad (ABE), Samhällsplanering och miljö, Urbana och regionala studier.
    Ceccato, Vania
    KTH, Skolan för arkitektur och samhällsbyggnad (ABE), Samhällsplanering och miljö, Urbana och regionala studier.
    The regional ecology of elderly falls in Sweden2016Inngår i: GeoJournal, ISSN 0343-2521, E-ISSN 1572-9893, Vol. 81, nr 1, s. 23-36Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The study assesses exploratory the geography of the elderly fall in Sweden in relation to the ecology of the socio-demographic characteristics of the Swedes older population. Kendall Test is used to measure the association between elderly fall rates and demographic, socio-economic characteristics of the population, costs of elderly care and accessibility measures at county level. Results show a number of significant associations: high rates of the elderly fall are associated with high cost of the elderly care but also low rate of elderly fall and good accessibility to basic services (e.g., grocery store, health care and cash machines). The articles finalizes with reflections of the results and suggestions for future research.

  • 213.
    Ban, Yifang
    et al.
    KTH, Skolan för arkitektur och samhällsbyggnad (ABE), Samhällsplanering och miljö, Geodesi och geoinformatik.
    Fredman, David
    Jonsson, Martin
    Svensson, Leif
    Multi-Criteria Evaluations for Improved Placement of Defibrillators: Preliminary Results2013Inngår i: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 128, nr 22, s. 78-Artikkel i tidsskrift (Annet vitenskapelig)
  • 214.
    Banerjee, Indradumna
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Nanobioteknologi.
    Point of care microfluidic tool development for resource limited settings2019Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    The development of point of care diagnostics using recent advances in microfluidics have the potential to transform health care in several ways, especially in resource limited settings with limited access to advanced health care infrastructure. However, translating a point of care device to reality is often a challenging task because of the complexities involved in integrating a number of diverse engineering concepts into an easy to use, accurate and portable device. This thesis focuses on miniaturization of crucial diagnostic laboratory tools, that can be used in a portable point of care format without compromising on the accuracy or performance. The first part of the thesis (Paper I-III) focuses on understanding and applying elasto-inertial microfluidics, which is a label-free and passive bio-particle sorting and separation method. A basic understanding of particle trajectories in both inertial (Paper I) and visco-elastic flows (Paper II) is established, followed by an investigation on the combined effects of inertia and elasticity (Paper III). The second part of the thesis (Paper IV-VI) focuses on developing integrated microfluidic platforms, each of which addresses different aspects of point of care diagnostic applications. The applications include neonatal diagnostics using a hand-driven Slipdisc technique (Paper IV), rapid nucleic acid quantification using a novel precipitate-based detection on a centrifugal microfluidics platform (Paper V), and hematocrit level measurement in blood using a portable lab-on- Disc platform operated by a mobile phone (Paper VI). The proof of concept microfluidic tools presented in the scope of this thesis have the potential to replace a number of functions of standard laboratory equipment, at a fraction of the price and without compromising performance. Hence, the different methods developed should contribute towards decentralization of medical testing laboratories, making healthcare accessible to one and all.

  • 215.
    Banerjee, Indradumna
    et al.
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Nanobioteknologi.
    Ganeshappa Aralaguppe, Shambhu Prasad
    Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institute, Sweden..
    Lapins, Noa
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Nanobioteknologi.
    Zhang, Wang
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab. Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institute, Sweden..
    Kazemzadeh, Amin
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Nanobioteknologi.
    Sönnerborg, Anders
    Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institute, Sweden..
    Neogi, Ujjwal
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Nanobioteknologi. Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institute, Sweden..
    Russom, Aman
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Microfluidic Centrifugation Assisted Precipitation based DNA QuantificationManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    Nucleic acid amplification methods are increasingly being used to detect trace quantities of DNA in samples for various diagnostic applications. However, quantifying the amount of DNA from such methods often require time consuming purification, washing or labeling step. Here, we report a novel microfluidic centrifugation assisted precipitation (uCAP) method for single-step DNA quantification. The method is based on formation of a visible precipitate, that can be quantified, when an intercalating dye (GelRed) is added to DNA sample and centrifuged for few seconds. We describe the mechanism leading to the precipitation phenomenon. We utilize centrifugal microfluidics to precisely control the formation of visible and quantifiable mass. Using a standard CMOS sensor for imaging, we report a detection limit of 45 ng/ul. Furthermore, using an integrated Lab-on-DVD platform we recently developed, the detection limit was lowered to 10 ng/ul, which is comparable to current commercially available instruments for DNA quantification. As a proof of principle, we demonstrate the quantification of LAMP products for a HIV-1B type genome containing plasmid on the Lab-on-DVD platform. The simple DNA quantification system could facilitate advanced molecular diagnosis at point of care.

  • 216. Bannow, J.
    et al.
    Benjamins, J. -W
    Wohlert, Jakob
    KTH, Skolan för kemivetenskap (CHE), Fiber- och polymerteknologi. KTH, Skolan för kemivetenskap (CHE), Centra, Wallenberg Wood Science Center.
    Löbmann, K.
    Svagan, Anna J.
    KTH, Skolan för kemivetenskap (CHE), Fiber- och polymerteknologi. KTH, Skolan för kemivetenskap (CHE), Centra, Wallenberg Wood Science Center.
    Solid nanofoams based on cellulose nanofibers and indomethacin—the effect of processing parameters and drug content on material structure2017Inngår i: International Journal of Pharmaceutics, ISSN 0378-5173, E-ISSN 1873-3476, Vol. 526, nr 1-2, s. 291-299Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The unique colloidal properties of cellulose nanofibers (CNF), makes CNF a very interesting new excipient in pharmaceutical formulations, as CNF in combination with some poorly-soluble drugs can create nanofoams with closed cells. Previous nanofoams, created with the model drug indomethacin, demonstrated a prolonged release compared to films, owing to the tortuous diffusion path that the drug needs to take around the intact air-bubbles. However, the nanofoam was only obtained at a relatively low drug content of 21 wt% using fixed processing parameters. Herein, the effect of indomethacin content and processing parameters on the foaming properties was analysed. Results demonstrate that a certain amount of dissolved drug is needed to stabilize air-bubbles. At the same time, larger fractions of dissolved drug promote coarsening/collapse of the wet foam. The pendant drop/bubble profile tensiometry was used to verify the wet-foam stability at different pHs. The pH influenced the amount of solubilized drug and the processing-window was very narrow at high drug loadings. The results were compared to real foaming-experiments and solid state analysis of the final cellular solids. The parameters were assembled into a processing chart, highlighting the importance of the right combination of processing parameters (pH and time-point of pH adjustment) in order to successfully prepare cellular solid materials with up to 46 wt% drug loading.

