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  • 151.
    Antonsson Lundberg, Ann-Beth
    et al.
    KTH, Skolan för teknik och hälsa (STH), Ergonomi.
    Nyman, Teresia
    KI, Institutionen för folkhälsovetenskap.
    Education for Occupational health service professionals in different countries2011Konferansepaper (Annet vitenskapelig)
  • 152.
    Antonsson Lundberg, Ann-Beth
    et al.
    KTH, Skolan för teknik och hälsa (STH), Ergonomi.
    Schmidt, L
    Swedish Occupational Health Services and Small Enterprises: How does it work?2005Inngår i: OHS2005 Conference Proceedings: SJWEH Supplements 2005; no 1, 2005Konferansepaper (Annet vitenskapelig)
  • 153.
    Antonsson Lundberg, Ann-Beth
    et al.
    KTH, Skolan för teknik och hälsa (STH), Ergonomi.
    Verschoor, Atie H
    Ild care foundation, Maastricht.
    General Purpose of WE-LCA2004Inngår i: Working Environment in Life-Cycle Assessment / [ed] Poulsen, Jensen, Antonsson, Bengtsson, Karling, Schmidt, Brekke, Becker, Verschoor, Society of Environmental Toxicology and Chemistry (SETAC), 2004Kapittel i bok, del av antologi (Annet (populærvitenskap, debatt, mm))
  • 154. Apellaniz-Ruiz, Maria
    et al.
    Sanchez-Barroso, Lara
    Gutierrez-Gutierrez, Gerardo
    Sereno, Maria
    Garcia-Donas, Jesus
    Avall-Lundqvist, Elisabeth
    Green, Henrik
    KTH, Skolan för bioteknologi (BIO), Genteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Brosen, Kim
    Bergmann, Troels K.
    Rodriguez-Antona, Cristina
    Replication of Genetic Polymorphisms Reported to Be Associated with Taxane-Related Sensory Neuropathy in Patients with Early Breast Cancer Treated with Paclitaxel-Letter2015Inngår i: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 21, nr 13, s. 3092-3093Artikkel i tidsskrift (Fagfellevurdert)
  • 155. Appelberg, J.
    et al.
    Janson, C.
    Lindberg, E.
    Pavlenko, Tatjana
    Department of Statistics, Stockholm University, Stockholm, Sweden.
    Hedenstierna, G.
    Lung aeration during sleep in patients with obstructive sleep apnoea2010Inngår i: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 30, nr 4, s. 301-307Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Previous studies have indicated that patients with obstructive sleep apnoea (OSA) have altered ventilation and lung volumes awake and the results suggest that this may be a determinant of severity of desaturations during sleep. However, little is known about regional lung aeration during sleep in patients with OSA. Methods: Twelve patients with OSA were included in the study. Computed tomography was used to study regional lung aeration during wakefulness and sleep. Lung aeration was calculated in ml gas/g lung tissue in four different regions of interest (ROI(1-4)), along the border of the lung from ventral to dorsal. Results: Lung aeration in the dorsal (dependent) lung region (ROI(4)) was lower during sleep compared to wakefulness 0 center dot 78 +/- 0 center dot 19 versus 0 center dot 88 +/- 0 center dot 19 (mean +/- SD) ml gas/g lung tissue (P = 0 center dot 005). Associations were found between awake expiratory reserve volume and change in lung aeration from wakefulness to sleep in ROI(4) (r = -0 center dot 69; P = 0 center dot 012). In addition, the change in lung aeration in the dorsal region correlated to sleep time (r = 0 center dot 69; P = 0 center dot 014) but not to time in supine position. The difference in lung aeration between inspiration and expiration (i.e. ventilation), was larger in the ventral lung region when expressed as ml gas per g lung tissue. In two patients it was noted that, during on-going obstructive apnoea, lung aeration tended to be increased rather than decreased. Conclusions: Aeration in the dorsal lung region is reduced during sleep in patients with OSA. The decrease is related to lung volume awake and to sleep time.

  • 156. Appelberg, Jonas
    et al.
    Pavlenko, Tatjana
    Mid Sweden University.
    Bergman, Henrik
    Rothen, H
    Hedenstierna, Göran
    Lung aeration during sleep2007Inngår i: Chest, ISSN 0012-3692, E-ISSN 1931-3543, Vol. 131, nr 1, s. 122-129Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: During sleep, ventilation and functional residual capacity (FRC) decrease slightly. This study addresses regional lung aeration during wakefulness and sleep. Methods: Ten healthy subjects underwent spirometry awake and with polysomnography, including pulse oximetry, and also CT when awake and during sleep. Lung aeration in different lung regions was analyzed. Another three subjects were studied awake to develop a protocol for dynamic CT scanning during breathing. Results: Aeration in the dorsal, dependent lung region decreased from a mean of 1.14 ± 0.34 mL (± SD) of gas per gram of lung tissue during wakefulness to 1.04 ± 0.29 mL/g during non-rapid eye movement (NREM) sleep (- 9%) [p = 0.034]. In contrast, aeration increased in the most ventral, nondependent lung region, from 3.52 ± 0.77 to 3.73 ± 0.83 mL/g (+ 6%) [p = 0.007]. In one subject studied during rapid eye movement (REM) sleep, aerationdecreased from 0.84 to 0.65 mL/g (- 23%). The fall in dorsal lung aeration during sleepcorrelated to awake FRC (R2 = 0.60; p = 0.008). Airway closure, measured awake, occurred near and sometimes above the FRC level. Ventilation tended to be larger in dependent, dorsal lung regions, both awake and during sleep (upper region vs lower region, 3.8% vs 4.9% awake, p = 0.16, and 4.5% vs 5.5% asleep, p = 0.09, respectively). Conclusions: Aeration is reduced in dependent lung regions and increased in ventral regions during NREM and REM sleep. Ventilation was more uniformly distributed between upper and lower lung regions than has previously been reported in awake, upright subjects. Reduced respiratory muscle tone and airway closure are likely causative factors.

  • 157. Arabi, A.
    et al.
    Ullah, K.
    Branca, R. M. M.
    Johansson, J.
    Bandarra, D.
    Haneklaus, M.
    Fu, J.
    Ariës, I.
    Nilsson, Peter
    KTH, Skolan för bioteknologi (BIO), Proteomik (stängd 20130101). KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Den Boer, M. L.
    Pokrovskaja, K.
    Grandér, D.
    Xiao, G.
    Rocha, S.
    Lehtiö, J.
    Sangfelt, O.
    Proteomic screen reveals Fbw7 as a modulator of the NF-kappa B pathway2012Inngår i: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 3, s. 976-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Fbw7 is a ubiquitin-ligase that targets several oncoproteins for proteolysis, but the full range of Fbw7 substrates is not known. Here we show that by performing quantitative proteomics combined with degron motif searches, we effectively screened for a more complete set of Fbw7 targets. We identify 89 putative Fbw7 substrates, including several disease-associated proteins. The transcription factor NF-κB2 (p100/p52) is one of the candidate Fbw7 substrates. We show that Fbw7 interacts with p100 via a conserved degron and that it promotes degradation of p100 in a GSK3 2 phosphorylation-dependent manner. Fbw7 inactivation increases p100 levels, which in the presence of NF-κB pathway stimuli, leads to increased p52 levels and activity. Accordingly, the apoptotic threshold can be increased by loss of Fbw7 in a p100-dependent manner. In conclusion, Fbw7-mediated destruction of p100 is a regulatory component restricting the response to NF-κB2 pathway stimulation.

  • 158.
    Araújo, Ana Catarina
    et al.
    Univ Lisbon, Lisbon, Portugal .
    Rauter, Amelia P.
    Nicotra, Francesco
    Airoldi, Cristina
    Costa, Barbara
    Cipolla, Laura
    Sugar-Based Enantiomeric and Conformationally Constrained Pyrrolo[2,1-c][1,4]-Benzodiazepines as Potential GABA(A) Ligands2011Inngår i: Journal of Medicinal Chemistry, ISSN 0022-2623, E-ISSN 1520-4804, Vol. 54, nr 5, s. 1266-1275Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Synthesis of a library of pyrrolo[2,1-c][1,4]-benzodiazepines derived from spiro bicyclic D- or L-proline analogues containing a D- or L-fructose moiety was developed. The L-fructose moiety was obtained by using a new synthetic pathway starting from L-arabinose through a six steps synthesis in 18% overall yield. Molecular modeling calculations and DNMR studies showed that D- and L.-fructose-based pyrrolobenzodiazepines exhibit a rigid (P)- and (M)-helical conformation, respectively, in which the C-11a substituent was always pseudoequatorial. Additionally, pyrrolobenzodiazepines functionalized with a chloride, bromide, nitro, or amino group in the benzene ring, with or without N-methylation and with or without protection of sugar alcohol groups, allowed a relationship between the molecular structure and biological activity to be established. The conformation of the diazepam ring was not the sole key player influencing binding affinities, and the sugar moiety can in some cases increase the binding activity, possibly by compounds have increased the understanding of the differential recognition receptor. participating in the binding event. Finally, these of (M)-/(P)-helical benzodiazepines on GABA(A) receptor.

