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  • 151.
    Ahlner, Alexandra
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Molekylär Bioteknik. Linköpings universitet, Tekniska högskolan.
    Carlsson, Mats
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Molekylär Bioteknik. Linköpings universitet, Tekniska högskolan.
    Jonsson, Bengt-Harald
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Molekylär Bioteknik. Linköpings universitet, Tekniska högskolan.
    Lundström, Patrik
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Molekylär Bioteknik. Linköpings universitet, Tekniska högskolan.
    PINT: a software for integration of peak volumes and extraction of relaxation rates2013Ingår i: Journal of Biomolecular NMR, ISSN 0925-2738, E-ISSN 1573-5001, Vol. 56, nr 3, s. 191-202Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We present the software Peak INTegration (PINT), designed to perform integration of peaks in NMR spectra. The program is very simple to run, yet powerful enough to handle complicated spectra. Peaks are integrated by fitting predefined line shapes to experimental data and the fitting can be customized to deal with, for instance, heavily overlapped peaks. The results can be inspected visually, which facilitates systematic optimization of the line shape fitting. Finally, integrated peak volumes can be used to extract parameters such as relaxation rates and information about low populated states. The utility of PINT is demonstrated by applications to the 59 residue SH3 domain of the yeast protein Abp1p and the 289 residue kinase domain of murine EphB2.

  • 152.
    Ahlstrand, Erik
    et al.
    Örebro universitet, Institutionen för hälsovetenskap och medicin. Region Örebro län. Department of Medicine, Hematology, Örebro University Hospital, Örebro, Sweden.
    Bäckman, Anders
    Örebro universitet, Institutionen för medicinska vetenskaper. Clinical Research Centre, Örebro University Hospital, Örebro, Sweden.
    Persson, Lennart
    Region Örebro län. Department of Infectious diseases, Örebro University Hospital, Örebro, Sweden.
    Mölling, Paula
    Region Örebro län. Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Tidefelt, Ulf
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Söderquist, Bo
    Örebro universitet, Institutionen för hälsovetenskap och medicin. Department of Infectious diseases & Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Evaluation of a PCR method to determine the clinical significance of blood cultures with Staphylococcus epidermidis in patients with hematological malignancies2014Ingår i: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 122, nr 6, s. 539-544Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The aim was to investigate whether the detection and quantification of Staphylococcus epidermidis DNA in blood could distinguish S. epidermidis blood stream infections (BSIs) from blood culture contaminations in patients with hematological malignancies. The hld gene was chosen to identify S. epidermidis DNA and DNA in blood samples was detected by real-time PCR. Blood samples were obtained simultaneously with blood cultures positive for S. epidermidis (n = 30), during blood culture-negative episodes (n = 10) and episodes of bacteremia with other bacteria than S. epidermidis (n = 4) and from healthy blood donors (n = 10). In addition, DNA from S. epidermidis and a selection of other bacterial species were analyzed. Three different sets of criteria were used to classify episodes with positive blood cultures with S. epidermidis as BSIs or contaminations. All DNA preparations from S. epidermidis (n = 48) were hld-positive, but other bacterial species (n = 13) were negative. Sixteen (53%) of 30 blood samples from patients with blood cultures positive for S. epidermidis were hld-positive, but none of the controls. There was no clear association between a positive hld PCR and episodes interpreted as BSIs. In conclusion, hld PCR failed to distinguish S. epidermidis BSIs from blood culture contaminations in patients with hematological malignancies.

  • 153.
    Ahlstrand, I.
    et al.
    School of Health Sciences, Jönköping University, Jönköping, Sweden.
    Thyberg, Ingrid
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Reumatologiska kliniken i Östergötland.
    Falkmer, Torbjörn
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Smärt och rehabiliteringscentrum. School of Health Sciences, Jönköping University, Jönköping, Sweden; School of Occupational Therapy and Social Work, CHIRI, Curtin University, Perth, WA, Australia.
    Dahlström, Örjan
    Linköpings universitet, Institutionen för beteendevetenskap och lärande, Handikappvetenskap. Linköpings universitet, Filosofiska fakulteten. Linköpings universitet, Institutet för handikappvetenskap (IHV).
    Björk, Mathilda
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Rehabenheten. School of Health Sciences, Jönköping University, Jönköping, Sweden.
    Pain and activity limitations in women and men with contemporary treated early RA compared to 10 years ago: the Swedish TIRA project2015Ingår i: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 44, nr 4, s. 259-264Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives: To study differences regarding pain and activity limitations during the 3 years following diagnosis in women and men with contemporary treated early RA compared with their counterparts who were diagnosed 10 years earlier. Method: This study was based on patients recruited to the Early Intervention in RA (TIRA) project. In the first cohort (TIRA-1) 320 patients were included in time for diagnosis during 1996-1998 and 463 patients were included in the second cohort (TIRA-2) during 2006-2009. Disease activity, pain intensity (Visual Analogue Scale, VAS), bodily pain (BP) in the 36-item Short Form Health Survey (SF-36), activity limitations (Health Assessment Questionnaire, HAQ), and medication were reported at inclusion and at follow-up after 1, 2, and 3 years. Results: Disease activity, pain, and activity limitations were pronounced at inclusion across both genders and in both cohorts, with some improvement observed during the first year after diagnosis. Disease activity did not differ between cohorts at inclusion but was significantly lower at the follow-ups in the TIRA-2 cohort, in which the patients were prescribed traditional disease-modifying anti-rheumatic drugs (DMARDs) and biological agents more frequently. In TIRA-2, patients reported significantly lower pain and activity limitations at all follow-ups, with men reporting lower pain than women. Women reported significantly higher activity limitations at all time points in TIRA-2. Conclusions: Pain and activity limitations were still pronounced in the contemporary treated early RA cohort compared with their counterparts diagnosed 10 years earlier and both of these factors need to be addressed in clinical settings.