  • 217. Bao, D.
    et al.
    Zou, Zhuo
    KTH, Skolan för informations- och kommunikationsteknik (ICT), Industriell och Medicinsk Elektronik. KTH, Skolan för informations- och kommunikationsteknik (ICT), Centra, VinnExcellence Center for Intelligence in Paper and Packaging, iPACK.
    Huan, Y.
    Zhai, Chuanying
    KTH, Skolan för informations- och kommunikationsteknik (ICT), Industriell och Medicinsk Elektronik. KTH, Skolan för informations- och kommunikationsteknik (ICT), Centra, VinnExcellence Center for Intelligence in Paper and Packaging, iPACK.
    Bagaian, T.
    Tenhunen, Hannu
    KTH, Skolan för informations- och kommunikationsteknik (ICT), Industriell och Medicinsk Elektronik. KTH, Skolan för informations- och kommunikationsteknik (ICT), Centra, VinnExcellence Center for Intelligence in Paper and Packaging, iPACK.
    Källbäck, B.
    Zheng, Lirong
    KTH, Skolan för informations- och kommunikationsteknik (ICT), Industriell och Medicinsk Elektronik. KTH, Skolan för informations- och kommunikationsteknik (ICT), Centra, VinnExcellence Center for Intelligence in Paper and Packaging, iPACK. State Key Laboratory of ASIC and System, Fudan University, Shanghai, China .
    A smart catheter system for minimally invasive brain monitoring2015Inngår i: Proceedings of the International Conference on Biomedical Electronics and Devices, SciTePress, 2015, s. 198-203Konferansepaper (Fagfellevurdert)
    Abstract [en]

    This paper demonstrates a smart catheter system with intracranial pressure (ICP) and temperature sensing capability which is designed for real-time monitoring in traumatic brain injury (TBI) therapy. It uses a single flexible catheter with a 1 mm (3 Fr) diameter that integrates electrodes and sophisticated silicon chip on flexible substrates, enabling multimodality monitoring of physiological signals. A micro-electromechanical-system (MEMS) catheter pressure sensor is mounted on the distal end. It can be used for detecting both pressure and temperature by different switch configurations, which minimizes the size of catheter and reduces the cost. The interconnects (signalling conductors) are printed on a bio-compatible flexible substrate, and the sensor is interfaced with an embedded electronic system at the far-end. The electronic system consists of analog front end with analog-to-digital converter (ADC), a microcontroller, and data interface to the hospital infrastructure with a graphical user interface (GUI). The overall smart catheter system achieves a pressure sensing root mean square error (RMSE) of ±1.5 mmHg measured from 20 mmHg to 300 mmHg above 1 atm and a temperature sensing RMSE of ±0.08°C measured from 32°C to 42°C. The sampling rate can be up to 10S/s. The in vivo performance is demonstrated in laboratory animals.

  • 218. Baptista La, Filipa Martins
    et al.
    Sundberg, Johan
    KTH, Skolan för datavetenskap och kommunikation (CSC), Tal, musik och hörsel, TMH, Musikakustik.
    Pregnancy and the Singing Voice: Reports From a Case Study2012Inngår i: Journal of Voice, ISSN 0892-1997, E-ISSN 1873-4588, Vol. 26, nr 4, s. 431-439Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objectives. Significant changes in body tissues occur during pregnancy; however, literature concerning the effects of pregnancy on the voice is sparse, especially concerning the professional classically trained voice. Hypotheses. Hormonal variations and associated bodily changes during pregnancy affect phonatory conditions, such as vocal fold motility and glottal adduction. Design. Longitudinal case study with a semiprofessional classically trained singer. Methods. Audio, electrolaryngograph, oral pressure, and air flow signals were recorded once a week during the last 12 weeks of pregnancy, 48 hours after birth and during the following consecutive 11 weeks. Vocal tasks included diminuendo sequences of the syllable /pae/sung at various pitches, and performing a Lied. Phonation threshold pressures (PTPs) and collision threshold pressures (CTPs), normalized amplitude quotient (NAQ), alpha ratio, and the dominance of the voice source fundamental were determined. Concentrations of sex female steroid hormones were measured on three occasions. A listening test of timbral brightness and vocal fatigue was carried out. Results. Results demonstrated significantly elevated concentrations of estrogen and progesterone during pregnancy, which were considerably reduced after birth. During pregnancy, CTPs and PTPs were high; and NAQ, alpha ratio, and dominance of the voice source fundamental suggested elevated glottal adduction. In addition, a perceptible decrease of vocal brightness was noted. Conclusions. The elevated CTPs and PTPs during pregnancy suggest reduced vocal fold motility and increased glottal adduction. These changes are compatible with expected effects of elevated concentrations of estrogen and progesterone on tissue viscosity and water retention.

  • 219. Barman, Linda
    Striving for Autonomy: Health sciences teachers’ enactment of policy2015Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Abstract This thesis explores how teachers within the health sciences enact education policy. The questions address how teachers’ choices related to the design of courses and curricula are made in the light of reforms that emphasise standardisation and transparency. Employing a hermeneutical framework teachers’ enactment were regarded as a meaning-making process shown through reason and action. In line with the interpretative approach, the two research projects were performed with qualitative methods. The first research project (study I and II) concerned how teachers’ understood and carried out changes in course design related to the implementation of outcome-based education and the European Bologna Process. For that purpose, course material and interview data was analysed. The second research project (study III and IV), was conducted to deepen the understanding of findings from the first project. A group of teachers who conducted major changes related to previous reform was chosen and studied with a narrative approach when they engaged in the development of teaching and learning. In particular, the teachers’ development of assessment criteria of students’ clinical competencies was studied over one year. A body of literature report on how teachers conceptualise teaching and learning. Based on those studies there has been an emphasis on supporting teachers’ shift in views regarding teaching and learning. Related to recent reforms in higher education, it is however suggested that teachers are less free to decide upon educational matters, and hence individual teachers’ deepened understanding are not enough for development of practice to occur. The findings in this thesis suggest that wide interpretations of education policy in combination with pedagogical knowledge may benefit educational development in practice. Teachers were found to approach outcome-based education when introduced as policy in four different ways, with outcome blind, technocratic, pragmatic or ideological approach. These approaches were related to student-centred learning to more or less extent, and to greater or lesser autonomy in the decision-making related to course design. The studies showed how teachers’ experience a tension between bureaucratic demands and what is emphasised through teaching and learning theory. For some teachers this meant that theoretical constructs were applied in instrumental ways and that pedagogy equated the bureaucratic and rational standards involved in quality control. The findings suggest however, that learning and development can be promoted through education policy but that teachers’ local practices should be supported.

  • 220.
    Barnkob, Rune
    et al.
    Tech Univ Denmark, Lyngby, Denmark .
    Iranmanesh, Ida
    KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik, Biomedicinsk fysik och röntgenfysik.
    Wiklund, Martin
    KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik, Biomedicinsk fysik och röntgenfysik.
    Bruus, Henrik
    Tech Univ Denmark, Lyngby, Denmark .
    Measuring acoustic energy density in microchannel acoustophoresis using a simple and rapid light-intensity method2012Inngår i: Lab on a Chip, ISSN 1473-0197, E-ISSN 1473-0189, Vol. 12, nr 13, s. 2337-2344Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We present a simple and rapid method for measuring the acoustic energy density in microchannel acoustophoresis based on light-intensity measurements of a suspension of particles. The method relies on the assumption that each particle in the suspension undergoes single-particle acoustophoresis. It is validated by the single-particle tracking method, and we show by proper re-scaling that the re-scaled light intensity plotted versus re-scaled time falls on a universal curve. The method allows for analysis of moderate-resolution images in the concentration range encountered in typical experiments, and it is an attractive alternative to particle tracking and particle image velocimetry for quantifying acoustophoretic performance in microchannels.