  • 159. Arlinger, S.
    et al.
    Uhlén, I.
    Hagerman, B.
    Kähäri, K.
    Rosenhall, U.
    Spens, Karl Erik
    KTH, Skolan för datavetenskap och kommunikation (CSC), Tal, musik och hörsel, TMH.
    Holgers, K. -M
    Höga ljudnivåer på konserter kan ge hörselskador för livet: Musikbranschen tar inte sitt ansvar2007Inngår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 104, nr 41, s. 2978-2979Artikkel i tidsskrift (Fagfellevurdert)
  • 160. Arlinger, Stig
    et al.
    Nordqvist, Peter
    KTH, Skolan för datavetenskap och kommunikation (CSC), Tal, musik och hörsel, TMH.
    Öberg, Marie
    International Outcome Inventory for Hearing Aids: Data From a Large Swedish Quality Register Database2017Inngår i: American Journal of Audiology, ISSN 1059-0889, E-ISSN 1558-9137, Vol. 26, nr 3, s. 443-450Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose: The purpose of this study was to analyze a database of completed International Outcome Inventory for Hearing Aids (IOI-HA) questionnaires obtained from over 100,000 clients fitted with new hearing aids in Sweden during the period of 2012-2016. Mean IOI-HA total scores were correlated with degree of hearing loss, unilateral versus bilateral fitting, first-time versus return clients, gender, and variation among dispensing clinics. The correlations with expectations, service quality, and technical functioning of the hearing aids were also analyzed. Method: Questionnaires containing the 7 IOI-HA items as well as questions concerning some additional issues were mailed to clients 3-6 months after fitting of new hearing aids. The questionnaires were returned to and analyzed by an independent research institute. Results: More than 100 dispensing clinics nationwide take part in this project. A response rate of 52.6% resulted in 106,631 data sets after excluding incomplete questionnaires. Forty-six percent of the responders were women, and 54% were men. The largest difference in mean score (0.66) was found for the IOI-HA item "use" between return clients and first-time users. Women reported significantly higher (better) scores for the item "impact on others" compared with men. The bilaterally fitted subgroup reported significantly higher scores for all 7 items compared with the unilaterally fitted subgroup. Experienced users produced higher scores on benefit and satisfaction items, whereas first-time users gave higher scores for residual problems. No correlation was found between mean IOI-HA total score and average hearing threshold level (pure-tone average [ PTA]). Mean IOI-HA total scores were found to correlate significantly with perceived service quality of the dispensing center and with the technical functionality of the hearing aids. Conclusions: When comparing mean IOI-HA total scores from different studies or between groups, differences with regard to hearing aid experience, gender, and unilateral versus bilateral fitting have to be considered. No correlation was found between mean IOI-HA total score and degree of hearing loss in terms of PTA. Thus, PTA is not a reliable predictor of benefit and satisfaction of hearing aid provision as represented by the IOI-HA items. Identification of a specific lower fence in PTA for hearing aid candidacy is therefore to be avoided. Large differences were found in mean IOI-HA total scores related to different dispensing centers.

  • 161.
    Arman, Rebecka
    et al.
    Sahlgrenska akademin, Göteborgs universitet.
    Dellve, Lotta
    Sahlgrenska akademin, Göteborgs universitet.
    Wikström, Ewa
    Sahlgrenska akademin, Göteborgs universitet.
    Törnström, Linda
    Sahlgrenska akademin, Göteborgs universitet.
    What health care managers do: Applying Mintzberg’s structured observation method2009Inngår i: Journal of Nursing Management, ISSN 0966-0429, E-ISSN 1365-2834, Vol. 17, nr 6, s. 718-729Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

     Aim The aim of the present study was to explore and describe what characterizes first-and second-line health care managers' use of time. Background Many Swedish health care managers experience difficulties managing their time. Methods Structured and unstructured observations were used. Ten first-and second-line managers in different health care settings were studied in detail from 3.5 and 4 days each. Duration and frequency of different types of work activities were analysed. Results The individual variation was considerable. The managers' days consisted to a large degree of short activities (<9 minutes). On average, nearly half of the managers' time was spent in meetings. Most of the managers' time was spent with subordinates and <1% was spent alone with their superiors. Sixteen per cent of their time was spent on administration and only a small fraction on explicit strategic work. Conclusions The individual variations in time use patterns suggest the possibility of interventions to support changes in time use patterns. Implications for nursing management A reliable description of what managers do paves the way for analyses of what they should do to be effective.

  • 162. Arman, Rebecka
    et al.
    Wikström, Ewa
    Tengelin, Ellinor
    Dellve, Lotta
    KTH, Skolan för teknik och hälsa (STH), Hälso- och systemvetenskap, Ergonomi.
    Work activities and stress among managers in health care2012Inngår i: The Work of Managers: Towards a Practice Theory of Management / [ed] Tengblad, Sten, Oxford: Oxford University Press, 2012, 1Kapittel i bok, del av antologi (Annet vitenskapelig)
    Abstract [en]

    This chapter reports on the work activities, time-use patterns, and stress patterns of ten health care managers in Sweden. The qualitative and quantitative evidence reveals the fragmentation in their nine-hour working days where each activity, on average, lasts only ten minutes. The time-use patterns vary individually though some patterns are related to position and unit type. Activities deal with the coexisting and competing logics of employeeship, administration, and strategy and risk handling. None of the managers’ approaches for handling the multiple legitimation processes and delimiting their workload boundaries really challenges the complexity of the coexistence of the multiple logics or the boundlessness of their working hours. Using biophysical measures, the research finds that stress reported by the managers is caused by (a) interruptions during challenging tasks and (b) personal situations such as private dilemmas and conflict-loaded or ineffective meetings. It is important to acknowledge managers’ fragmented working situation and to recognize that management should be seen as collective process, or as part of an administrative system.

  • 163. Arner, P.
    et al.
    Henjes, Frauke
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Schwenk, Jochen M.
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Darmanis, Spyros N.
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Dahlman, I.
    Iresjö, B. -M
    Naredi, P.
    Agustsson, T.
    Lundholm, K.
    Nilsson, Peter M.
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Rydén, M.
    Circulating Carnosine Dipeptidase 1 associates with weight loss and poor prognosis in gastrointestinal cancer2015Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, nr 4, artikkel-id e0123566Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Cancer cachexia (CC) is linked to poor prognosis. Although the mechanisms promoting this condition are not known, several circulating proteins have been proposed to contribute. We analyzed the plasma proteome in cancer subjects in order to identify factors associated with cachexia. Design/Subjects: Plasma was obtained from a screening cohort of 59 patients, newly diagnosed with suspected gastrointestinal cancer, with (n = 32) or without (n = 27) cachexia. Samples were subjected to proteomic profiling using 760 antibodies (targeting 698 individual proteins) from the Human Protein Atlas project. The main findings were validated in a cohort of 93 patients with verified and advanced pancreas cancer. Results: Only six proteins displayed differential plasma levels in the screening cohort. Among these, Carnosine Dipeptidase 1 (CNDP1) was confirmed by sandwich immunoassay to be lower in CC (p = 0.008). In both cohorts, low CNDP1 levels were associated with markers of poor prognosis including weight loss, malnutrition, lipid breakdown, low circulating albumin/IGF1 levels and poor quality of life. Eleven of the subjects in the discovery cohort were finally diagnosed with non-malignant disease but omitting these subjects from the analyses did not have any major influence on the results. Conclusions: In gastrointestinal cancer, reduced plasma levels of CNDP1 associate with signs of catabolism and poor outcome. These results, together with recently published data demonstrating lower circulating CNDP1 in subjects with glioblastoma and metastatic prostate cancer, suggest that CNDP1 may constitute a marker of aggressive cancer and CC.

  • 164.
    Aronsson, K
    et al.
    Karolinska Institutet.
    Teär Fahnehjelm, K
    Karolinska Institutet.
    Nylén, P
    KTH, Skolan för teknik och hälsa (STH), Ergonomi.
    Eklund, Jörgen
    KTH, Skolan för teknik och hälsa (STH), Ergonomi.
    Synergonomi och ögonbesvär hos personal på ögonsjukhus.2012Konferansepaper (Annet vitenskapelig)
    Abstract [sv]

    Ögonläkare, ögonsjuksköterskor, optiker och annan personal på ögonsjukhus arbetar ofta med synkrävande arbetsuppgifter i dämpad belysning eller helt utan allmänbelysning. Inför den planerade byggnationen av ett nytt ögonsjukhus i Stockholm ca år 2018 gjordes en enkätstudie för att kartlägga ögonbesvär och trötthet hos personalen på S:t Eriks Ögonsjukhus. Studien som är ett multidisciplinärt samarbetsprojekt mellan S:t Erik, Karolinska Institutet och Kungliga Tekniska Högskolan, syftar till att optimera belysning, dagsljusinsläpp och ljusmiljö vid det nya ögonsjukhuset.

    Totalt 265 anställda på S:t Eriks Ögonsjukhus samt 60 röntgenläkare och 45 barnläkare, varav de senare två  utgjorde jämförelsegrupper, inviterades till  studien.  Enkäten som distribuerades baserades på synergonomienkäter av Knave och Hemphälä och bestod av 31 validerade frågor om subjektiva ögonbesvär, nuvarande belysning, tillgång till dagsljus och välbefinnande. Ögonbesvären räknades om till ett gruppmedelvärde (ögonbesvärsindex) med avseende på svårighetsgrad och frekvens. Studien är godkänd av Etikprövningsnämnden. 

    Nittiosex av 265 (33%) anställda på S:t Eriks Ögonsjukhus hade t o m juni 2012 besvarat enkäten tillsammans med 23 röntgenläkare (38%) och 14 barnläkare (31%). Ögonbesvär som torrhets- och gruskänsla var vanligt förekommande hos alla yrkesgrupper på ögonsjukhuset och generellt vanligare hos kvinnor. Då samtliga grupper jämfördes med avseende på ögonbesvärsindex var skillnaden mellan män och kvinnor statistiskt säkerställd (p<0,05). Röntgenläkarna rapporterade högst ögonbesvärsindex och barnläkarna lägst, skillnaden mellan dessa yrkesgrupper var signifikant (p<0,05). Ögonpersonal och röntgenläkare som rapporterade att de ofta arbetade i mörker, associerade detta med  ökad trötthet i högre grad än  med barnläkarna (p<0,05).

    Ögonbesvär var vanliga hos ögonpersonalen inkluderade i studien. Den grupp som arbetade mest i mörker hade mer ögonbesvär än den grupp som arbetade minst i mörker. Kvinnor hade mer ögonbesvär än män. Arbete i mörker ökade den subjektiva känslan av trötthet . Optimala ljusförhållanden och bra synergonomi bör ges hög prioritet vid planering av ett nytt ögonsjukhus.