  • 154.
    Ahlstrand, Inger
    et al.
    Jonköping University, Sweden.
    Björk, Mathilda
    Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Rehabenheten. Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Jonköping University, Sweden.
    Thyberg, Ingrid
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Reumatologiska kliniken i Östergötland.
    Falkmer, Torbjörn
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Smärt och rehabiliteringscentrum. Jonköping University, Sweden; Curtin University, Australia.
    Pain and difficulties performing valued life activities in women and men with rheumatoid arthritis2015Ingår i: Clinical Rheumatology, ISSN 0770-3198, E-ISSN 1434-9949, Vol. 34, nr 8, s. 1353-1362Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    This study aimed to examine the difficulties with performing valued life activities in relation to pain intensity in women and men with rheumatoid arthritis (RA). In total, 737 persons with RA (73 % women) from three rheumatology units in Sweden responded to a questionnaire measuring performance of 33 valued life activities and self-rated pain. The relationships between performance of valued life activities (VLAs) and pain (measured by visual analogue scale (VAS)) were analysed based on gender. Multiple linear regression analyses were conducted with the total VLA score as dependent variable. Women reported more pain and difficulties in performing valued life activities than men. Across genders, 85 % reported at least one valued life activity affected by RA. Significantly more women than men encountered difficulties in performing some activities such as cooking, gardening and meeting new people. Women reported higher pain intensity (35 mm) than men (31 mm). Almost all 33 difficulty ratings for valued life activities were higher among persons with high pain (greater than 40 mm) than persons with lower pain. Difficulty ratings for valued life activities correlated positively with pain in persons with lower pain, but not among those with high pain. The results highlight the importance of addressing pain, especially among women with RA, as they reported pain to impact on their valued life activities. Interestingly, this was evident also in women with lower levels of pain.

  • 155. Ahlstrand, Tuuli
    et al.
    Torittu, Annamari
    Elovaara, Heli
    Välimaa, Hannamari
    Pöllänen, Marja T.
    Kasvandik, Sergo
    Högbom, Martin
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
    Ihalin, Riikka
    Interactions between the Aggregatibacter actinomycetemcomitans secretin HofQ and host cytokines indicate a link between natural competence and interleukin-8 uptake2018Ingår i: Virulence, ISSN 2150-5594, E-ISSN 2150-5608, Vol. 9, nr 1, s. 1205-1223Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Naturally competent bacteria acquire DNA from their surroundings to survive in nutrient-poor environments and incorporate DNA into their genomes as new genes for improved survival. The secretin HofQ from the oral pathogen Aggregatibacter actinomycetemcomitans has been associated with DNA uptake. Cytokine sequestering is a potential virulence mechanism in various bacteria and may modulate both host defense and bacterial physiology. The objective of this study was to elucidate a possible connection between natural competence and cytokine uptake in A. actinomycetemcomitans. The extramembranous domain of HofQ (emHofQ) was shown to interact with various cytokines, of which IL-8 exhibited the strongest interaction. The dissociation constant between emHofQ and IL-8 was 43nM in static settings and 2.4M in dynamic settings. The moderate binding affinity is consistent with the hypothesis that emHofQ recognizes cytokines before transporting them into the cells. The interaction site was identified via crosslinking and mutational analysis. By structural comparison, relateda type I KH domain with a similar interaction site was detected in the Neisseria meningitidis secretin PilQ, which has been shown to participate in IL-8 uptake. Deletion of hofQ from the A. actinomycetemcomitans genome decreased the overall biofilm formation of this organism, abolished the response to cytokines, i.e., decreased eDNA levels in the presence of cytokines, and increased the susceptibility of the biofilm to tested -lactams. Moreover, we showed that recombinant IL-8 interacted with DNA. These results can be used in further studies on the specific role of cytokine uptake in bacterial virulence without interfering with natural-competence-related DNA uptake.