  • 221. Bartonek, A.
    et al.
    Lidbeck, C. M.
    Gutierrez-Farewik, Elena
    KTH, Skolan för teknikvetenskap (SCI), Mekanik, Biomekanik.
    Influence of external visual focus on gait in children with bilateral cerebral palsy2016Inngår i: Pediatric Physical Therapy, ISSN 0898-5669, E-ISSN 1538-005X, Vol. 28, nr 4, s. 393-399Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose: To explore whether focusing a target influenced gait in children with cerebral palsy (CP) and typical development (TD). Methods: Thirty children with bilateral CP (Gross Motor Function Classification System [GMFCS] I-III) and 22 with TD looked at a light at walkway end (Gaze Target) while walking and returned (No Target). Results: During Gaze versus No Target, children with TD reduced temporal-spatial parameters and movements in the sagittal (SPM) and transverse planes. In comparison, during Gaze Target, children in CP1 (GMFCS I) had larger trunk SPM, children in CP2 (GMFCS II) larger neck (SPM), and children in CP3 (GMFCS III) greater head and neck frontal plane movements, and reduced cadence and single support. Conclusions: Focusing a target altered gait in children with CP. Children in CP1 reduced movements similar to children with TD, children in CP2 behaved nearly unchanged, whereas children in CP3 reduced movements and temporalspatial parameters, potentially as a consequence of lack of sensory information from lower limbs.

  • 222.
    Bartonek, Asa
    et al.
    Karolinska Inst, Womens & Childrens Hlth, Motoriklab, Stockholm, Sweden..
    Lidbeck, Cecilia
    Karolinska Inst, Womens & Childrens Hlth, Stockholm, Sweden..
    Hellgren, Kerstin
    Karolinska Inst, Clin Neurosci, Stockholm, Sweden..
    Gutierrez-Farewik, Elena
    KTH, Skolan för teknikvetenskap (SCI), Mekanik. KTH, Skolan för teknikvetenskap (SCI), Centra, BioMEx. Karolinska Inst, Womens & Childrens Hlth, Stockholm, Sweden..
    Head and Trunk Movements During Turning Gait in Children with Cerebral Palsy2019Inngår i: Journal of motor behavior, ISSN 0022-2895, E-ISSN 1940-1027, Vol. 51, nr 4, s. 362-370Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Thirty children with cerebral palsy (CP) and 22 typical developing (TD) were tested with 3D-gait analysis. At turning, trunk rotation was larger in CP2 (GMFCS II) than in TD and CP1 (GMFCS I), and head flexion was larger in CP3 (GMFCS III) than TD. Maximum head and trunk flexion values during the entire trial were larger in CP3 than in the other groups, and trunk flexion was larger in CP2 than in TD. Trial time increased with GMFCS-level. Less trunk rotation than TD and CP1 reflects spatial insecurity in CP2, which in CP3 is compensated by the walker. The flexed head and trunk in CP3 and trunk in CP2 may reflect deficits in proprioception and sensation requiring visual control of the lower limbs.

  • 223. Bartonek, Asa
    et al.
    Lidbeck, Cecilia M.
    Pettersson, Robert
    KTH, Skolan för teknikvetenskap (SCI), Mekanik, Strukturmekanik.
    Weidenhielm, Eva Brostrom
    Eriksson, Marie
    Gutierrez-Farewik, Elena
    KTH, Skolan för teknikvetenskap (SCI), Mekanik, Strukturmekanik.
    Influence of heel lifts during standing in children with motor disorders2011Inngår i: Gait & Posture, ISSN 0966-6362, E-ISSN 1879-2219, Vol. 34, nr 3, s. 426-431Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Heel wedges may influence standing posture but how and to what extent are unknown. Thirty-two children with motor disorders - 16 with arthrogryposis multiplex congenita (AMC) and 16 with cerebral palsy (CP) - and 19 control children underwent a three-dimensional motion analysis. Unassisted standing during 20s with shoes only and with heel lifts of 10,20 and 30 mm heights was recorded in a randomized order. The more weight-bearing limb or the right limb was chosen for analysis. In both the AMC and CP groups, significant changes were seen between various heel lifts in ankle, knee and pelvis, and in the control group in the ankle only. Between orthosis and non-orthosis users significant differences were seen between different heel lift conditions in ankle, knee and trunk in the AMC group and in the ankle in the CP group. Pelvis position changed toward less anterior tilt with increasing heel height, but led to increasing knee flexion in most of the children, except for the AMC Non-Ort group. Children with AMC and CP represent different motor disorders, but the heel wedges had a similar influence on pelvis, hip and knee positions in all children with CP and in the AMC orthosis users. A challenge is to apply heel heights adequate to each individual's orthopaedic and neurologic conditions to improve biomechanical alignment with respect to all body segments.

  • 224. Basile, Walter
    et al.
    Sachenkova, Oxana
    Light, Sara
    Elofsson, Arne
    KTH, Centra, SeRC - Swedish e-Science Research Centre.
    High GC content causes orphan proteins to be intrinsically disordered2017Inngår i: PloS Computational Biology, ISSN 1553-734X, E-ISSN 1553-7358, Vol. 13, nr 3, artikkel-id e1005375Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    De novo creation of protein coding genes involves the formation of short ORFs from noncoding regions; some of these ORFs might then become fixed in the population These orphan proteins need to, at the bare minimum, not cause serious harm to the organism, meaning that they should for instance not aggregate. Therefore, although the creation of short ORFs could be truly random, the fixation should be subjected to some selective pressure. The selective forces acting on orphan proteins have been elusive, and contradictory results have been reported. In Drosophila young proteins are more disordered than ancient ones, while the opposite trend is present in yeast. To the best of our knowledge no valid explanation for this difference has been proposed. To solve this riddle we studied structural properties and age of proteins in 187 eukaryotic organisms. We find that, with the exception of length, there are only small differences in the properties between proteins of different ages. However, when we take the GC content into account we noted that it could explain the opposite trends observed for orphans in yeast (low GC) and Drosophila (high GC). GC content is correlated with codons coding for disorder promoting amino acids. This leads us to propose that intrinsic disorder is not a strong determining factor for fixation of orphan proteins. Instead these proteins largely resemble random proteins given a particular GC level. During evolution the properties of a protein change faster than the GC level causing the relationship between disorder and GC to gradually weaken.

  • 225. Baskaran, Karthikeyan
    et al.
    Rosén, Robert
    KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik, Biomedicinsk fysik och röntgenfysik.
    Lewis, Peter
    Unsbo, Peter
    Gustafsson, Jörgen
    Benefit of Adaptive Optics Aberration Correction at Preferred Retinal Locus2012Inngår i: Optometry and Vision Science, ISSN 1040-5488, E-ISSN 1538-9235, Vol. 89, nr 9Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose: To investigate the effect of eccentric refractive correction and full aberration correction on both high and low contrast grating resolution at the preferred retinal locus (PRL) of a single low vision subject with a longstanding central scotoma.

    Methods: The subject was a 68 year-old female with bilateral absolute central scotoma due to Stargardt’s disease. She has developed a single PRL located 25° nasally of the damaged macula in her left eye, this being the better of the two eyes. High- (100%) and low contrast (25% & 10%) grating resolution acuity was evaluated using four different correction conditions. The first two corrections were solely refractive error corrections; namely habitual spectacle correction and full sphero-cylindrical correction. The latter two corrections were two versions of adaptive optics corrections of all aberrations; namely full sphero-cylindrical refractive correction with additional aberration correction and habitual spectacle correction with aberration correction.

    Results: The mean high contrast (100%) resolution acuity with her habitual correction was 1.06 logMAR, which improved to 1.00 logMAR with full sphero-cylindrical correction. Under the same conditions, low contrast (25%) acuity improved from 1.30 logMAR to 1.14 logMAR. With adaptive optics aberration correction, the high contrast resolution acuities improved to 0.92/0.89 logMAR and the low contrast acuities, to 1.06/1.04 logMAR under both correction modalities. The low contrast (10%) resolution acuity was 1.34 logMAR with adaptive optics aberration correction; however, with purely refractive error corrections she was unable to identify the orientation of the gratings.