  • 165.
    Aronsson, K
    et al.
    Karolinska Institutet.
    Teär Fahnhjelm, K
    Karolinska Institutet.
    Nylén, P
    KTH, Skolan för teknik och hälsa (STH), Ergonomi.
    Eklund, Jörgen
    KTH, Skolan för teknik och hälsa (STH), Ergonomi.
    Visual ergonomics and eye strain in eye careprofessionals2012Inngår i: NES2012 Proceedings: Ergonomics for sustainability and growth / [ed] Ann-Beth Antonsson, Göran M Hägg, 2012Konferansepaper (Annet vitenskapelig)
    Abstract [en]

    Eye care professionals spend many hours a day in darkness performing visually demanding tasks. A new eye hospital will be built in Stockholm 2018. The current lighting, logistics, and working conditions are analysed in a multidisciplinary project aiming to optimise settings in the new hospital. The main purpose of the present project was to study visual ergonomics and current eye strain in employees at an eye hospital. Ninety-six employees answered a validated questionnaire regarding their experiences of light, visual ergonomics and eye strain problems. Twenty-three radiologists and 14 paediatricians at a university hospital were used as comparison groups. Eye strain was common in all departments at the hospital but was significantly more common only among radiologists compared to paediatricians. Overall, women experienced significantly more eye strain than men.

  • 166. Arruda, L. C. M.
    et al.
    Gaballa, A.
    Uhlin, Michael
    KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik, Biofysik. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Graft γδ TCR Sequencing Identifies Public Clonotypes Associated with Hematopoietic Stem Cell Transplantation Efficacy in Acute Myeloid Leukemia Patients and Unravels Cytomegalovirus Impact on Repertoire Distribution2019Inngår i: Journal of Immunology, ISSN 0022-1767, E-ISSN 1550-6606, Vol. 202, nr 6, s. 1859-1870Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Although the impact of donor graft composition on clinical outcomes after hematopoietic stem cell transplantation (HSCT) has been studied, little is known about the role of intragraft γδ TCR repertoire on clinical outcomes following HSCT. Using a high-throughput sequencing platform, we sought to analyze the TCR γ-chain (TRG) repertoire of γδ T cells within donor stem cell grafts and address its potential impact on clinical response in the corresponding patients. A total of 20 peripheral blood stem cell grafts were analyzed, and donors were classified as CMV+/- The respective acute myeloid leukemia recipients were followed for disease relapse and acute graft-versus-host disease (aGvHD) development post-HSCT. In all samples, TRG repertoire showed a reduced diversity and displayed overrepresented clones. This was more prominent in grafts from CMV+ donors, which presented a more private repertoire, lower diversity, skewed distribution, and reduced usage of the V9-JP pairing. Grafts given to nonrelapse patients presented a more public repertoire and increased presence of long sequence clonotypes. Variable-joining gene segment usage was not associated with aGvHD development, but a higher usage of V2-JP1 pairing and lower usage of V4-J2/V5-J2/V8-JP2 were observed in grafts given to nonrelapse patients. Our work identified five private overrepresented and one public CDR3 sequence (CATWDGPYYKKLF) associated with CMV infection, in addition to 12 highly frequent public sequences present exclusively in grafts given to nonrelapse patients. Our findings show that, despite CMV infection reshaping the TRG repertoire, TRG composition is not associated with aGvHD development, and several public sequences are associated with clinical remission.

  • 167.
    Arruda, Lucas C. M.
    et al.
    Karolinska Inst, CLINTEC, Stockholm, Sweden..
    Gaballa, Ahmed
    Karolinska Inst, CLINTEC, Stockholm, Sweden..
    Uhlin, Michael
    KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik, Biofysik. KTH, Centra, Science for Life Laboratory, SciLifeLab. Karolinska Inst, CLINTEC, Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm, Sweden..
    Graft gamma delta T-cell receptor sequencing identifies public clonotypes associated to HSCT efficacy in AML patients and unravels CMV impact on repertoire distribution2019Inngår i: Bone Marrow Transplantation, ISSN 0268-3369, E-ISSN 1476-5365, Vol. 54, s. 134-135Artikkel i tidsskrift (Annet vitenskapelig)
  • 168. Arvedsen, SK
    et al.
    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.
    Kölegård, Roger
    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.
    Petersen, L. G.
    Damgaard, M.
    Body height and arterial pressure in seated and supine young males during +2 G centrifugation2015Inngår i: American Journal of Physiology. Regulatory Integrative and Comparative Physiology, ISSN 0363-6119, E-ISSN 1522-1490, Vol. 309, nr 9Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    It is known that arterial pressure correlates positively with body height in males and it has been suggested that this is due to the increasing vertical hydrostatic gradient from the heart to the carotid baroreceptors. Therefore we tested the hypothesis that a higher gravitoinertial stress induced by the use of a human centrifuge would increase mean arterial pressure (MAP) more in tall than in short males in the seated position. In short (162-171cm, n=8) and tall (194-203cm, n=10) healthy males (18-41y), brachial arterial pressure, heart rate (HR) and cardiac output were measured during +2G centrifugation, while they were seated upright with the legs kept horizontal (+2Gz). In a separate experiment, the same measurements were done with the subjects supine (+2Gx). During +2Gz MAP increased in the short (22±2 mmHg, p<0.0001) and tall (23±2 mmHg, p<0.0001) males, with no significant difference between the groups. HR increased more (p<0.05) in the tall than in the short group (14±2 versus 7±2 bpm). Stroke volume (SV) decreased in the short group (26±4 mL, p=0.001) and more so in the tall group (39±5 mL, p<0.0001; short vs tall p=0.047). During +2GX, systolic arterial pressure increased (p<0.001) and SV (p=0.012) decreased in the tall group only. In conclusion, during +2Gz MAP increased in both short and tall males with no difference between the groups. However, in the tall group HR increased more during +2Gz which could be caused by a larger hydrostatic pressure gradient from heart to head leading to greater inhibition of the carotid baroreceptors.

  • 169.
    Arvidsson, M.
    et al.
    Karolinska Inst, Dept Lab Med, Stockholm, Sweden..
    Dahl, M. -L
    Beck, O.
    Karolinska Inst, Dept Lab Med, Stockholm, Sweden..
    Rosenborg, S.
    Karolinska Inst, Dept Lab Med, Stockholm, Sweden..
    Nordin, K.
    Karolinska Univ Hosp, Stockholm, Sweden..
    Lenk, Gabriel
    KTH, Skolan för elektroteknik och datavetenskap (EECS), Mikro- och nanosystemteknik.
    Pharmacokinetics of methylphenidate in plasma, exhaled breath, oral fluid and dried blood spots after a single oral dose of ritalin 20 mg2019Inngår i: European Journal of Clinical Pharmacology, ISSN 0031-6970, E-ISSN 1432-1041, Vol. 75, s. S89-S90Artikkel i tidsskrift (Annet vitenskapelig)
  • 170.
    Arvidsson, Martin
    et al.
    Department of Psychology, Stockholm University, Sweden.
    Berglund, Birgitta
    Department of Psychology, Stockholm University, Sweden.
    Skedung, Lisa
    KTH, Skolan för kemivetenskap (CHE), Kemi.
    Aikala, Maiju
    Oy Keskuslaboratorio - Centrallaboratorium Ab (KCL), Espoo, Finland.
    Danerlöv, Katrin
    Institute for Surface Chemistry (YTK), Stockholm, Sweden.
    Kettle, John
    Oy Keskuslaboratorio - Centrallaboratorium Ab (KCL), Espoo, Finland.
    Rutland, Mark W.
    KTH, Skolan för kemivetenskap (CHE), Kemi, Ytkemi.
    Multidimensional psychophysics: surface feel of printing paper as a function of physical propertiesManuskript (preprint) (Annet vitenskapelig)
  • 171.
    Asem, Heba
    et al.
    KTH, Skolan för informations- och kommunikationsteknik (ICT), Material- och nanofysik, Funktionella material, FNM. Karolinska Inst, Sweden.
    Abd El-Fattah, Ahmed
    Nafee, Noha
    Zhao, Ying
    Khalil, Labiba
    Muhammed, Mamoun
    KTH, Skolan för informations- och kommunikationsteknik (ICT), Material- och nanofysik, Funktionella material, FNM.
    Hassan, Moustapha
    Kandil, Sherif
    Development and biodistribution of a theranostic aluminum phthalocyanine nanophotosensitizer2016Inngår i: Photodiagnosis and Photodynamic Therapy, ISSN 1572-1000, E-ISSN 1873-1597, Vol. 13, s. 48-57Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Aluminum phthalocyanine (AlPc) is an efficient second generation photosensitizer (PS) with high fluorescence ability. Its use in photodynamic therapy (PDT) is hampered by hydrophobicity and poor biodistribution. Methods: AlPc was converted to a biocompatible nanostructure by incorporation into amphiphilic polyethylene glycol-polycaprolactone (PECL) copolymer nanoparticles, allowing efficient entrapment of the PS in the hydrophobic core, water dispersibility and biodistribution enhancement by PEG-induced surface characteristics. A series of synthesized PECL copolymers were used to prepare nanophotosensitizers with an average diameter of 66.5-99.1 nm and encapsulation efficiency (EE%) of 66.4-78.0%. One formulation with favorable colloidal properties and relatively slow release over 7 days was selected for in vitro photophysical assessment and in vivo biodistribution studies in mice. Results: The photophysical properties of AlPc were improved by encapsulating AlPc into PECL-NPs, which showed intense fluorescence emission at 687 nm and no AlPc aggregation has been induced after entrapment into the nanoparticles. Biodistribution of AlPc loaded NPs (AlPc-NPs) and free AlPc drug in mice was monitored by in vivo whole body fluorescence imaging and ex vivo organ imaging, with in vivo imaging system (IVIS). Compared to a AlPc solution in aqueous TWEEN 80 (2 w/v%), the developed nanophotosensitizer showed targeted drug delivery to lungs, liver and spleen as monitored by the intrinsic fluorescence of AlPc at different time points (1 h, 24 h and 48 h) post iv. administration. Conclusions: The AlPc-based copolymer nanoparticles developed offer potential as a single agent multifunctional theranostic nanophotosensitizer for PDT coupled with imaging-guided drug delivery and biodistribution, and possibly also fluorescence diagnostics.