  • 156.
    Ahlstrom, Christina A.
    et al.
    US Geol Survey, AK 99508 USA.
    Bonnedahl, Jonas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten. Kalmar Cty Hosp, Sweden.
    Woksepp, Hanna
    Kalmar Cty Hosp, Sweden.
    Hernandez, Jorge
    Uppsala Univ, Sweden.
    Olsen, Bjorn
    Uppsala Univ, Sweden.
    Ramey, Andrew M.
    US Geol Survey, AK 99508 USA.
    Acquisition and dissemination of cephalosporin-resistant E.coli in migratory birds sampled at an Alaska landfill as inferred through genomic analysis2018Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, artikel-id 7361Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Antimicrobial resistance (AMR) in bacterial pathogens threatens global health, though the spread of AMR bacteria and AMR genes between humans, animals, and the environment is still largely unknown. Here, we investigated the role of wild birds in the epidemiology of AMR Escherichia coli. Using next-generation sequencing, we characterized cephalosporin-resistant E. coli cultured from sympatric gulls and bald eagles inhabiting a landfill habitat in Alaska to identify genetic determinants conferring AMR, explore potential transmission pathways of AMR bacteria and genes at this site, and investigate how their genetic diversity compares to isolates reported in other taxa. We found genetically diverse E. coli isolates with sequence types previously associated with human infections and resistance genes of clinical importance, including blaCTX-M and blaCMY. Identical resistance profiles were observed in genetically unrelated E. coli isolates from both gulls and bald eagles. Conversely, isolates with indistinguishable core-genomes were found to have different resistance profiles. Our findings support complex epidemiological interactions including bacterial strain sharing between gulls and bald eagles and horizontal gene transfer among E. coli harboured by birds. Results suggest that landfills may serve as a source for AMR acquisition and/or maintenance, including bacterial sequence types and AMR genes relevant to human health.

  • 157.
    Ahlsén, Göran
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för naturvetenskaplig biokemi.
    Hultén, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi.
    Shuman, Cynthia
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för naturvetenskaplig biokemi.
    Poliakov, Anton
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för naturvetenskaplig biokemi.
    Lindgren, Maria T.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för naturvetenskaplig biokemi.
    Alterman, Mathias
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi.
    Samuelsson, Bertil
    Hallberg, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi.
    Danielson, U. Helena
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för naturvetenskaplig biokemi.
    Resistance profiles of cyclic and linear inhibitors of HIV-1 protease2002Ingår i: Antiviral Chemistry & Chemotherapy, ISSN 0956-3202, E-ISSN 2040-2066, Vol. 13, nr 1, s. 27-37Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Resistance to anti-HIV protease drugs is a major problem in the design of AIDS drugs with long-term efficacy. To identify structural features associated with a certain resistance profile, the inhibitory properties of a series of symmetric and asymmetric cyclic sulfamide, cyclic urea and linear transition-state analogue inhibitors of HIV-1 protease were investigated using wild-type and mutant enzyme. To allow a detailed structure-inhibition analysis, enzyme with single, double, triple and quadruple combinations of G48V, V82A, 184V and L90M substitutions was used. Kinetic analysis of the mutants revealed that catalytic efficiency was 1-30% of that for the wild-type enzyme, a consequence of reduced kcat in all cases and an increased KM for all mutants except for the G48V enzyme. The overall structure-inhibitory profiles of the cyclic compounds were similar, and the inhibition of the V82A, 184V and G48V/L90M mutants were less efficient than of the wild-type enzyme. The greatest increase in Ki was generally observed for the 184V mutant and least for the G48V/L90M mutant, and additional combinations of mutations did not result in improved inhibition profiles for the cyclic compounds. An extended analysis of additional mutants, and including a set of linear compounds, showed that the profile was unique for each compound, and did not reveal any general structural features associated with a certain inhibition profile. The effects of structural modifications in the inhibitors, or of mutations, were not additive and they differed depending on their context. The results demonstrate the difficulties in predicting resistance, even for closely related compounds, and designing compounds with improved resistance profiles.

  • 158.
    Ahluwalia, Bani
    et al.
    Department of Microbiology and Immunology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden / Calmino Group AB, Sahlgrenska Science Park, Gothenburg, Sweden.
    Magnusson, Maria K.
    Department of Microbiology and Immunology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden / Department of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    Isaksson, Stefan
    Department of Microbiology and Immunology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden / Department of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    Larsson, Fredrik
    Department of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    Öhman, Lena
    Department of Microbiology and Immunology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden / Department of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    Effects of Aloe barbadensis Mill. extract (AVH200®) on human blood T cell activity in vitro2016Ingår i: Journal of Ethnopharmacology, ISSN 0378-8741, E-ISSN 1872-7573, Vol. 179, s. 301-309Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    ETHNOPHARMACOLOGICAL RELEVANCE: Aloe barbadensis Mill. (Aloe vera) is a widely used medicinal plant well reputed for its diverse therapeutic applications. It has been used for thousands of years in folk medicine to treat various conditions and the Aloe vera gel has been reported to possess anti-inflammatory as well as immunostimulatory and immunomodulatory properties. However, the mode of action is still unclear.