    Conclusion: Correction of all aberrations using adaptive optics improves both high and low contrast resolution acuity at the PRL of a single low vision subject with longstanding absolute central scotoma.

  • 226. Baskaran, Karthikeyan
    et al.
    Unsbo, Peter
    KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik, Biomedicinsk fysik och röntgenfysik.
    Gustafsson, Jörgen
    Influence of Age on Peripheral Ocular Aberrations2011Inngår i: Optometry and Vision Science, ISSN 1040-5488, E-ISSN 1538-9235, Vol. 88, nr 9, s. 1088-1098Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose. To compare peripheral lower and higher order aberrations across the horizontal (+/- 40 degrees) and inferior (-20 degrees) visual fields in healthy groups of young and old emmetropes. Methods. We have measured off-axis aberrations in the groups of 30 younger (24 +/- 3 years) and 30 older (58 +/- 5 years) emmetropes. The aberrations of OD were measured using the COAS-HD VR Shack-Hartmann aberrometer in 10 degrees steps to +/- 40 degrees horizontally and -20 degrees inferiorly in the visual field. The aberrations were quantified with Zernike polynomials for a 4 mm pupil diameter. The second-order aberration coefficients were converted to their respective refraction components (M, J(45), and J(180)). Mixed between-within subjects, analysis of variance were used to determine whether there were significant differences in the refraction and aberration components for the between-subjects variable age and the within-subjects variable eccentricity. Results. Peripheral refraction components were similar in both age groups. Among the higher order coefficients, horizontal coma (C(3)(1)) and spherical aberration (C(4)(0)) varied mostly between the groups. Coma increased linearly with eccentricity, at a more rapid rate in the older group than in the younger group. Spherical aberration was more positive in the older group compared with the younger group. Higher order root mean square increased more rapidly with eccentricity in the older group. Conclusions. Like the axial higher order aberrations, the peripheral higher order aberrations of emmetropes increase with age, particularly coma and spherical aberration.

  • 227.
    Bass, Tarek
    KTH, Skolan för bioteknologi (BIO), Proteinteknologi.
    Affibody molecules targeting HER3 for cancer therapy2017Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    The development of targeted therapy has contributed tremendously to the treatment of patients with cancer. The use of highly specific affinity proteins to target cancer cells has become a standard in treatment strategies for several different cancers. In light of this, many cancer cell markers are investigated for their potential use in diagnostics and therapy. One such marker is the human epidermal growth factor receptor 3, HER3. It has been established as an important contributor to many cancer types. The function of HER3 is to relay cell growth signals from outside of the cell to the inside. Interfering with- and inhibit- ing the function of HER3 has emerged as an interesting strategy for cancer therapeutics. The studies presented in this thesis aim to target HER3 with small, engineered affinity domain proteins for therapeutic purposes. Monomeric affibody molecules have previously been engineered to bind and inhibit HER3 in vitro. Due to the relatively low expression of HER3, an increase in valency appears promising to strengthen the therapeutic potential. Affibody molecules targeting the receptor were thus linked to form bivalent and bispecific constructs and evaluated both in vitro and in vivo. In the first study of this thesis affibody molecules specific for HER3 and HER2 were fused to an albumin binding domain to form bivalent and bispecific construct. The constructs inhibited ligand-induced receptor phos- phorylation of both HER2 and HER3 more efficiently than monomeric affibody molecules. A second approach to enhance the potential of affibody molecules in tumor targeting is described in the second study, where monomeric HER3-binding affibody molecules were engineered to increase their affinity for HER3. The resulting variants showed a 20-fold in- creased affinity and higher capacity to inhibit cancer cell growth. Combining the findings of the first two studies, the third study describes the evaluation of a HER3-targeting bivalent affibody construct for potential application as a therapeutic. Here, the bivalent construct inhibited cancer cell growth in vitro and was found to slow down tumor growth in mice, while being well tolerated and showing no visible toxicity. The fourth study built upon these findings and compares a very similar bivalent construct to the clinically-investigated HER3-specific monoclonal antibody seribantumab. The affibody construct showed very comparable efficacy with the antibody in terms of decreasing tumor growth rate and ex- tending mouse survival. Collectively, these works describe for the first time the use of alternative affinity protein constructs with therapeutic potential targeting HER3.

  • 228.
    Bass, Tarek
    KTH, Skolan för bioteknologi (BIO), Proteinteknologi.
    Evaluating the therapeutic potential of a dimeric HER3-binding affibody construct in comparison with a monoclonal antibody, seribantumab.Manuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    A number of monoclonal antibodies targeting HER3 are currently under clinical investigation as potential cancer therapeutics. We have earlier generated high affinity (low picomolar) affibody molecules targeting HER3. These are small, 58 amino acid, non-immunoglobulin based scaffold proteins that have proved suitable for tumor targeting applications, previously primarily for molecular imaging purposes. Our high affinity HER3-binding affibody molecule has demonstrated to have anti-proliferative capacity on HER3-positive tumor cells. When formatted as a bivalent construct, in which the two affibody moieties are flanking a small albumin-binding domain (ABD), we have recently demonstrated that tumor growth could be delayed in mice for HER3-positive xenografts. In this study, we have modified the construct further and reduced the size. In a comparative study, we evaluated safety, the capacity to delay tumor growth in mice with BxPC-3 xenografts, and mouse survival. Our novel construct was compared to the HER3-specific monoclonal antibody seribantumab (MM-121), presently in clinical development. They were found to be equally potent in their therapeutic effects and in their safety profile. We conclude that this format of bivalent HER3-binding affibody molecules seems promising for further evaluation as candidate therapeutics for treatment of HER3-overexpressing tumors.

  • 229.
    Batool, Nazre
    KTH, Skolan för teknik och hälsa (STH).
    Detection and Spatial Analysis of Hepatic Steatosis in Histopathology Images using Sparse Linear Models2016Inngår i: 2016 SIXTH INTERNATIONAL CONFERENCE ON IMAGE PROCESSING THEORY, TOOLS AND APPLICATIONS (IPTA), IEEE, 2016Konferansepaper (Fagfellevurdert)
    Abstract [en]

    Hepatic steatosis is a defining feature of nonalcoholic fatty liver disease, emerging with the increasing incidence of obesity and metabolic syndrome. The research in image-based analysis of hepatic steatosis mostly focuses on the quantification of fat in biopsy images. This work furthers the image-based analysis of hepatic steatosis by exploring the spatial characteristics of fat globules in whole slide biopsy images after performing fat detection. An algorithm based on morphological filtering and sparse linear models is presented for fat detection. Then the spatial properties of detected fat globules in relation to the hepatic anatomical structures of central veins and portal tracts are explored. The test dataset consists of 38 high resolution images from 21 patients. The experimental results provide an insight into the size distributions of fat globules and their location with respect to the anatomical structures.