  • 172. Ashokkumar, M.
    et al.
    Aralaguppe, S. G.
    Tripathy, S. P.
    Hanna, L. E.
    Neogi, Ujjwal
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab. Karolinska Inst, Dept Lab Med, Stockholm, Sweden.
    Unique phenotypic characteristics of recently transmitted HIV-1 subtype C envelope glycoprotein gp120: Use of CXCR6 coreceptor by transmitted founder viruses2018Inngår i: Journal of Virology, ISSN 0022-538X, E-ISSN 1098-5514, Vol. 92, nr 9, artikkel-id e00063-18Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Adequate information on the precise molecular and biological composition of the viral strains that establish HIV infection in the human host will provide effective means of immunization against HIV infection. In an attempt to identify the transmitted founder (TF) virus and differentiate the biological properties and infectious potential of the TF virus from those of the population of the early transmitted viruses, 250 patient-derived gp120 envelope glycoproteins were cloned in pMN-K7- Luc-IRESs-NefΔgp120 to obtain chimeric viruses. Samples were obtained from eight infants who had recently become infected with HIV through mother-to-child transmission (MTCT) and two adults who acquired infection through the heterosexual route and were in the chronic stage of infection. Among the 250 clones tested, 65 chimeric viruses were infectious, and all belonged to HIV-1 subtype C. The 65 clones were analyzed for molecular features of the envelope, per-infectious-particle infectivity, coreceptor tropism, drug sensitivity, and sensitivity to broadly neutralizing antibodies. Based on genotypic and phenotypic analysis of the viral clones, we identified 10 TF viruses from the eight infants. The TF viruses were characterized by shorter V1V2 regions, a reduced number of potential N-linked glycosylation sites, and a higher infectivity titer compared to the virus variants from the adults in the chronic stage of infection. CXCR6 coreceptor usage, in addition to that of the CCR5 coreceptor, which was used by all 65 chimeric viruses, was identified in 13 viruses. The sensitivity of the TF variants to maraviroc and a standard panel of neutralizing monoclonal antibodies (VRC01, PG09, PG16, and PGT121) was found to be much lower than that of the virus variants from the adults in the chronic stage of infection.

  • 173.
    Asiimwe, Savina
    et al.
    Makerere Univ, Sch Biosci, Kampala, Uganda.
    Kamatenesi-Mugisha, Maud
    Namutebi, Agnes
    Borg-Karlsson, Anna-Karin
    KTH, Skolan för kemivetenskap (CHE), Kemi, Organisk kemi.
    Musiimenta, Peace
    Ethnobotanical study of nutri-medicinal plants used for the management of HIV/AIDS opportunistic ailments among the local communities of western Uganda2013Inngår i: Journal of Ethnopharmacology, ISSN 0378-8741, E-ISSN 1872-7573, Vol. 150, nr 2, s. 639-648Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Ethnopharmacological relevance: Herbal remedies are a source of therapeutics for nearly 80% of the population in Uganda. Poor health facilities and limited access to antiretroviral drugs have perpetuated and increased the use of traditional medicine especially in rural areas for the treatment of opportunistic ailments of HIV/AIDS. To document the traditional uses of nutri-medicinal plants in the management of immunocompromised ailments associated with HIV/AIDS. To document the parts and growth forms of plants used, methods of preparation and administration of the herbal remedies. Materials and methods: The study was conducted in Mbarara and Isingiro districts of western Uganda between December 2010 and May 2011. Ethnobotanical information was collected from 64 respondents who were sampled based on recommendations of local elders and administrators. Ethnobotanical data on the use of nutri-medicinal plants for traditional treatment of HIV/AIDS opportunistic ailments were collected by employing semi-structured interviews with selected respondents, house hold visits and field observations as described by (Martin, 1995a). The respondents were mainly traditional medical practitioners who treat patients who are already receiving antiretroviral drugs. Fidelity levels of plant species and informant consensus factor were determined to show the percentage of informants claiming the use of certain plant species for the same major purpose and to analyse people's knowledge of plant use. Results: The study revealed 81 plant species most of which were herbs (49%). Leaves (71%) were the most frequently used parts in remedy preparations which were mainly administered orally (85%). The majority of plants (54%) were harvested from wild populations. Hibiscus sabdariffa L, Plumeria obtusa L, and Abutilon guineense (Shumach.) Baker. F and Exell were the nutri-medicinal plants that scored the highest Fidelity level values. The informant's consensus about usages of plants ranged from 0.75 to 0.80. Plants that are presumed to be effective in treating a certain disease have higher informant consensus factor (ICF) values. Family Asteraceae accounted for 18% of the total species recorded. Thirteen species (16%) of the plants are edible and provide nutritional support. Conclusion: The study recorded plant species with potential to treat ailments associated with immunocompromised people living with HIV/AIDS in western Uganda. Such studies can help stimulate confidence in traditional medicine and enhance appreciation of herbal medicine among the people and to appreciate the value of the plant resources and therefore enhance conservation efforts of the plant species. The high consensus means the majority of informants agree on the use of plant species and this reflects the intercultural relevance and the agreement in the use of the nutri-medicinal plants to the people. We recommend the documented plants for further Ethnopharmacological studies.

  • 174.
    Asp, Michaela
    et al.
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Giacomello, Stefania
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Larsson, Ludvig
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Wu, Chenglin
    Stockholm Univ, Dept Biochem & Biophys, Sci Life Lab, Stockholm, Sweden..
    Furth, Daniel
    Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA..
    Qian, Xiaoyan
    Stockholm Univ, Dept Biochem & Biophys, Sci Life Lab, Stockholm, Sweden..
    Wardell, Eva
    Karolinska Inst, Dept Med, Huddinge, Sweden..
    Custodio, Joaquin
    Karolinska Inst, Dept Med Biochem & Biophys, Sci Life Lab, Stockholm, Sweden..
    Reimegard, Johan
    Uppsala Univ, Dept Cell & Mol Biol, Sci Life Lab, Natl Bioinformat Infrastruct Sweden, Uppsala, Sweden..
    Salmen, Fredrik
    Royal Netherlands Acad Arts & Sci, Hubrecht Inst KNAW, Utrecht, Netherlands.;Univ Med Ctr Utrecht, Canc Genom Netherlands, Utrecht, Netherlands..
    Österholm, Cecilia
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden..
    Ståhl, Patrik
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi.
    Sundström, Erik
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, R&D Unit, Stockholms Sjukhem, Stockholm, Sweden..
    Åkesson, Elisabet
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, R&D Unit, Stockholms Sjukhem, Stockholm, Sweden..
    Bergmann, Olaf
    Tech Univ Dresden, Ctr Regenerat Therapies Dresden, Dresden, Germany.;Karolinska Inst, Cell & Mol Biol, Stockholm, Sweden..
    Bienko, Magda
    Karolinska Inst, Dept Med Biochem & Biophys, Sci Life Lab, Stockholm, Sweden..
    Mansson-Broberg, Agneta
    Karolinska Inst, Dept Med, Huddinge, Sweden..
    Nilsson, Mats
    Stockholm Univ, Dept Biochem & Biophys, Sci Life Lab, Stockholm, Sweden..
    Sylven, Christer
    Karolinska Inst, Dept Med, Huddinge, Sweden..
    Lundeberg, Joakim
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi.
    A Spatiotemporal Organ-Wide Gene Expression and Cell Atlas of the Developing Human Heart2019Inngår i: Cell, ISSN 0092-8674, E-ISSN 1097-4172, Vol. 179, nr 7, s. 1647-+Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The process of cardiac morphogenesis in humans is incompletely understood. Its full characterization requires a deep exploration of the organ-wide orchestration of gene expression with a single-cell spatial resolution. Here, we present a molecular approach that reveals the comprehensive transcriptional landscape of cell types populating the embryonic heart at three developmental stages and that maps cell-type-specific gene expression to specific anatomical domains. Spatial transcriptomics identified unique gene profiles that correspond to distinct anatomical regions in each developmental stage. Human embryonic cardiac cell types identified by single-cell RNA sequencing confirmed and enriched the spatial annotation of embryonic cardiac gene expression. In situ sequencing was then used to refine these results and create a spatial subcellular map for the three developmental phases. Finally, we generated a publicly available web resource of the human developing heart to facilitate future studies on human cardiogenesis.

  • 175.
    Asplund, Maria
    KTH, Skolan för teknik och hälsa (STH), Neuronik.
    Conjugated Polymers for Neural Interfaces: Prospects, possibilities and future challenges2009Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Within the field of neuroprosthetics the possibility to use implanted electrodes for communication with the nervous system is explored. Much effort is put into the material aspects of the electrode implant to increase charge injection capacity, suppress foreign body response and build micro sized electrode arrays allowing close contact with neurons. Conducting polymers, in particular poly(3,4-ethylene dioxythiophene) (PEDOT), have been suggested as materials highly interesting for such neural communication electrodes. The possibility to tailor the material both mechanically and biochemically to suit specific applications, is a substantial benefit with polymers when compared to metals. PEDOT also have hybrid charge transfer properties, including both electronic and ionic conduction, which allow for highly efficient charge injection.

     

    Part of this thesis describes a method of tailoring PEDOT through exchanging the counter ion used in electropolymerisation process. Commonly used surfactants can thereby be excluded and instead, different biomolecules can be incorporated into the polymer. The electrochemical characteristics of the polymer film depend on the ion. PEDOT electropolymerised with heparin was here determined to have the most advantageous properties. In vitro methods were applied to confirm non-cytotoxicity of the formed PEDOT:biomolecular composites. In addition, biocompatibility was affirmed for PEDOT:heparin by evaluation of inflammatory response and neuron density when implanted in rodent cortex.

     

    One advantage with PEDOT often stated, is its high stability compared to other conducting polymers. A battery of tests simulating the biological environment was therefore applied to investigate this stability, and especially the influence of the incorporated heparin. These tests showed that there was a decline in the electroactivity of PEDOT over time. This also applied in phosphate buffered saline at body temperature and in the absence of other stressors. The time course of degradation also differed depending on whether the counter ion was the surfactant polystyrene sulphonate or heparin, with a slightly better stability for the former.