    AIM OF THE STUDY: The aim of this study was determine the effects of two well-defined A. barbadensis Mill. extracts AVH200® and AVE200 on human blood T cells in vitro.

    MATERIALS AND METHODS: Peripheral blood mononuclear cells (PBMC) from healthy donors were stimulated polyclonally in the presence or absence of AVH200® and AVE200. The T cell phenotype was investigated by flow cytometry, cell proliferation was determined by CFSE dye and thymidine assay, respectively and cytokine secretion was determined by MSD® Multi-Spot Assay system and ELISA.

    RESULTS: The presence of AVH200® resulted in a reduced expression of CD25 among CD3(+) T cells and suppression of T cell proliferation in a dose dependent manner. Furthermore, AVH200® reduced the expression of CD28 on CD3(+) T cells. AVH200® also reduced the secretion of IL-2, IFN-γ and IL-17A in PBMC cultures. The AVH200® dose dependent reduction in T cell activation and proliferation recorded in the cell cultures was not due to apoptosis or cell death. Additionally, AVH200® was found to be more effective as compared to AVE200 in reducing T cell activation and proliferation.

    CONCLUSION: AVH200® has the potential to reduce the activation, proliferation and cytokine secretion of healthy human blood T cells. Our study suggests that AVH200® has a suppressive effect on human blood T cells in vitro.

  • 159.
    Ahlén, Caroline
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Outcome of patients with severe aortic stenosis – A retrospective follow-up study2008Självständigt arbete på grundnivå (kandidatexamen), 10 poäng / 15 hpStudentuppsats
    Abstract [en]

    Aortic stenosis is the most common valvular disease in the adult population. A significant aortic stenosis is a serious condition, and if a symptomatic patient is not operated on, it may in most cases cause death. We have examined how many aortic stenoses that were diagnosed during one year, and a follow-up of the patients was also performed. We found 77 patients with significant aortic stenosis with a mean age of 76±13 years. At the time of follow-up 30 (39%) patients, aged between 29-85 years, had been surgically treated with implantation of a valve prosthesis within 2-23 months after the initial examination. At this initial examination 14 of the 30 patients who later underwent surgery had no symptoms. A coronary bypass operation was also performed on seven patients. Postoperative complications were observed in six patients, but none of them was fatal. At the initial examinations there were 26 (34%) patients with a significant aortic stenosis and symptoms who were not treated surgically. The main reason why these patients were not operated was high age, unwillingness, or severe left ventricular dysfunction. This study indicates the importance of repeated clinical and echocardiograpic examinations in patients with aortic stenosis. Almost half of the patients, that later underwent surgery, had no symptoms at the initial examination, but later developed symptoms which made surgery necessary. In one third of the patients no surgery was performed in spite of clinical symptoms.

  • 160.
    Ahmad, Abdulbaghi
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap.
    Children of Kurdistan: Survivors of trauma and terror2000Ingår i: Child suffering in the world: Child maltreatment by parents, culture and governments in different countries and cultures / [ed] Marvasti JA, New York: 010 Publishers, 2000, s. 153-177Kapitel i bok, del av antologi (Refereegranskat)
  • 161.
    Ahmad, Abdulbaghi
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap.
    von Knorring, Anne-Liis
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap.
    Tiden läkar inte alla sår2002Ingår i: Stress: molekylerna, individen, organisationen samhället / [ed] Ekman R & Arnetz B, Liber, 2002, 1Kapitel i bok, del av antologi (Refereegranskat)
  • 162. Ahmad, Abdulbaghi
    et al.
    von Knorring, Anne-Liis
    Tiden läkar inte alla sår2006Ingår i: Stress, molekyl, individ, organisation och samhälle / [ed] Ekman R & Arnetz B, Liber, 2006, 2, s. 128-138Kapitel i bok, del av antologi (Refereegranskat)
  • 163.
    Ahmad, Abrar
    et al.
    Region Örebro län. Department of Clinical Research, Örebro University Hospital, Örebro, Sweden.
    Venizelos, Nikolaos
    Department of Clinical Research, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Hahn-Strömberg, Victoria
    Region Örebro län. Department of Clinical Research, Örebro University Hospital, Örebro, Sweden; ; Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden.
    Prognostic Effect of Vascular Endothelial Growth Factor +936C/T Polymorphism on Tumor Growth Pattern and Survival in Patients Diagnosed with Colon Carcinoma2016Ingår i: Journal of Tumor Research, Vol. 2, nr 1, s. 1-6, artikel-id 1000108Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction: Vascular endothelial growth factor (VEGF) is considered as endothelial cell-specific mitogen that plays an important role in the process of angiogenesis, thereby affecting the prognosis of tumor as angiogenesis is a crucial phase in tumor growth and metastasis. Accordingly, we carried out a case-control study to assess whether VEGF rs3025039 polymorphism affects the growth pattern and susceptibility to colon carcinoma.