  • 230. Bauer, M.
    et al.
    Mazza, E.
    Nava, A.
    Zeck, W.
    Eder, M.
    Bajka, M.
    Cacho, F.
    Lang, U.
    Holzapfel, Gerhard A.
    KTH, Skolan för teknikvetenskap (SCI), Hållfasthetslära (Inst.). Graz University of Technology, Austria.
    In vivo characterization of the mechanics of human uterine cervices2007Inngår i: Reproductive Biomechanics, Blackwell Publishing, 2007, s. 186-202Konferansepaper (Fagfellevurdert)
    Abstract [en]

    The uterine cervix has to provide mechanical resistance to ensure a normal development of the fetus. This is guaranteed by the composition of its extracellular matrix, which functions as a fiber-reinforced composite. At term a complex remodeling process allows the cervical canal to open for birth. This remodeling is achieved by changes in the quality and quantity of collagen fibers and ground substance and their interplay, which influences the biomechanical behavior of the cervix but also contributes to pathologic conditions such as cervical incompetence (CI). We start by reviewing the anatomy and histological composition of the human cervix, and discuss its physiologic function and pathologic condition in pregnancy including biomechanical aspects. Established diagnostic methods on the cervix (palpation, endovaginal ultrasound) used in clinics as well as methods for assessment of cervical consistency (light-induced fluorescence, electrical current, and impedance) are discussed. We show the first clinical application of an aspiration device, which allows in vivo testing of the biomechanical properties of the cervix with the aim to establish the physiological biomechanical changes throughout gestation and to detect pregnant women at risk for CI. In a pilot study on nonpregnant cervices before and after hysterectomy we found no considerable difference in the biomechanical response between in vivo and ex vivo. An outlook on further clinical applications during pregnancy is presented.

  • 231.
    Bauer, Margit
    et al.
    Med Univ Graz, Dept Obstet & Gynecol, Graz, Austria..
    Mazza, Edoardo
    Swiss Fed Inst Technol, Dept Mech & Proc Engn, Zurich, Switzerland..
    Jabareen, Mahmood
    Swiss Fed Inst Technol, Dept Mech & Proc Engn, Zurich, Switzerland..
    Sultan, Leila
    Univ Zurich Hosp, Dept Obstet & Gynecol, CH-8091 Zurich, Switzerland..
    Bajka, Michael
    Univ Zurich Hosp, Dept Obstet & Gynecol, CH-8091 Zurich, Switzerland..
    Lang, Uwe
    Med Univ Graz, Dept Obstet & Gynecol, Graz, Austria..
    Zimmermann, Roland
    Univ Zurich Hosp, Dept Obstet & Gynecol, CH-8091 Zurich, Switzerland..
    Holzapfel, Gerhard A.
    KTH, Skolan för elektro- och systemteknik (EES).
    In Vivo Biomechanical Testing of the Human Uterine Cervix in Pregnancy Using an Aspiration Device2009Inngår i: Reproductive Sciences, ISSN 1933-7191, E-ISSN 1933-7205, Vol. 16, nr 3, s. 197A-197AArtikkel i tidsskrift (Annet vitenskapelig)
  • 232.
    Baumann, Martin J.
    KTH, Skolan för bioteknologi (BIO).
    Xyloglucan-active enzymes: properties, structures and applications2007Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [sv]

    Cellulosabaserade material är världens rikligast förekommande förnyelsebara råvara. Växters cellväggar är naturliga kompositmaterial där den kristallina cellulosan är inbäddad i en väv av hemicellulosa, strukturproteiner och lignin. Xyloglukaner är en viktig hemicellulosagrupp som omger och korslänkar den kristallina cellulosan i cellväggarna. I denna avhandling undersöks undersöks sambanden mellan struktur och funktion hos olika xyloglukan-aktiva enzymer.

    En modell för effektiv enzymatisk omvandling av biomassa ges av cellulosomen hos den anaeroba prokaryota organismen Clostridium thermocellum. Cellulosomen är ett proteinkomplex med hög molmassa och flera olika enzymaktiviteter, bl.a. det inverterande xyloglukan-endohydrolaset CtXGH74A. Proteinstrukturen för CtXGH74A har lösts i komplex med xyloglukanoligosackarider, som stabliliserar vissa loopar/slingor som är oordnade i apostrukturen. Ytterligare detaljerade kinetiska och produktananalyser har genomförts för att entydigt visa att CtXGH74A är ett endoxyloglukanas vars slutliga nedbrytningsprodukt är Glc4-baserade xyloglukanoligosackarider.

    Som jämförelse innehåller glykosidhydrolasfamilj 16 (GH16) såväl hydrolytiska endoxyloglukanaser som xyloglukantransglykosylaser (XETs) från växter. För att utreda vad som bestämmer förhållandet mellan transglykosylering och hydrolys i xyloglukanaktiva enzymer från familj GH 16 jämfördes struktur och kinetik hos ett strikt transglykosylas, PttXET16-34 från hybridasp, med ett nära besläktat hydrolytiskt enzym, NXG1 från krasse. I NXG1 identifierades en viktig förlängningsloop, som vid trunkering gav ett muterat enzym med högre transglykosyleringshastighet och minskad hydrolytisk aktivitet. Kinetikstudierna genomfördes med hjälp av nyutvecklade känsliga provmetoder med väldefinerade XGO:er och ett antal kromogena XGO-arylglykosider.

    En detaljerad förståelse av enzymologin inom GH16 möjliggjorde utvecklingen av en ny kemoenzymatisk metod för biomimetisk fiberytmodifiering med hjälp av PttXET16-34s translgykosyleringsaktivitet. Aminoalditolderivat av xyloglukanoligosackarider användes som nyckelintermediärer för att introducera ny kemisk funktionalitet hos xyloglukan, såsom kromoforer, reaktiva grupper, proteinligander och initiatorer för polymeriseringsreaktioner. Tekniken innebär ett nytt och mångsidigt verktyg för fiberytmodifiering.

  • 233.
    Baxter, Brent S.
    et al.
    University of Utah.
    Hitchner, Lewis E.
    University of Utah.
    Maguire Jr., Gerald Q.
    Columbia University.
    A standard format for digital image exchange1982Bok (Annet vitenskapelig)
  • 234.
    Baxter, Brent S.
    et al.
    University of Utah.
    Zeleznik, Michael P.
    Maguire Jr., Gerald Q.
    Columbia University, Department of Computer Science.
    What Types of Standards would be useful in PACS Activities1983Inngår i: Proceedings of the Society of Photo-Optical Instrumentation Engineers, ISSN 0361-0748, Vol. 418, s. 146-150Artikkel i tidsskrift (Fagfellevurdert)
  • 235.
    Beaussant Törne, Karin
    et al.
    KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik.
    Khan, Fareed Ashraf
    Örnberg, A.
    Weissenrieder, Jonas
    KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik.
    Zn-Mg and Zn-Ag degradation mechanism under biologically relevant conditionsManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    Zinc alloys form a promising new class of biodegradable metals that combine suitable mechanical properties with the favorable degradation properties of pure zinc. However, the current understanding of the influence of alloying elements on the corrosion of zinc alloys, in biologically relevant media, is limited. We studied the degradation of three alloys, Zn 4 wt% Ag, Zn 0.5 wt% Mg and Zn 3 wt% Mg by in situ electrochemical impedance spectroscopy (EIS). After exposure for 1h or 30 days the samples were characterized by infrared spectroscopy and scanning electron microscopy (SEM). The presence of secondary phases in the alloy microstructure induced selective corrosion and increased degradation rate. An increase in surface inhomogeneity was evident by EIS analysis both at short (hours) as well as long immersion times (days). The microgalvanic corrosion of the Zn-Ag alloy resulted in enrichment of the AgZn3 phase at the sample surface. The enrichment of Ag and potential release of AgZn3 particles may result in complications during the tissue regeneration. The Zn-Mg alloy surface was depleted of the Mg-rich phase after 8-12 days. The selective dissolution caused local precipitation of2corrosion products and a thicker corrosion layer with larger pore size consistent with increased corrosion rate.