     

    One possibility with PEDOT, often overlooked for biological applications, is the use of its semi conducting properties in order to include logic functions in the implant. This thesis presents the concept of using PEDOT electrochemical transistors to construct textile electrode arrays with in-built multiplexing. Using the electrolyte mediated interaction between adjacent PEDOT coated fibres to switch the polymer coat between conducting and non conducting states, then transistor function can be included in the conducting textile. Analogue circuit simulations based on experimentally found transistor characteristics proved the feasibility of these textile arrays. Developments of better polymer coatings, electrolytes and encapsulation techniques for this technology, were also identified to be essential steps in order to make these devices truly useful.

     

    In summary, this work shows the potential of PEDOT to improve neural interfaces in several ways. Some weaknesses of the polymer and the polymer electronics are presented and this, together with the epidemiological data, should point in the direction for future studies within this field.

  • 176.
    Asplund, Maria
    et al.
    KTH, Skolan för teknik och hälsa (STH), Neuronik.
    Nilsson, Mats
    KTH, Skolan för teknik och hälsa (STH), Neuronik.
    Jacobsson, Anders
    von Holst, Hans
    KTH, Skolan för teknik och hälsa (STH), Neuronik.
    Incidence of traumatic peripheral nerve injuries and amputations in Sweden between 1998 and 20062008Inngår i: Neuroepidemiology, ISSN 0251-5350, E-ISSN 1423-0208Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: To define the epidemiological pattern of nerve injuries and traumatic amputations in Sweden, 1998-2006, and investigate possible targets for emerging neural engineering and neuroprosthetic technologies.

    Methods: The Swedish Hospital Discharge Register was used as basis of information, including data from all public in-patient care, excluding out-patient data. ICD-10 codes were screened for nerve injuries and traumatic amputations of high incidence or in-patient care time. Selected codes, causing factors, age and gender distribution were discussed in detail, and potential targets for tailored solutions were identified.

    Results: Incidence rate was determined to 13.9 for nerve injuries and 5.21 for amputations per 100 000 person-yrs. The majority of injuries occurred at wrist and hand level although it could be concluded that these are often minor injuries requiring less than a week of hospitalization. The single most care consuming nerve injury was brachial plexus injury constituting, in average, 68 injuries and 960 hospital days annually. When minor amputations of fingers and toes were disregarded, most frequent site of amputation was between knee and ankle (24 patients / year).

    Conclusions: Based on analysis of incidence and care time, we find that brachial plexus injuries and lower leg amputations should be primary targets of these new technologies.

  • 177.
    Astaraki, Mehdi
    et al.
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Medicinteknik och hälsosystem, Medicinsk avbildning.
    Wang, Chunliang
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Medicinteknik och hälsosystem, Medicinsk avbildning.
    Buizza, G.
    Toma-Dasu, I.
    Lazzeroni, M.
    Smedby, Örjan
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Medicinteknik och hälsosystem, Medicinsk avbildning.
    Early survival prediction in non-small cell lung cancer with PET/CT size aware longitudinal pattern2019Inngår i: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, ISSN 0167-8140, Vol. 133, s. S208-S209Artikkel i tidsskrift (Fagfellevurdert)
  • 178.
    Astaraki, Mehdi
    et al.
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Medicinteknik och hälsosystem, Medicinsk avbildning. Karolinska Inst, Dept Oncol Pathol, Karolinska Univ Sjukhuset, SE-17176 Stockholm, Sweden.
    Wang, Chunliang
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Medicinteknik och hälsosystem, Medicinsk avbildning.
    Buizza, Giulia
    Politecn Milan, Dept Elect Informat & Bioengn, Piazza Leonardo da Vinci 42, I-20133 Milan, Italy..
    Toma-Dasu, Iuliana
    Karolinska Inst, Dept Oncol Pathol, Karolinska Univ Sjukhuset, SE-17176 Stockholm, Sweden.;Stockholm Univ, Dept Phys, SE-10691 Stockholm, Sweden..
    Lazzeroni, Marta
    Karolinska Inst, Dept Oncol Pathol, Karolinska Univ Sjukhuset, SE-17176 Stockholm, Sweden.;Stockholm Univ, Dept Phys, SE-10691 Stockholm, Sweden..
    Smedby, Örjan
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Medicinteknik och hälsosystem, Medicinsk avbildning.
    Early survival prediction in non-small cell lung cancer from PET/CT images using an intra-tumor partitioning method2019Inngår i: Physica medica (Testo stampato), ISSN 1120-1797, E-ISSN 1724-191X, Vol. 60, s. 58-65Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose: To explore prognostic and predictive values of a novel quantitative feature set describing intra-tumor heterogeneity in patients with lung cancer treated with concurrent and sequential chemoradiotherapy. Methods: Longitudinal PET-CT images of 30 patients with non-small cell lung cancer were analysed. To describe tumor cell heterogeneity, the tumors were partitioned into one to ten concentric regions depending on their sizes, and, for each region, the change in average intensity between the two scans was calculated for PET and CT images separately to form the proposed feature set. To validate the prognostic value of the proposed method, radiomics analysis was performed and a combination of the proposed novel feature set and the classic radiomic features was evaluated. A feature selection algorithm was utilized to identify the optimal features, and a linear support vector machine was trained for the task of overall survival prediction in terms of area under the receiver operating characteristic curve (AUROC). Results: The proposed novel feature set was found to be prognostic and even outperformed the radiomics approach with a significant difference (AUROC(sALop) = 0.90 vs. AUROC(radiomic) = 0.71) when feature selection was not employed, whereas with feature selection, a combination of the novel feature set and radiomics led to the highest prognostic values. Conclusion: A novel feature set designed for capturing intra-tumor heterogeneity was introduced. Judging by their prognostic power, the proposed features have a promising potential for early survival prediction.

  • 179.
    Atefi, Seyed Reza
    et al.
    KTH, Skolan för teknik och hälsa (STH), Medicinska sensorer, signaler och system (MSSS).
    Seoane, Fernando
    KTH, Skolan för teknik och hälsa (STH), Medicinska sensorer, signaler och system (MSSS).
    Lindecrantz, Kaj
    KTH, Skolan för teknik och hälsa (STH), Medicinska sensorer, signaler och system (MSSS).
    Electrical Bioimpedance cerebral monitoring. Preliminary results from measurements on stroke patients2012Inngår i: Engineering in Medicine and Biology Society (EMBC), 2012 Annual International Conference of the IEEE, IEEE , 2012, s. 126-129Konferansepaper (Fagfellevurdert)
    Abstract [en]

    Electrical Bioimpedance Spectroscopy (EBIS) is currently used in different tissue characterization applications. In this work we aim to use EBIS to study changes in electrical properties of the cerebral tissues after an incident of hemorrhage/ischemic stroke. To do so a case-control study was conducted using six controls and three stroke cases. The preliminary results of this study show that by using Cole-based analysis on EBIS measurements and analyzing the Cole parameters R0 and R∞, it is possible to detect changes on electrical properties of cerebral tissue after stroke. 

  • 180. Auer, M.
    et al.
    Stollberger, R.
    Regitnig, P.
    Ebner, F.
    Holzapfel, Gerhard A.
    KTH, Skolan för teknikvetenskap (SCI), Hållfasthetslära (Inst.), Biomekanik.
    In Vitro Angioplasty of Atherosclerotic Human Femoral Arteries: Analysis of the Geometrical Changes in the Individual Tissues Using MRI and Image Processing2010Inngår i: Annals of Biomedical Engineering, ISSN 0090-6964, E-ISSN 1573-9686, Vol. 38, nr 4, s. 1276-1287Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Existing atherosclerotic plaque imaging techniques such as intravascular ultrasound, multidetector computed tomography, optical coherence tomography, and high-resolution magnetic resonance imaging (hrMRI) require computerized methods to separate and analyze the plaque morphology. In this work, we perform in vitro balloon angioplasty experiments with 10 human femoral arteries using hrMRI and image processing. The vessel segments contain low-grade to high-grade lesions with very different plaque compositions. The experiments are designed to mimic the in vivo situation. We use a semi-automatic image processing tool to extract the three-dimensional (3D) geometries of the tissue components at four characteristic stages of the angioplasty procedure. The obtained geometries are then used to determine geometrical and mechanical indices in order to characterize, classify, and analyze the atherosclerotic plaques by their specific geometrical changes. During inflation, three vessels ruptured via helical crack propagation. The adventitia, media, and intima did not preserve their area/volume during inflation; the area changes of the lipid pool during inflation were significant. The characterization of changes in individual 3D tissue geometries, together with tissue-specific mechanical properties, may serve as a basis for refined finite element (FE) modeling, which is key to better understand stress evolution in various atherosclerotic plaque configurations.

  • 181.
    Auffarth, Benjamin
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Understanding smell: the olfactory stimulus problem2013Inngår i: Neuroscience and Biobehavioral Reviews, ISSN 0149-7634, E-ISSN 1873-7528, Vol. 37, nr 8, s. 1667-1679Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    The main problem with sensory processing is the difficulty in relating sensory input to physiological responses and perception. This is especially problematic at higher levels of processing, where complex cues elicit highly specific responses. In olfaction, this relationship is particularly obfuscated by the difficulty of characterizing stimulus statistics and perception. The core questions in olfaction are hence the so-called stimulus problem, which refers to the understanding of the stimulus, and the structure–activity and structure–odor relationships, which refer to the molecular basis of smell. It is widely accepted that the recognition of odorants by receptors is governed by the detection of physico-chemical properties and that the physical space is highly complex. Not surprisingly, ideas differ about how odor stimuli should be classified and about the very nature of information that the brain extracts from odors. Even though there are many measures for smell, there is none that accurately describes all aspects of it. Here, we summarize recent developments in the understanding of olfaction. We argue that an approach to olfactory function where information processing is emphasized could contribute to a high degree to our understanding of smell as a perceptual phenomenon emerging from neural computations. Further, we argue that combined analysis of the stimulus, biology, physiology, and behavior and perception can provide new insights into olfactory function. We hope that the reader can use this review as a competent guide and overview of research activities in olfactory physiology, psychophysics, computation, and psychology. We propose avenues for research, particularly in the systematic characterization of receptive fields and of perception.