    Materials and methods: One hundred and fifty, formalin fixed paraffin embedded (FFPE) tissue samples from patients diagnosed with colon carcinoma and the same number of blood controls were used in the present study. VEGF +936 C>T (rs3025039) polymorphism was evaluated by pyrosequencing. Computer image analysis was used to analyse the growth pattern of the colon carcinoma tumor by using cytokeratin-8 stained slides.

    Results: A heterozygous genotype TC in rs3025039 polymorphism was found as a significantly protective genotype as compared to homozygous genotypes (CC and TT). However we found no significant correlation between investigated polymorphisms, tumor growth pattern, 5 years survival and other clinicopathological parameters.

    Conclusion: We concluded that the heterogenous genotype of VEGF rs3025039 polymorphism appears to be a protective factor for colon carcinoma that could be a useful marker in follow-up studies and may be a genetic determinant for colon carcinoma.

  • 164.
    Ahmad, Irfan
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet; Department of Allied Health Sciences, University of Health Sciences.
    Cimdins, Annika
    Beske, Timo
    Römling, Ute
    Detailed analysis of c-di-GMP mediated regulation of csgD expression in Salmonella typhimurium2017Ingår i: BMC Microbiology, ISSN 1471-2180, E-ISSN 1471-2180, Vol. 17, artikel-id 27Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The secondary messenger cyclic di-GMP promotes biofilm formation by up regulating the expression of csgD, encoding the major regulator of rdar biofilm formation in Salmonella typhimurium. The GGDEF/EAL domain proteins regulate the c-di-GMP turnover. There are twenty-two GGDEF/EAL domain proteins in the genome of S. typhimurium. In this study, we dissect the role of individual GGDEF/EAL proteins for csgD expression and rdar biofilm development. Results: Among twelve GGDEF domains, two proteins upregulate and among fifteen EAL domains, four proteins down regulate csgD expression. We identified two additional GGDEF proteins required to promote optimal csgD expression. With the exception of the EAL domain of STM1703, solely, diguanylate cyclase and phosphodiesterase activities are required to regulate csgD mediated rdar biofilm formation. Identification of corresponding phosphodiesterases and diguanylate cyclases interacting in the csgD regulatory network indicates various levels of regulation by c-di-GMP. The phosphodiesterase STM1703 represses transcription of csgD via a distinct promoter upstream region. Conclusion: The enzymatic activity and the protein scaffold of GGDEF/EAL domain proteins regulate csgD expression. Thereby, c-di-GMP adjusts csgD expression at multiple levels presumably using a multitude of input signals.

  • 165. Ahmad, Shafqat
    et al.
    Mora, Samia
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA; Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Clinical Research Centre, Lund University, Skåne University Hospital, Malmö, Sweden.
    Orho-Melander, Marju
    Ridker, Paul M.
    Hu, Frank B.
    Chasman, Daniel I.
    Adiposity and Genetic Factors in Relation to Triglycerides and Triglyceride-Rich Lipoproteins in the Women's Genome Health Study2018Ingår i: Clinical Chemistry, ISSN 0009-9147, E-ISSN 1530-8561, Vol. 64, nr 1, s. 231-241Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Previous results from Scandinavian cohorts have shown that obesity accentuates the effects of common genetic susceptibility variants on increased triglycerides (TG). Whether such interactions are present in the US population and further selective for particular TG-rich lipoprotein subfractions is unknown.

    METHODS: We examined these questions using body mass index (BMI) and waist circumference (WC) among women of European ancestry from the Women's Genome Health Study (WGHS) (n = 21840 for BMI; n = 19313 for WC). A weighted genetic risk score (TG-wGRS) based on 40 published TG-associated single-nucleotide polymorphisms was calculated using published effect estimates.

    RESULTS: Comparing overweight (BMI ≥ 25 kg/m2) and normal weight (BMI < 25 kg/m2) WGHS women, each unit increase of TG-wGRS was associated with TG increases of 1.013% and 1.011%, respectively, and this differential association was significant (Pinteraction = 0.014). Metaanalyses combining results for WGHS BMI with the 4 Scandinavian cohorts (INTER99, HEALTH2006, GLACIER, MDC) (total n = 40026) yielded a more significant interaction (Pinteraction = 0.001). Similarly, we observed differential association of the TG-wGRS with TG (Pinteraction = 0.006) in strata of WC (<80 cm vs ≥80 cm). Metaanalysis with 2 additional cohorts reporting WC (INTER99 and HEALTH2006) (total n = 27834) was significant with consistent effects (Pinteraction = 0.006). We also observed highly significant interactions of the TG-wGRS across the strata of BMI with very large, medium, and small TG-rich lipoprotein subfractions measured by nuclear magnetic resonance spectroscopy (all Pinteractions < 0.0001). The differential effects were strongest for very large TG-rich lipoprotein.