  • 236.
    Beaussant Törne, Karin
    et al.
    KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik.
    Örnberg, A.
    Weissenrieder, Jonas
    KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik.
    Characterization of the Protective Layer Formed on Zinc in Whole BloodManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    The advantageous degradation properties of zinc in a biological environment are related to the presence of a protective corrosion layer composed of both organic and inorganic components. However, the mechanisms governing its formation and how the organic species influence its properties have not been established. Here we study the protective layer formation during anodic polarization in whole blood by in situ electrochemical impedance spectroscopy (EIS) as well as infrared spectroscopy and scanning electron microscopy. Simulated body fluid (m-SBF) was used as a reference media to discern the influence of the organic species present in whole blood. Protective zinc phosphate layers form on the Zn surface in both solutions, but of different nature and through diverse mechanisms. In m-SBF the passivating thin film formation occur already at open circuit potential, reducing the corrosion current compared to exposure in whole blood by a factor of 103. The high corrosion current in whole blood can be explained by a process including rapid protein adsorption preventing the initial formation of a protective phosphate layer. EIS analysis detected an inductive arc in whole blood at low overpotentials, before the onset of protective film formation, indicating the presence of adsorbed Zn2ions. The coverage of Zn ions approach 100% of the active surface at 110 mV. At this critical surface coverage a reaction between the adsorbed Zn ions and PO42- takes place which results in formation of a protective, porous, film of ~1 μm thickness. The inorganic component of the protective film formed in whole blood was characterized as Zn(PO4)2(OH)2·3H2O.

  • 237.
    Beckman, Claes
    KTH, Skolan för informations- och kommunikationsteknik (ICT), Centra, KTH Center för Trådlösa System, Wireless@kth. KTH, Skolan för informations- och kommunikationsteknik (ICT), Kommunikationssystem, CoS.
    Comparison of three methods of evaluating glare.1992Inngår i: Acta ophthalmologica, ISSN 0001-639X, Vol. 70, nr 1, s. 53-9Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A Humphrey Automatic Refractor Model 570 was used to measure the impairment of visual acuity for low contrast optotypes as a result of glare for normal subjects and for subjects with cataracts. This was compared with a direct measure of intraocular light scatter as measured by a compensating technique and with a subjective assessment of glare determined by a questionnaire. Only a weak correlation (r = 0.28) was found between the decrease in low contrast letter acuity and intraocular light scatter. The subjective assessment of glare sensitivity was not correlated with the decrease in low contrast letter acuity, but correlated to some extent (r = 0.55) with the measurement of intraocular light scatter.

  • 238.
    Beckman, Claes
    KTH, Skolan för informations- och kommunikationsteknik (ICT), Centra, KTH Center för Trådlösa System, Wireless@kth. KTH, Skolan för informations- och kommunikationsteknik (ICT), Kommunikationssystem, CoS.
    Glare and contrast sensitivity before and after Nd: YAG laser capsulotomy.1994Inngår i: Acta ophthalmologica, ISSN 0001-639X, Vol. 72, nr 1, s. 27-32Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The benefits of Nd:YAG laser capsulotomy on visual performance were evaluated in 13 patients with after-cataract following extracapsular cataract extraction. Besides clinical evaluation we measured: visual acuity, letter contrast sensitivity with and without the presence of a circular glare source (glare angle: 8 degrees). Finally, the patients were asked to evaluate their subjective glare problems. In all patients, visual acuity had decreased markedly compared to measurements 2 months after cataract surgery. Before capsulotomy we observed impaired letter contrast sensitivity and increased intraocular light scatter compared to normals. Following capsulotomy, VA and contrast sensitivity both improved by a factor of 2. The subjective glare problems diminished, although most patients showed minor decreases in intraocular light scatter. The limited glare induced loss of letter contrast sensitivity, present before capsulotomy, remained after treatment. Our study indicates that after-cataract impairs resolution and contrast sensitivity without necessarily causing a marked increase in light scatter as measured at a large angle.

  • 239.
    Beckman, Claes
    KTH, Skolan för informations- och kommunikationsteknik (ICT), Centra, KTH Center för Trådlösa System, Wireless@kth. KTH, Skolan för informations- och kommunikationsteknik (ICT), Kommunikationssystem, CoS.
    Glare measurements before and after cataract surgery.1993Inngår i: Acta ophthalmologica, ISSN 0001-639X, Vol. 71, nr 4, s. 471-6Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The efficacy of cataract surgery in improving visual performance was evaluated in 10 patients by measuring changes in intraocular light scatter, contrast sensitivity and glare induced visual loss. Two different methods were used to estimate these functions before and after cataract extraction with implantation of a monofocal posterior intraocular lens. By one method intraocular light scattering was assessed. By the other, letter contrast sensitivity and glare induced visual loss were determined. Preoperatively most patients had various glare problems, glare induced visual loss and increased intraocular light scatter. Following surgery the letter contrast sensitivity increased by a factor of 3 or more (mean 4.3). The glare problems diminished or disappeared after surgery, although several patients still had increased intraocular light scattering and glare induced visual loss compared to normals. Postoperatively the contrast sensitivity both with and without glare had increased to a level where the glare induced visual loss did not create any visual problems.

  • 240.
    Beckman, Claes
    University of Waterloo.
    The influence of increased interocular lightscatter on the contrast in a confocal scanning laserophthalmoscope image1995Inngår i: Vision Science and Its Application, Vol. 1 of 1995 OSA Technical Digest Series (Optical Society of America, 1995) / [ed] Optical Society of America, Washington, 1995, Vol. 1, s. 106-109Konferansepaper (Fagfellevurdert)
    Abstract [en]

    the influence of increased intraocular light scatter on image quality in a confocal scanning laserophthalmoscope (CSLO) is quntified through computer simulations and model eye experiments.

  • 241.
    Beckman, Claes
    KTH, Skolan för informations- och kommunikationsteknik (ICT), Centra, KTH Center för Trådlösa System, Wireless@kth. KTH, Skolan för informations- och kommunikationsteknik (ICT), Kommunikationssystem, CoS.
    The 'light scattering factor'. Importance of stimulus geometry, contrast definition, and adaptation.1995Inngår i: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 36, nr 11, s. 2313-7Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    PURPOSE: Paulsson and Sjöstrand have suggested that the light scattering factor (LSF) can be estimated by using the equation: LSF = L/E (M2/M1-1). Here L is the space average luminance of the target, E is the illuminance of the glare source, and M2 and M1 are modulation contrast thresholds in the presence and absence of the glare source. To compensate for change of adaptation. Abrahamsson and Sjöstrand later modified the above equation by introducing a correction factor (CF): LSF = L/E ((CF) (M2/M1-1). The purpose of this study is to analyze the validity of the above equations.

    METHODS: The importance of stimulus geometry, contrast definition, background luminance, and glare illumination is studied through theoretical analysis and comparison with earlier studies. Stimulus geometry and contrast definition are studied through optical modeling. Adaptation is modeled according to the laws of Weber and DeVries-Rose.

    RESULTS: The choice of contrast definition may corrupt the result by a factor of 2. At background luminance levels above approximately 10 cd/m2, the Paulsson-Sjöstrand equation agrees well with theory. At lower background levels, the Abrahamsson-Sjöstrand equation is used with correction factors derived from adaptation measurements. Using this equation and earlier published data from glare testing performed at 2 cd/m2, the results are found to be in fair agreement with the light scattering theory.

    CONCLUSIONS: Glare testing using the Paulsson-Sjöstrand equation is found to be valid as long as the measurements are performed at high luminance levels (above 10 cd/m2), with targets of low spatiotemporal frequencies (e.g., 2 cpd and 1 Hz) and with the use of a properly chosen definition of contrast. At lower luminance levels, the Abrahamsson-Sjöstrand equation may be used with well-derived correction factors.