  • 182.
    Auffarth, Benjamin
    et al.
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Kaplan, Bernhard
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Anders, Lansner
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Map formation in the olfactory bulb by axon guidance of olfactory neurons2011Inngår i: Frontiers in Systems Neuroscience, ISSN 1662-5137, E-ISSN 1662-5137, Vol. 5, nr 0Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The organization of representations in the brain has been observed to locally reflect subspaces of inputs that are relevant to behavioral or perceptual feature combinations, such as in areas receptive to lower and higher-order features in the visual system. The early olfactory system developed highly plastic mechanisms and convergent evidence indicates that projections from primary neurons converge onto the glomerular level of the olfactory bulb (OB) to form a code composed of continuous spatial zones that are differentially active for particular physico?-chemical feature combinations, some of which are known to trigger behavioral responses. In a model study of the early human olfactory system, we derive a glomerular organization based on a set of real-world,biologically-relevant stimuli, a distribution of receptors that respond each to a set of odorants of similar ranges of molecular properties, and a mechanism of axon guidance based on activity. Apart from demonstrating activity-dependent glomeruli formation and reproducing the relationship of glomerular recruitment with concentration, it is shown that glomerular responses reflect similarities of human odor category perceptions and that further, a spatial code provides a better correlation than a distributed population code. These results are consistent with evidence of functional compartmentalization in the OB and could suggest a function for the bulb in encoding of perceptual dimensions.

  • 183. Awasthi, Saurabh
    et al.
    Murugan, N. Arul
    KTH, Skolan för bioteknologi (BIO), Teoretisk kemi och biologi.
    Saraswathi, N. T.
    Advanced Glycation End Products Modulate Structure and Drug Binding Properties of Albumin2015Inngår i: Molecular Pharmaceutics, ISSN 1543-8384, E-ISSN 1543-8392, Vol. 12, nr 9, s. 3312-3322Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The extraordinary ligand binding properties of albumin makes it a key player in the pharmacokinetics and pharmacodynamics of many vital drugs. Albumin is highly susceptible for nonenzymatic glycation mediated structural modifications, and there is a need to determine structural and functional impact of specific AGEs modifications. The present study was aimed toward determining the AGE mediated structure and function changes, primarily looking into the effect on binding affinity of drugs in the two major drug binding sites of albumin. The impact of the two most predominant AGEs modifications, i.e., carboxyethyllysine (CEL) and argpyrimidine (Arg-P), was studied on the basis of the combination of in vitro and in silico experiments. In vitro studies were carried out by AGEs modification of bovine serum albumin (BSA) for the formation of Arg-P and CEL followed by drug interaction studies. In silico studies involved molecular dynamics (MD) simulations and docking studies for native and AGEs modified BSAs. In particular the side chain modification was specifically carried out for the residues in the drug binding sites, i.e., Arg-194, Arg-196, Arg-198, and Arg-217, and Lys-204 (site I) and Arg-409 and Lys-413 (site II). The equilibrated structures of native BSA (n-BSA) and glycated BSA (G-BSA) as obtained from MD were used for drug binding studies using molecular docking approach. It was evident from the results of both in vitro and in silico drug interaction studies that AGEs modification results in the reduced drug binding affinity for tolbutamide (TLB) and ibuprofen (IBP) in sites I and II. Moreover, the AGEs modification mediated conformational changes resulted in the shallow binding pockets with reduced accessibility for drugs.

  • 184. Aydoğdu, Eylem
    et al.
    Katchy, Anne
    Tsouko, Efrosini
    Lin, Chin-Yo
    Haldosén, Lars-Arne
    Helguero, Luisa
    Williams, Cecilia
    University of Houston.
    MicroRNA-regulated gene networks during mammary cell differentiation are associated with breast cancer.2012Inngår i: Carcinogenesis, ISSN 0143-3334, E-ISSN 1460-2180, Vol. 33, nr 8, s. 1502-11Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    MicroRNAs (miRNAs) play pivotal roles in stem cell biology, differentiation and oncogenesis and are of high interest as potential breast cancer therapeutics. However, their expression and function during normal mammary differentiation and in breast cancer remain to be elucidated. In order to identify which miRNAs are involved in mammary differentiation, we thoroughly investigated miRNA expression during functional differentiation of undifferentiated, stem cell-like, murine mammary cells using two different large-scale approaches followed by qPCR. Significant changes in expression of 21 miRNAs were observed in repeated rounds of mammary cell differentiation. The majority, including the miR-200 family and known tumor suppressor miRNAs, was upregulated during differentiation. Only four miRNAs, including oncomiR miR-17, were downregulated. Pathway analysis indicated complex interactions between regulated miRNA clusters and major pathways involved in differentiation, proliferation and stem cell maintenance. Comparisons with human breast cancer tumors showed the gene profile from the undifferentiated, stem-like stage clustered with that of poor-prognosis breast cancer. A common nominator in these groups was the E2F pathway, which was overrepresented among genes targeted by the differentiation-induced miRNAs. A subset of miRNAs could further discriminate between human non-cancer and breast cancer cell lines, and miR-200a/miR-200b, miR-146b and miR-148a were specifically downregulated in triple-negative breast cancer cells. We show that miR-200a/miR-200b can inhibit epithelial-mesenchymal transition (EMT)-characteristic morphological changes in undifferentiated, non-tumorigenic mammary cells. Our studies propose EphA2 as a novel and important target gene for miR-200a. In conclusion, we present evidentiary data on how miRNAs are involved in mammary cell differentiation and indicate their related roles in breast cancer.

  • 185.
    Ayoglu, Burcu
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Affinity Arrays for Profiling Proteins and Autoantibody Repertoires2014Doktoravhandling, med artikler (Annet vitenskapelig)
  • 186.
    Ayoglu, Burcu
    et al.
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Chaouch, Amina
    Lochmüller, Hanns
    Politano, Luisa
    Bertini, Enrico
    Spitali, Pietro
    Hiller, Monika
    Niks, Eric H.
    Gualandi, Francesca
    Pontén, Fredrik
    Bushby, Kate
    Aartsma-Rus, Annemieke
    Schwartz, Elena
    Le Priol, Yannick
    Straub, Volker
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Cirak, Sebahattin
    't Hoen, Peter A. C.
    Muntoni, Francesco
    Ferlini, Alessandra
    Schwenk, Jochen M.
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Nilsson, Peter
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Szigyarto, Cristina Al-Khalili
    Affinity proteomics within rare diseases: a BIO-NMD study for blood biomarkers of muscular dystrophies2014Inngår i: EMBO Molecular Medicine, ISSN 1757-4676, E-ISSN 1757-4684, Vol. 6, nr 7, s. 918-936Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Despite the recent progress in the broad-scaled analysis of proteins in body fluids, there is still a lack in protein profiling approaches for biomarkers of rare diseases. Scarcity of samples is the main obstacle hindering attempts to apply discovery driven protein profiling in rare diseases. We addressed this challenge by combining samples collected within the BIO-NMD consortium from four geographically dispersed clinical sites to identify protein markers associated with muscular dystrophy using an antibody bead array platform with 384 antibodies. Based on concordance in statistical significance and confirmatory results obtained from analysis of both serum and plasma, we identified eleven proteins associated with muscular dystrophy, among which four proteins were elevated in blood from muscular dystrophy patients: carbonic anhydrase III (CA3) and myosin light chain 3 (MYL3), both specifically expressed in slow-twitch muscle fibers and mitochondrial malate dehydrogenase 2 (MDH2) and electron transfer flavo-protein A (ETFA). Using age-matched sub-cohorts, 9 protein profiles correlating with disease progression and severity were identified, which hold promise for the development of new clinical tools for management of dystrophinopathies.

  • 187.
    Ayoglu, Burcu
    et al.
    KTH, Skolan för bioteknologi (BIO), Proteomik (stängd 20130101).
    Häggmark, Anna
    KTH, Skolan för bioteknologi (BIO), Proteomik (stängd 20130101).
    Neiman, Maja
    KTH, Skolan för bioteknologi (BIO), Proteomik (stängd 20130101).
    Igel, Ulrika
    KTH, Skolan för bioteknologi (BIO), Proteomik (stängd 20130101).
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO), Proteomik (stängd 20130101).
    Schwenk, Jochen
    KTH, Skolan för bioteknologi (BIO), Proteomik (stängd 20130101).
    Nilsson, Peter
    KTH, Skolan för bioteknologi (BIO), Proteomik (stängd 20130101).
    Systematic antibody and antigen-based proteomic profiling with microarrays2011Inngår i: EXPERT REVIEW OF MOLECULAR DIAGNOSTICS, ISSN 1473-7159, Vol. 11, nr 2, s. 219-234Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Current approaches within affinity-based proteomics are driven both by the accessibility and availability of antigens and capture reagents, and by suitable multiplexed technologies onto which these are implemented. By combining planar microarrays and other multiparallel systems with sets of reagents, possibilities to discover new and unpredicted protein disease associations, either via directed hypothesis-driven or via undirected hypothesis-generating target selection, can be created. In the following stages, the discoveries made during these screening phases have to be verified for potential clinical relevance based on both technical and biological aspects. The use of affinity tools throughout discovery and verification has the potential to streamline the introduction of new markers, as transition into clinically required assay formats appears straightforward. In this article, we summarize some of the current building blocks within array-and affinity-based proteomic profiling with a focus on body fluids, by giving a perspective on how current and upcoming developments in this bioscience could enable a path of pursuit for biomarker discovery.