    CONCLUSIONS: Our results support the original findings and suggest that obese individuals may be more susceptible to aggregated genetic risk associated with common TG-raising alleles, with effects accentuated in the large TG-rich lipoprotein subfraction.

  • 166. Ahmad, Shafqat
    et al.
    Mora, Samia
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA; Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Clinical Research Centre, Lund University, Skåne University Hospital, Malmö, Sweden.
    Orho-Melander, Marju
    Ridker, Paul M.
    Hu, Frank B.
    Chasman, Daniel I.
    Adiposity and Genetic Factors in Relation to Triglycerides and Triglyceride-Rich Lipoproteins in the Women's Genome Health Study2018Ingår i: Clinical Chemistry, ISSN 0009-9147, E-ISSN 1530-8561, Vol. 64, nr 1, s. 231-241Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Previous results from Scandinavian cohorts have shown that obesity accentuates the effects of common genetic susceptibility variants on increased triglycerides (TG). Whether such interactions are present in the US population and further selective for particular TG-rich lipoprotein subfractions is unknown.

    METHODS: We examined these questions using body mass index (BMI) and waist circumference (WC) among women of European ancestry from the Women's Genome Health Study (WGHS) (n = 21840 for BMI; n = 19313 for WC). A weighted genetic risk score (TG-wGRS) based on 40 published TG-associated single-nucleotide polymorphisms was calculated using published effect estimates.

    RESULTS: Comparing overweight (BMI ≥ 25 kg/m2) and normal weight (BMI < 25 kg/m2) WGHS women, each unit increase of TG-wGRS was associated with TG increases of 1.013% and 1.011%, respectively, and this differential association was significant (Pinteraction = 0.014). Metaanalyses combining results for WGHS BMI with the 4 Scandinavian cohorts (INTER99, HEALTH2006, GLACIER, MDC) (total n = 40026) yielded a more significant interaction (Pinteraction = 0.001). Similarly, we observed differential association of the TG-wGRS with TG (Pinteraction = 0.006) in strata of WC (<80 cm vs ≥80 cm). Metaanalysis with 2 additional cohorts reporting WC (INTER99 and HEALTH2006) (total n = 27834) was significant with consistent effects (Pinteraction = 0.006). We also observed highly significant interactions of the TG-wGRS across the strata of BMI with very large, medium, and small TG-rich lipoprotein subfractions measured by nuclear magnetic resonance spectroscopy (all Pinteractions < 0.0001). The differential effects were strongest for very large TG-rich lipoprotein.

    CONCLUSIONS: Our results support the original findings and suggest that obese individuals may be more susceptible to aggregated genetic risk associated with common TG-raising alleles, with effects accentuated in the large TG-rich lipoprotein subfraction.

  • 167. Ahmad, Shafqat
    et al.
    Mora, Samia
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA; Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Clinical Research Centre, Lund University, Skåne University Hospital, Malmö, Sweden.
    Orho-Melander, Marju
    Ridker, Paul M.
    Hu, Frank B.
    Chasman, Daniel I.
    Adiposity and Genetic Factors in Relation to Triglycerides and Triglyceride-Rich Lipoproteins in the Women's Genome Health Study2018Ingår i: Clinical Chemistry, ISSN 0009-9147, E-ISSN 1530-8561, Vol. 64, nr 1, s. 231-241Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Previous results from Scandinavian cohorts have shown that obesity accentuates the effects of common genetic susceptibility variants on increased triglycerides (TG). Whether such interactions are present in the US population and further selective for particular TG-rich lipoprotein subfractions is unknown.

    METHODS: We examined these questions using body mass index (BMI) and waist circumference (WC) among women of European ancestry from the Women's Genome Health Study (WGHS) (n = 21840 for BMI; n = 19313 for WC). A weighted genetic risk score (TG-wGRS) based on 40 published TG-associated single-nucleotide polymorphisms was calculated using published effect estimates.

    RESULTS: Comparing overweight (BMI ≥ 25 kg/m2) and normal weight (BMI < 25 kg/m2) WGHS women, each unit increase of TG-wGRS was associated with TG increases of 1.013% and 1.011%, respectively, and this differential association was significant (Pinteraction = 0.014). Metaanalyses combining results for WGHS BMI with the 4 Scandinavian cohorts (INTER99, HEALTH2006, GLACIER, MDC) (total n = 40026) yielded a more significant interaction (Pinteraction = 0.001). Similarly, we observed differential association of the TG-wGRS with TG (Pinteraction = 0.006) in strata of WC (<80 cm vs ≥80 cm). Metaanalysis with 2 additional cohorts reporting WC (INTER99 and HEALTH2006) (total n = 27834) was significant with consistent effects (Pinteraction = 0.006). We also observed highly significant interactions of the TG-wGRS across the strata of BMI with very large, medium, and small TG-rich lipoprotein subfractions measured by nuclear magnetic resonance spectroscopy (all Pinteractions < 0.0001). The differential effects were strongest for very large TG-rich lipoprotein.