  • 242. Beckman, Claes
    et al.
    Jörgen, Thaung
    Göteborgs Universitet.
    Johan, Sjöstrand
    Göteborgs Universitet.
    In vitro Lens Scatter Measurements and Glare Testing1994Inngår i: The Association for Research in Vision and Ophthalmology Annual Meeting. Sarasota, Florida, May 1-6, 1994. Abstracts. Investigative Ophthalmology & Visual Science March 1994, Vol.35, 1254-2383., 1994, Vol. 35, s. 1803-Konferansepaper (Fagfellevurdert)
  • 243. Beckman, Claes
    et al.
    Sjöstrand, J
    Confocal fundus imaging with a scanning laser ophthalmoscope in eyes with cataract.1995Inngår i: British Journal of Ophthalmology, ISSN 0007-1161, E-ISSN 1468-2079, Vol. 79, nr 10, s. 900-4Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    AIMS/BACKGROUND: The study aimed to determine the influence of increased intraocular light scatter on the contrast in scanning laser ophthalmoscope (SLO) images and to examine to what extent SLO images can visualise the fundus through media opacities due to cataract.

    METHODS: Intraocular light scatter was estimated from measurements of letter contrast sensitivity before and after cataract surgery in five eyes. SLO images were obtained before and after surgery using confocal apertures of 1, 2, 4, and 10 mm, at laser wavelengths of 633 and 780 nm. Visibility of the fundus was determined by measurements of retinal contrast. SLO images were compared with standard fundus photographs.

    RESULTS: SLO images obtained before surgery revealed details of the retina that were unresolvable in the fundus photographs because of light scattering. By using one of the three smallest apertures, image contrast was further improved. However, no simple relations between aperture size, estimated light scatter, and image contrast could be found.

    CONCLUSION: SLO imaging was found to be superior to fundus photography for viewing the retina in eyes with cataract. Owing to the inhomogeneous nature of cataracts, the optimal choice of confocal aperture and laser wavelength is not simple and must be individualised.

  • 244.
    Beckman, Claes
    et al.
    KTH, Skolan för informations- och kommunikationsteknik (ICT), Centra, KTH Center för Trådlösa System, Wireless@kth. KTH, Skolan för informations- och kommunikationsteknik (ICT), Kommunikationssystem, CoS.
    Thaung, Jörgen
    Sjöstrand, Johan
    In-vitro lens scatter measurements and glare testing1994Konferansepaper (Annet vitenskapelig)
  • 245.
    Bedri, Sahl Khalid
    et al.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.;Karolinska Inst, Ctr Mol Med, Stockholm, Sweden..
    Nilsson, Ola B.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.;Karolinska Inst, Ctr Mol Med, Stockholm, Sweden.;Advice Foretagsassistans & Stockholm AB, TCER AB, Stockholm, Sweden..
    Fink, Katharina
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.;Karolinska Inst, Ctr Mol Med, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Neurol, Stockholm, Sweden..
    Månberg, Anna
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinity Proteomics. KTH Royal Inst Technol, Sch Engn Sci Chem Biotechnol & Hlth, Affin Prote, SciLifeLab, Stockholm, Sweden..
    Hamsten, Carl
    Karolinska Inst, Dept Med, Immunol & Allergy Unit, Stockholm, Sweden..
    Ayoglu, Burcu
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinity Proteomics. KTH Royal Inst Technol, Sch Engn Sci Chem Biotechnol & Hlth, Affin Prote, SciLifeLab, Stockholm, Sweden..
    Manouchehrinia, Ali
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.;Karolinska Inst, Ctr Mol Med, Stockholm, Sweden..
    Nilsson, Peter
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinity Proteomics. KTH Royal Inst Technol, Sch Engn Sci Chem Biotechnol & Hlth, Affin Prote, SciLifeLab, Stockholm, Sweden..
    Olsson, Tomas
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.;Karolinska Inst, Ctr Mol Med, Stockholm, Sweden..
    Hillert, Jan
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.;Karolinska Inst, Ctr Mol Med, Stockholm, Sweden..
    Grönlund, Hans
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.;Karolinska Inst, Ctr Mol Med, Stockholm, Sweden..
    Glaser, Anna
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.;Karolinska Inst, Ctr Mol Med, Stockholm, Sweden..
    Plasma protein profiling reveals candidate biomarkers for multiple sclerosis treatment2019Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 14, nr 5, artikkel-id e0217208Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Multiple sclerosis (MS) treatment options have improved significantly over the past decades, but the consequences of MS can still be devastating and the needs for monitoring treatment surveillance are considerable. In the current study we used affinity proteomics technology to identify potential biomarkers which could ultimately be used to as facilitate treatment decisions. We profiled the intra-individual changes in the levels of 59 target proteins using an antibody suspension bead array in serial plasma samples from 44 MS patients during treatment with natalizumab followed by fingolimod. Nine proteins showed decreasing plasma levels during natalizumab treatment, with PEBP1 and RTN3 displaying the most significant changes. Protein levels remained stable during fingolimod treatment for both proteins. The decreasing PEBP1 levels during natalizumab treatment could be validated using ELISA and replicated in an independent cohort. These results support the use of this technology as a high throughput method of identifying potentially useful biomarkers of MS treatment.

  • 246. Beillas, Philippe
    et al.
    Giordano, Chiara
    Alvarez, Victor
    Li, Xiaogai
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Medicinteknik och hälsosystem, Neuronik.
    Ying, Xingjia
    Chevalier, Marie-Christine
    Kirscht, Stefan
    Kleiven, Svein
    Development and performance of the PIPER scalable child human body models2016Inngår i: 14th International Conference on the Protection of Children in Cars, 2016Konferansepaper (Fagfellevurdert)
  • 247.
    Bekkouche, Bo
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsvetenskap och beräkningsteknik (CST). KTH.
    Classification of Neuronal Subtypes in the Striatum and the Effect of Neuronal Heterogeneity on the Activity Dynamics2016Independent thesis Advanced level (degree of Master (Two Years)), 20 poäng / 30 hpOppgave
    Abstract [en]

    Clustering of single-cell RNA sequencing data is often used to show what states and subtypes cells have. Using this technique, striatal cells were clustered into subtypes using different clustering algorithms. Previously known subtypes were confirmed and new subtypes were found. One of them is a third medium spiny neuron subtype. Using the observed heterogeneity, as a second task, this project questions whether or not differences in individual neurons have an impact on the network dynamics. By clustering spiking activity from a neural network model, inconclusive results were found. Both algorithms indicating low heterogeneity, but by altering the quantity of a subtype between a low and high number, and clustering the network activity in each case, results indicate that there is an increase in the heterogeneity. This project shows a list of potential striatal subtypes and gives reasons to keep giving attention to biologically observed heterogeneity.