  • 188.
    Ayoglu, Burcu
    et al.
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Kockum, Ingrid
    Olsson, Tomas
    Nilsson, Peter
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Anoctamin 2 identified as an autoimmune target in multiple sclerosis2016Inngår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 22, s. 10-10Artikkel i tidsskrift (Annet vitenskapelig)
  • 189.
    Ayoglu, Burcu
    et al.
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Mitsios, N.
    Khademi, M.
    Alfredsson, L.
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Mulder, J.
    Olsson, T.
    Schwenk, Jochen
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Nilsson, Peter
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Anoctamin 2, a novel autoimmune target candidate in multiple sclerosis2014Inngår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 20, s. 49-50Artikkel i tidsskrift (Annet vitenskapelig)
  • 190.
    Ayoglu, Burcu
    et al.
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Mitsios, Nicholas
    Kockum, Ingrid
    Khademi, Mohsen
    Zandian, Arash
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Sjoberg, Ronald
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Forsstrom, Bjorn
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Bredenberg, Johan
    Bomfim, Izaura Lima
    Holmgren, Erik
    Gronlund, Hans
    Guerreiro-Cacais, Andre Ortlieb
    Abdelmagid, Nada
    Uhlen, Mathias
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Waterboer, Tim
    Alfredsson, Lars
    Mulder, Jan
    Schwenk, Jochen M.
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Olsson, Tomas
    Nilsson, Peter
    Anoctamin 2 identified as an autoimmune target in multiple sclerosis2016Inngår i: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 113, nr 8, s. 2188-2193Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Multiple sclerosis (MS) is the most common chronic inflammatory disease of the central nervous system and also is regarded as an autoimmune condition. However, the antigenic targets of the autoimmune response in MS have not yet been deciphered. In an effort to mine the autoantibody repertoire within MS, we profiled 2,169 plasma samples from MS cases and population-based controls using bead arrays built with 384 human protein fragments selected from an initial screening with 11,520 antigens. Our data revealed prominently increased autoantibody reactivity against the chloride-channel protein anoctamin 2 (ANO2) in MS cases compared with controls. This finding was corroborated in independent assays with alternative protein constructs and by epitope mapping with peptides covering the identified region of ANO2. Additionally, we found a strong interaction between the presence of ANO2 autoantibodies and the HLA complex MS-associated DRB1*15 allele, reinforcing a potential role for ANO2 autoreactivity in MS etiopathogenesis. Furthermore, immunofluorescence analysis in human MS brain tissue showed ANO2 expression as small cellular aggregates near and inside MS lesions. Thus this study represents one of the largest efforts to characterize the autoantibody repertoire within MS. The findings presented here demonstrate that an ANO2 autoimmune subphenotype may exist in MS and lay the groundwork for further studies focusing on the pathogenic role of ANO2 autoantibodies in MS.

  • 191. Azimi, A.
    et al.
    Caramuta, S.
    Seashore-Ludlow, B.
    Boström, J.
    Robinson, J. L.
    Edfors, Fredrik
    KTH, Skolan för bioteknologi (BIO). KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Tuominen, R.
    Kemper, K.
    Krijgsman, O.
    Peeper, D. S.
    Nielsen, J.
    Hansson, J.
    Egyhazi Brage, S.
    Altun, M.
    Uhlén, Mathias
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för bioteknologi (BIO).
    Maddalo, G.
    Targeting CDK2 overcomes melanoma resistance against BRAF and Hsp90 inhibitors2018Inngår i: Molecular Systems Biology, ISSN 1744-4292, E-ISSN 1744-4292, Vol. 14, nr 3, artikkel-id e7858Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Novel therapies are undergoing clinical trials, for example, the Hsp90 inhibitor, XL888, in combination with BRAF inhibitors for the treatment of therapy-resistant melanomas. Unfortunately, our data show that this combination elicits a heterogeneous response in a panel of melanoma cell lines including PDX-derived models. We sought to understand the mechanisms underlying the differential responses and suggest a patient stratification strategy. Thermal proteome profiling (TPP) identified the protein targets of XL888 in a pair of sensitive and unresponsive cell lines. Unbiased proteomics and phosphoproteomics analyses identified CDK2 as a driver of resistance to both BRAF and Hsp90 inhibitors and its expression is regulated by the transcription factor MITF upon XL888 treatment. The CDK2 inhibitor, dinaciclib, attenuated resistance to both classes of inhibitors and combinations thereof. Notably, we found that MITF expression correlates with CDK2 upregulation in patients; thus, dinaciclib would warrant consideration for treatment of patients unresponsive to BRAF-MEK and/or Hsp90 inhibitors and/or harboring MITF amplification/overexpression. 

  • 192.
    B. Kumar, Ramakrishnan
    et al.
    Karolinska institutet, Sverige.
    Zhu, Lin
    KTH, Skolan för teknik och hälsa (STH), Naturvetenskap och biomedicin, Strukturell bioteknik.
    Hebert, Hans
    KTH, Skolan för teknik och hälsa (STH), Naturvetenskap och biomedicin, Strukturell bioteknik. Karolinska institutet, Sverige.
    Jegerschöld, Caroline
    Karolinska institutet, Sverige.
    Method to Visualize and Analyze Membrane Interacting Proteins by Transmission Electron Microscopy2017Inngår i: Journal of Visualized Experiments, ISSN 1940-087X, E-ISSN 1940-087X, nr 121, artikkel-id e55148Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Monotopic proteins exert their function when attached to a membrane surface, and such interactions depend on the specific lipid composition and on the availability of enough area to perform the function. Nanodiscs are used to provide a membrane surface of controlled size and lipid content. In the absence of bound extrinsic proteins, sodium phosphotungstate-stained nanodiscs appear as stacks of coins when viewed from the side by transmission electron microscopy (TEM). This protocol is therefore designed to intentionally promote stacking; consequently, the prevention of stacking can be interpreted as the binding of the membrane-binding protein to the nanodisc. In a further step, the TEM images of the protein-nanodisc complexes can be processed with standard single-particle methods to yield low-resolution structures as a basis for higher resolution cryoEM work. Furthermore, the nanodiscs provide samples suitable for either TEM or non-denaturing gel electrophoresis. To illustrate the method, Ca2+-induced binding of 5-lipoxygenase on nanodiscs is presented.

  • 193. Babrzadeh, F.
    et al.
    Varghese, V.
    Pacold, M.
    Liu, T. F.
    Nyrén, Pål
    KTH, Skolan för bioteknologi (BIO), Biokemi.
    Schiffer, C.
    Fessel, W. J.
    Shafer, R. W.
    Collinearity of protease mutations in HIV-1 samples with high-level protease inhibitor class resistance2013Inngår i: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 68, nr 2, s. 414-418Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objectives: To determine whether pan-protease inhibitor (PI)-resistant virus populations are composed predominantly of viruses with resistance to all PIs or of diverse virus populations with resistance to different subsets of PIs. Methods: We performed deep sequencing of plasma virus samples from nine patients with high-level genotypic and/or phenotypic resistance to all licensed PIs. The nine virus samples had a median of 12 PI resistance mutations by direct PCR Sanger sequencing. Results: For each of the nine virus samples, deep sequencing showed that each of the individual viruses within a sample contained nearly all of the mutations detected by Sanger sequencing. Indeed, a median of 94.9% of deep sequence reads had each of the PI resistance mutations present as a single chromatographic peak in the Sanger sequence. A median of 5.0% of reads had all but one of the Sanger mutations that were not part of an electrophoretic mixture. Conclusions: The collinearity of PI resistance mutations in the nine virus samples demonstrated that pan-PI-resistant viruses are able to replicate in vivo despite their highly mutated protease enzymes. We hypothesize that the marked collinearity of PI resistance mutations in pan-PI-resistant virus populations results from the unique requirements for multi-PI resistance and the extensive cross-resistance conferred by many of the accessory PI resistance mutations.

  • 194. Bachelet, Delphine
    et al.
    Hassler, Signe
    Mbogning, Cyprien
    Link, Jenny
    Ryner, Malin
    Ramanujam, Ryan
    KTH, Skolan för teknikvetenskap (SCI), Matematik (Inst.), Matematik (Avd.).
    Auer, Michael
    Jensen, Poul Erik Hyldgaard
    Koch-Henriksen, Nils
    Warnke, Clemens
    Ingenhoven, Kathleen
    Buck, Dorothea
    Grummel, Verena
    Lawton, Andy
    Donnellan, Naoimh
    Hincelin-Mery, Agnes
    Sikkema, Dan
    Pallardy, Marc
    Kieseier, Bernd
    Hemmer, Bernard
    Hartung, Hans Peter
    Sorensen, Per Soelberg
    Deisenhammer, Florian
    Donnes, Pierre
    Davidson, Julie
    Fogdell-Hahn, Anna
    Broet, Philippe
    Occurrence of Anti-Drug Antibodies against Interferon-Beta and Natalizumab in Multiple Sclerosis: A Collaborative Cohort Analysis2016Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, nr 11, artikkel-id e0162752Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Immunogenicity of biopharmaceutical products in multiple sclerosis is a frequent side effect which has a multifactorial etiology. Here we study associations between anti-drug antibody (ADA) occurrence and demographic and clinical factors. Retrospective data from routine ADA test laboratories in Sweden, Denmark, Austria and Germany (Dusseldorf group) and from one research study in Germany (Munich group) were gathered to build a collaborative multi-cohort dataset within the framework of the ABIRISK project. A subset of 5638 interferon-beta (IFN beta)-treated and 3440 natalizumab-treated patients having data on at least the first two years of treatment were eligible for interval-censored time-to-event analysis. In multivariate Cox regression, IFN beta-1a subcutaneous and IFN beta-1b subcutaneous treated patients were at higher risk of ADA occurrence compared to IFN beta-1a intramuscular-treated patients (pooled HR = 6.4, 95% CI 4.9-8.4 and pooled HR = 8.7, 95% CI 6.6-11.4 respectively). Patients older than 50 years at start of IFN beta therapy developed ADA more frequently than adult patients younger than 30 (pooled HR = 1.8, 95% CI 1.4-2.3). Men developed ADA more frequently than women (pooled HR = 1.3, 95% CI 1.1-1.6). Interestingly we observed that in Sweden and Germany, patients who started IFN beta in April were at higher risk of developing ADA (HR = 1.6, 95% CI 1.1-2.4 and HR = 2.4, 95% CI 1.5-3.9 respectively). This result is not confirmed in the other cohorts and warrants further investigations. Concerning natalizumab, patients older than 45 years had a higher ADA rate (pooled HR = 1.4, 95% CI 1.0-1.8) and women developed ADA more frequently than men (pooled HR = 1.4, 95% CI 1.0-2.0). We confirmed previously reported differences in immunogenicity of the different types of IFN beta. Differences in ADA occurrence by sex and age are reported here for the first time. These findings should be further investigated taking into account other exposures and biomarkers.