    CONCLUSIONS: Our results support the original findings and suggest that obese individuals may be more susceptible to aggregated genetic risk associated with common TG-raising alleles, with effects accentuated in the large TG-rich lipoprotein subfraction.

  • 168. Ahmad, Shafqat
    et al.
    Rukh, Gull
    Varga, Tibor V
    Ali, Ashfaq
    Kurbasic, Azra
    Shungin, Dmitry
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Umeå universitet, Medicinska fakulteten, Institutionen för odontologi. Lund University.
    Ericson, Ulrika
    Koivula, Robert W
    Chu, Audrey Y
    Rose, Lynda M
    Ganna, Andrea
    Qi, Qibin
    Stancakova, Alena
    Sandholt, Camilla H
    Elks, Cathy E
    Curhan, Gary
    Jensen, Majken K
    Tamimi, Rulla M
    Allin, Kristine H
    Jorgensen, Torben
    Brage, Soren
    Langenberg, Claudia
    Aadahl, Mette
    Grarup, Niels
    Linneberg, Allan
    Pare, Guillaume
    Magnusson, Patrik KE
    Pedersen, Nancy L
    Boehnke, Michael
    Hamsten, Anders
    Mohlke, Karen L
    Pasquale, Louis T
    Pedersen, Oluf
    Scott, Robert A
    Ridker, Paul M
    Ingelsson, Erik
    Laakso, Markku
    Hansen, Torben
    Qi, Lu
    Wareham, Nicholas J
    Chasman, Daniel I
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning. Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning.
    Hu, Frank B
    Renström, Frida
    Orho-Melander, Marju
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Lund University and Harvard University.
    Gene x physical activity interactions in obesity: combined analysis of 111,421 individuals of European ancestry2013Ingår i: PLOS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 9, nr 7, s. e1003607-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Numerous obesity loci have been identified using genome-wide association studies. A UK study indicated that physical activity may attenuate the cumulative effect of 12 of these loci, but replication studies are lacking. Therefore, we tested whether the aggregate effect of these loci is diminished in adults of European ancestry reporting high levels of physical activity. Twelve obesity-susceptibility loci were genotyped or imputed in 111,421 participants. A genetic risk score (GRS) was calculated by summing the BMI-associated alleles of each genetic variant. Physical activity was assessed using self-administered questionnaires. Multiplicative interactions between the GRS and physical activity on BMI were tested in linear and logistic regression models in each cohort, with adjustment for age, age(2), sex, study center (for multicenter studies), and the marginal terms for physical activity and the GRS. These results were combined using meta-analysis weighted by cohort sample size. The meta-analysis yielded a statistically significant GRS x physical activity interaction effect estimate (P-interaction = 0.015). However, a statistically significant interaction effect was only apparent in North American cohorts (n = 39,810, P-interaction = 0.014 vs. n = 71,611, P-interaction = 0.275 for Europeans). In secondary analyses, both the FTO rs1121980 (P-interaction = 0.003) and the SEC16B rs10913469 (P-interaction = 0.025) variants showed evidence of SNP x physical activity interactions. This meta-analysis of 111,421 individuals provides further support for an interaction between physical activity and a GRS in obesity disposition, although these findings hinge on the inclusion of cohorts from North America, indicating that these results are either population-specific or non-causal.

  • 169. Ahmad, Shafqat
    et al.
    Varga, Tibor V
    Franks, Paul W
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Gene x environment interactions in obesity: the state of the evidence2013Ingår i: Human Heredity, ISSN 0001-5652, E-ISSN 1423-0062, Vol. 75, nr 2-4, s. 106-115Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background/Aims: Obesity is a pervasive and highly prevalent disease that poses substantial health risks to those it affects. The rapid emergence of obesity as a global epidemic and the patterns and distributions of the condition within and between populations suggest that interactions between inherited biological factors (e.g. genes) and relevant environmental factors (e.g. diet and physical activity) may underlie the current obesity epidemic.

    Methods: We discuss the rationale for the assertion that gene x lifestyle interactions cause obesity, systematically appraise relevant literature, and consider knowledge gaps future studies might seek to bridge. Results: We identified >200 relevant studies, of which most are relatively small scale and few provide replication data.

    Conclusion: Although studies on gene x lifestyle interactions in obesity point toward the presence of such interactions, improved data standardization, appropriate pooling of data and resources, innovative study designs, and the application of powerful statistical methods will be required if translatable examples of gene x lifestyle interactions in obesity are to be identified. Future studies, of which most will be observational, should ideally be accompanied by appropriate replication data and, where possible, by analogous findings from experimental settings where clinically relevant traits (e.g. weight regain and weight cycling) are outcomes.