  • 248.
    Belic, Jovana
    KTH, Skolan för elektroteknik och datavetenskap (EECS), Beräkningsvetenskap och beräkningsteknik (CST).
    Untangling Cortico-Striatal Circuitry and its Role in Health and Disease - A computational investigation2018Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    The basal ganglia (BG) play a critical role in a variety of regular motor and cognitive functions. Many brain diseases, such as Parkinson’s diseases, Huntington’s disease and dyskinesia, are directly related to malfunctions of the BG nuclei. One of those nuclei, the input nucleus called the striatum, is heavily connected to the cortex and receives afferents from nearly all cortical areas. The striatum is a recurrent inhibitory network that contains several distinct cell types. About 95% of neurons in the striatum are medium spiny neurons (MSNs) that form the only output from the striatum. Two of the most examined sources of GABAergic inhibition into MSNs are the feedback inhibition (FB) from the axon collaterals of the MSNs themselves, and the feedforward inhibition (FF) via the small population (1-2% of striatal neurons) of fast spiking interneurons (FSIs). The cortex sends direct projections to the striatum, while the striatum can affect the cortex only indirectly through other BG nuclei and the thalamus. Understanding how different components of the striatal network interact with each other and influence the striatal response to cortical inputs has crucial importance for clarifying the overall functions and dysfunctions of the BG.

        In this thesis I have employed advanced experimental data analysis techniques as well as computational modelling, to study the complex nature of cortico-striatal interactions. I found that for pathological states, such as Parkinson’s disease and L-DOPA-induced dyskinesia, effective connectivity is bidirectional with an accent on the striatal influence on the cortex. Interestingly, in the case of L-DOPA-induced dyskinesia, there was a high increase in effective connectivity at ~80 Hz and the results also showed a large relative decrease in the modulation of the local field potential amplitude (recorded in the primary motor cortex and sensorimotor striatum in awake, freely behaving, 6-OHDA lesioned hemi-parkinsonian rats) at ~80 Hz by the phase of low frequency oscillations. These results suggest a lack of coupling between the low frequency activity of a presumably larger neuronal population and the synchronized activity of a presumably smaller group of neurons active at 80 Hz.

        Next, I used a spiking neuron network model of the striatum to isolate the mechanisms underlying the transmission of cortical oscillations to the MSN population. I showed that FSIs play a crucial role in efficient propagation of cortical oscillations to the MSNs that did not receive direct cortical oscillations. Further, I have identified multiple factors such as the number of activated neurons, ongoing activity, connectivity, and synchronicity of inputs that influenced the transfer of oscillations by modifying the levels of FB and FF inhibitions. Overall, these findings reveal a new role of FSIs in modulating the transfer of information from the cortex to striatum. By modulating the activity and properties of the FSIs, striatal oscillations can be controlled very efficiently. Finally, I explored the interactions in the striatal network with different oscillation frequencies and showed that the features of those oscillations, such as amplitude and frequency fluctuations, can be influenced by a change in the input intensities into MSNs and FSIs and that these fluctuations are also highly dependent on the selected frequencies in addition to the phase offset between different cortical inputs.

        Lastly, I investigated how the striatum responds to cortical neuronal avalanches. Recordings in the striatum revealed that striatal activity was also characterized by spatiotemporal clusters that followed a power law distribution albeit, with significantly steeper slope. In this study, an abstract computational model was developed to elucidate the influence of intrastriatal inhibition and cortico-striatal interplay as important factors to understand the experimental findings. I showed that one particularly high activation threshold of striatal nodes can reproduce a power law-like distribution with a coefficient similar to the one found experimentally. By changing the ratio of excitation and inhibition in the cortical model, I saw that increased activity in the cortex strongly influenced striatal dynamics, which was reflected in a less negative slope of cluster size distributions in the striatum.  Finally, when inhibition was added to the model, cluster size distributions had a prominently earlier deviation from the power law distribution compared to the case when inhibition was not present. 

  • 249.
    Belic, Jovana
    et al.
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsvetenskap och beräkningsteknik (CST). KTH, Centra, Science for Life Laboratory, SciLifeLab. Bernstein Center Freiburg, University of Freiburg, Freiburg, Germany.
    Halje, Pär
    Lund University.
    Richter, Ulrike
    Lund University.
    Per, Petersson
    Lund University.
    Hellgren Kotaleski, Jeanette
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsvetenskap och beräkningsteknik (CST). Department of Neuroscience, Karolinska Institute, Stockholm, Sweden.
    Untangling cortico-striatal connectivity and cross-frequency coupling in L-DOPA-induced dyskinesia2016Inngår i: Frontiers in Systems Neuroscience, ISSN 1662-5137, E-ISSN 1662-5137, Vol. 10, nr 26, s. 1-12Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We simultaneously recorded local field potentials in the primary motor cortex and sensorimotor striatum in awake, freely behaving, 6-OHDA lesioned hemi-parkinsonian rats in order to study the features directly related to pathological states such as parkinsonian state and levodopa-induced dyskinesia. We analysed the spectral characteristics of the obtained signals and observed that during dyskinesia the most prominent feature was a relative power increase in the high gamma frequency range at around 80 Hz, while for the parkinsonian state it was in the beta frequency range. Here we show that during both pathological states effective connectivity in terms of Granger causality is bidirectional with an accent on the striatal influence on the cortex. In the case of dyskinesia, we also found a high increase in effective connectivity at 80 Hz. In order to further understand the 80- Hz phenomenon, we performed cross-frequency analysis and observed characteristic patterns in the case of dyskinesia but not in the case of the parkinsonian state or the healthy state. We noted a large decrease in the modulation of the amplitude at 80 Hz by the phase of low frequency oscillations (up to ~10 Hz) across both structures in the case of dyskinesia. This may suggest a lack of coupling between the low frequency activity of the recorded network and the group of neurons active at ~80 Hz.

  • 250.
    Belic, Jovana
    et al.
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB. University of Freiburg, Germany.
    Halje, Pär
    Lund University.
    Richter, Ulrike
    Lund University.
    Petersson, Per
    Lund Unversity.
    Hellgren Kotaleski, Jeanette
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB. Karolinska Institutet, Sweden.
    Corticostriatal circuits and their role in disease2015Inngår i: Frontiers in Neuroscience, ISSN 1662-4548, E-ISSN 1662-453X, Vol. 8, s. 31-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The basal ganglia (BG) represent subcortical structures considered to be involved in action selection and decision making [1]. Dysfunction of the BG circuitry leads to many motor and cognitive disorders such as Parkinson’s disease (PD), Tourette syndrome, Huntington’s disease, obsessive compulsive disorder and many others. Therefore, we simultaneously recorded local field potentials (LFPs) in primary motor cortex and sensorimotor striatum to study features directly related to healthy versus pathological states such as Parkinson disease and levodopa-induced dyskinesia [2], [3]. The striatum, the input stage of the basal ganglia (BG), is an inhibitory network that contains several distinct cell types and receives massive excitatory inputs from the cortex. Cortex sends direct projections to the striatum, while striatum can affect cortex only indirectly through other BG nuclei and thalamus. Firstly we analyzed spectral characteristics of the obtained signals and observed that during dyskinesia, the most prominent feature was a relative power increase in the high gamma frequency range around 80 Hz, while for PD it was the beta frequency range. Secondly our preliminary results have shown that during both pathological states effective connectivity in terms of Granger causality is bidirectional with an accent on striatal influence on cortex. In the case of dyskinesia we have also found a specifically high increase in effective connectivity at 80 Hz. In order to further understand the 80-Hz phenomenon we have performed cross-frequency analysis across all states and both structures and observed characteristic patterns in the case of dyskinesia in both structures but not in the case of PD and healthy state. We have seen a large relative decrease in the modulation of the amplitude at 80Hz by the phase of low frequency oscillations (up to ~10Hz). It has been suggested that the activity of local neural populations is modulated according to the global neuronal dynamics in the way that populations oscillate and synchronize at lower frequencies and smaller ensembles are active at higher frequencies Our results suggest unexpectedly a lack of coupling between the low frequency activity of a larger population and the synchronized activity of a smaller group of neurons active at 80Hz.

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