  • 195.
    Bachmann, Julie
    et al.
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Burte, Florence
    Pramana, Setia
    Conte, Ianina
    Brown, Biobele J.
    Orimadegun, Adebola E.
    Ajetunmobi, Wasiu A.
    Afolabi, Nathaniel K.
    Akinkunmi, Francis
    Omokhodion, Samuel
    Akinbami, Felix O.
    Shokunbi, Wuraola A.
    Kampf, Caroline
    Pawitan, Yudi
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Sodeinde, Olugbemiro
    Schwenk, Jochen M.
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Wahlgren, Mats
    Fernandez-Reyes, Delmiro
    Nilsson, Peter
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Affinity Proteomics Reveals Elevated Muscle Proteins in Plasma of Children with Cerebral Malaria2014Inngår i: PLoS Pathogens, ISSN 1553-7366, E-ISSN 1553-7374, Vol. 10, nr 4, s. e1004038-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Systemic inflammation and sequestration of parasitized erythrocytes are central processes in the pathophysiology of severe Plasmodium falciparum childhood malaria. However, it is still not understood why some children are more at risks to develop malaria complications than others. To identify human proteins in plasma related to childhood malaria syndromes, multiplex antibody suspension bead arrays were employed. Out of the 1,015 proteins analyzed in plasma from more than 700 children, 41 differed between malaria infected children and community controls, whereas 13 discriminated uncomplicated malaria from severe malaria syndromes. Markers of oxidative stress were found related to severe malaria anemia while markers of endothelial activation, platelet adhesion and muscular damage were identified in relation to children with cerebral malaria. These findings suggest the presence of generalized vascular inflammation, vascular wall modulations, activation of endothelium and unbalanced glucose metabolism in severe malaria. The increased levels of specific muscle proteins in plasma implicate potential muscle damage and microvasculature lesions during the course of cerebral malaria.

  • 196. Backvall, H.
    et al.
    Stromberg, S.
    Gustafsson, Anna
    KTH, Tidigare Institutioner, Bioteknologi.
    Asplund, A.
    Sivertsson, Åsa
    KTH, Tidigare Institutioner, Bioteknologi.
    Lundeberg, Joakim
    KTH, Tidigare Institutioner, Bioteknologi.
    Ponten, F.
    Mutation spectra of epidermal p53 clones adjacent to basal cell carcinoma and squamous cell carcinoma2004Inngår i: Experimental dermatology, ISSN 0906-6705, E-ISSN 1600-0625, Vol. 13, nr 10, s. 643-650Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Foci of normal keratinocytes overexpressing p53 protein are frequently found in normal human skin. Such epidermal p53 clones are common in chronically sun-exposed skin and have been suggested to play a role in skin cancer development. In the present study, we have analyzed the prevalence of p53 mutations in epidermal p53 clones from normal skin surrounding basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Using laser-assisted microdissection, 37 epidermal p53 clones adjacent to BCC (21) and SCC (16) were collected. Genetic analysis was performed using a multiplex/nested polymerase chain reaction followed by direct DNA sequencing of p53 exons 2-11. In total, 21 of 37 analyzed p53 clones consisted of p53-mutated keratinocytes. The identified mutations were located in p53 exons 4-8, corresponding to the sequence-specific DNA-binding domain. All mutations were missense, and 78% displayed a typical ultraviolet signature. The frequency of p53 mutations was similar in skin adjacent to BCC compared to SCC. The presented data confirm and extend previous knowledge on the genetic background of epidermal p53 clones. The mutation spectra found in epidermal p53 clones resemble that of non-melanoma skin cancer. Approximately, 40% of the epidermal p53 clones lacked an underlying p53 mutation, suggesting that other genetic events in genes up- or downstream of the p53 gene can generate foci of normal keratinocytes overexpressing p53 protein.

  • 197.
    Badal Tejedor, Maria
    et al.
    KTH, Skolan för kemivetenskap (CHE), Kemi, Yt- och korrosionsvetenskap. SP, Technical Research Institute of Sweden, Box 5607, SE-114 86 Stockholm, Swede.
    Nordgren, N.
    Schuleit, M.
    Rutland, Mark W.
    KTH, Skolan för kemivetenskap (CHE), Kemi, Yt- och korrosionsvetenskap. SP, Technical Research Institute of Sweden, Box 5607, SE-114 86 Stockholm, Swede.
    Millqvist-Fureby, A.
    Tablet mechanics depend on nano and micro scale adhesion, lubrication and structure2015Inngår i: International Journal of Pharmaceutics, ISSN 0378-5173, E-ISSN 1873-3476, Vol. 486, nr 1-2, s. 315-323Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Tablets are the most convenient form for drug administration. However, despite the ease of manufacturing problems such as powder adhesion occur during the production process. This study presents surface and structural characterization of tablets formulated with commonly used excipients (microcrystalline cellulose (MCC), lactose, mannitol, magnesium (Mg) stearate) pressed under different compaction conditions. Tablet surface analyses were performed with scanning electron microscopy (SEM), profilometry and atomic force microscopy (AFM). The mechanical properties of the tablets were evaluated with a tablet hardness test. Local adhesion detected by AFM decreased when Mg stearate was present in the formulation. Moreover, the tablet strength of plastically deformable excipients such as MCC was significantly decreased after addition of Mg stearate. Combined these facts indicate that Mg stearate affects the particle-particle bonding and thus elastic recovery. The MCC excipient also displayed the highest hardness which is characteristic for a highly cohesive material. This is discussed in the view of the relatively high adhesion found between MCC and a hydrophilic probe at the nanoscale using AFM. In contrast, the tablet strength of brittle materials like lactose and mannitol is unaffected by Mg stearate. Thus fracture occurs within the excipient particles and not at particle boundaries, creating new surfaces not previously exposed to Mg stearate. Such uncoated surfaces may well promote adhesive interactions with tools during manufacture.

  • 198.
    Badal Tejedor, Maria
    et al.
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Kemi, Yt- och korrosionsvetenskap. RISE Research Intitutes of Sweden.
    Pazesh, Samaneh
    Nordgren, Niklas
    Schuleit, Michael
    Rutland, Mark W.
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Kemi, Yt- och korrosionsvetenskap. RISE Research Intitutes of Sweden.
    Alderborn, Göran
    Millqvist-Fureby, Anna
    Milling induced amorphisation andrecrystallization of α-lactose monohydrate2018Inngår i: International Journal of Pharmaceutics, ISSN 0378-5173, E-ISSN 1873-3476, Vol. 537, nr 1-2, s. 140-147Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Preprocessing of pharmaceutical powders is a common procedure to condition the materials for a better manufacturing performance. However, such operations may induce undesired material properties modifications when conditioning particle size through milling, for example. Modification of both surface and bulk material structure will change the material properties, thus affecting the processability of the powder. Hence it is essential to control the material transformations that occur during milling. Topographical and mechanical changes in surface properties can be a preliminary indication of further material transformations. Therefore a surface evaluation of the alpha-lactose monohydrate after short and prolonged milling times has been performed. Unprocessed alpha-lactose monohydrate and spray dried lactose were evaluated in parallel to the milled samples as reference examples of the crystalline and amorphous lactose structure. Morphological differences between un-processed a-lactose, 1 h and 20 h milled lactose and spray dried lactose were detected from SEM and AFM images. Additionally, AFM was used to simultaneously characterize particle surface amorphicity by measuring energy dissipation. Extensive surface amorphicity was detected after 1 h of milling while prolonged milling times showed only a moderate particle surface amorphisation. Bulk material characterization performed with DSC indicated a partial amorphicity for the 1 h milled lactose and a fully amorphous thermal profile for the 20 h milled lactose. The temperature profiles however, were shifted somewhat in the comparison to the amorphous reference, particularly after extended milling, suggesting a different amorphous state compared to the spraydried material. Water loss during milling was measured with TGA, showing lower water content for the lactose amorphized through milling compared to spray dried amorphous lactose. The combined results suggest a surface-bulk propagation of the amorphicity during milling in combination with a different amorphous structural conformation to that of the amorphous spray dried lactose. The hardened surface may be due to either surface crystallization of lactose or to formation of a low-water glass transition.

  • 199. Baer, R
    et al.
    Eiken, Ola
    Karolinska Institutet.
    Effects of continuous positive- and negative-pressure breathing on the pattern of breathing in man during exercise.1989Inngår i: Acta Physiologica Scandinavica, ISSN 0001-6772, E-ISSN 1365-201X, Vol. 137, nr 2, s. 301-7Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Breathing pattern and static lung volumes were studied in 10 subjects at rest and during incremental-load cycle ergometry under three different conditions, viz. with normal pressure in the airways (control) and during continuous positive- and negative-pressure breathing (CPPB, CNPB) of +15 and -15 cmH2O. End-expiratory, end-inspiratory and mid-expiratory volumes were increased by CPPB and decreased by CNPB; these effects were especially pronounced at rest and during mild exercise. Both at rest and during exercise mean inspiratory flow (VT/TI) was exaggerated by CPPB and attenuated by CNPB. At rest these changes were due mainly to concomitant changes in tidal volume (VT) which was increased by CPPB and decreased by CNPB, while inspiratory time duration (TI) was relatively unaffected by pressure breathing. The transition from rest to loadless pedalling induced an increase in VT but no change in TI in the control condition, whereas in the CPPB and CNPB conditions TI decreased and VT remained unaltered. This CPPB- and CNPB-induced change in the volume-time threshold relationship at the onset of pedalling is attributed to increased stretch receptor activity in the extrathoracic portion of the trachea as a result of the increments in transmural pressure. During the course of exercise there was an inverse relationship between the slope of the VT-TI curve and the mid-expiratory volume in that the slope was greater in the control than in the CPPB condition and greatest during CNPB, suggesting that in exercise hyperpnoea the VT-TI relationship is also determined by pulmonary and/or thoracic wall stretch receptors capable of sensing the absolute lung volume.

  • 200. Baer, R.
    et al.
    Eiken, Ola
    Karolinska Institutet.
    Balldin, U.
    Cardiovascular effects of head-up tilt as affected by a vasopressin analogue1987Inngår i: The Physiologist, ISSN 0031-9376, E-ISSN 1522-1202, Vol. 30, nr 1 Suppl, s. S64-65Artikkel i tidsskrift (Fagfellevurdert)
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