    (C) 2013 S. Karger AG, Basel

  • 170.
    Ahmadian, Afshin
    et al.
    KTH, Skolan för bioteknologi (BIO), Genteknologi.
    Ren, Z P
    Williams, Cecilia
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Pontén, F
    Odeberg, Jacob
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Pontén, J
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Lundeberg, Joakim
    KTH, Skolan för bioteknologi (BIO), Genteknologi.
    Genetic instability in the 9q22.3 region is a late event in the development of squamous cell carcinoma.1998Ingår i: Oncogene, ISSN 0950-9232, E-ISSN 1476-5594, Vol. 17, nr 14Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Squamous cell carcinoma (SCC) of the skin represents a group of neoplasms which is associated with exposure to UV light. Recently, we obtained data suggesting that invasive skin cancer and its precursors derive from one original neoplastic clone. Here, the analysis were extended by loss of heterozygosity (LOH) analysis in the chromosome 9q22.3 region. A total of 85 samples, taken from twenty-two sections of sun-exposed sites, corresponding to normal epidermis, morphological normal cells with positive immuno-staining for the p53 protein (p53 patches), dysplasias, cancer in situ (CIS) and squamous cell carcinomas (SCC) of the skin were analysed. Overall, about 70% of p53 patches had mutations in the p53 gene but not LOH in the p53 gene or 9q22.3 region. Approximately 70% of the dysplasias showed p53 mutations of which about 40% had LOH in the p53 region but not in the 9q22.3 region. In contrast, about 65% of SCC and CIS displayed LOH in the 9q22.3 region, as well as frequent (80%) mutations and/or LOH in the p53 gene. These findings strongly suggest that alterations in the p53 gene is an early event in the progression towards SCC, whereas malignant development involves LOH and alterations in at least one (or several) tumor suppressor genes located in chromosome 9q22.3.

  • 171.
    Ahmadian, Afshin
    et al.
    KTH, Tidigare Institutioner, Bioteknologi.
    Russom, Aman
    KTH, Tidigare Institutioner, Bioteknologi.
    Andersson, Helene
    KTH, Tidigare Institutioner, Bioteknologi.
    Uhlén, Mathias
    KTH, Tidigare Institutioner, Bioteknologi.
    Stemme, Göran
    KTH, Tidigare Institutioner, Bioteknologi.
    Nilsson, Peter
    KTH, Tidigare Institutioner, Bioteknologi.
    SNP analysis by allele-specific extension in a micromachined filter chamber2002Ingår i: BioTechniques, ISSN 0736-6205, E-ISSN 1940-9818, Vol. 32, nr 4, s. 748-754Artikel i tidskrift (Refereegranskat)
  • 172. Ahmed, A. Ahmed
    et al.
    El-Seedi, Hesham R.
    Mahmoud, Ahmed A.
    El-Douski, Abd El-Aziz A.
    Zeid, Ibrahim F.
    Bohlin, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Eudesmane derivatives from Laggera crispata and Pluchea carolonesis1998Ingår i: Phytochemistry, ISSN 0031-9422, E-ISSN 1873-3700, Vol. 49, nr 8, s. 2421-2424Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Investigation of the aerial parts of Laggera crispata and Pluchea carolonesis afforded in addition to several known compounds, three new eudesmane derivatives, 3β,4α-dihydroxy-7-epi-eudesm-11(13)-ene, 3α-(2′,3′-dihydroxy-2′-methylbutanoyl)-4,11-dihydroxy-6,7-dehydroeudesman-8-one and 3α-(3′-chloro-2′-hydroxy-2′-methylbutanoyl)cuauhtemone. The structures were elucidated by spectroscopic methods

  • 173. Ahmed, Aisha S.
    et al.
    Li, Jian
    Ahmed, Mahmood
    Hua, Long
    Yakovleva, Tatiana
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Ossipov, Michael H.
    Bakalkin, Georgy
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Stark, André
    Attenuation of Pain and Inflammation in Adjuvant-Induced Arthritis by the Proteasome Inhibitor MG1322010Ingår i: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 62, nr 7, s. 2160-2169Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective. In rheumatoid arthritis (RA), pain and joint destruction are initiated and propagated by the production of proinflammatory mediators. Synthesis of these mediators is regulated by the transcription factor NF-kappa B, which is controlled by the ubiquitin proteasome system (UPS). The present study explored the effects of the proteasome inhibitor MG132 on inflammation, pain, joint destruction, and expression of sensory neuropeptides as markers of neuronal response in a rat model of arthritis. Methods. Arthritis was induced in rats by injection of heat-killed Mycobacterium butyricum. Arthritis severity was scored, and nociception was evaluated by mechanical pressure applied to the hind paw. Joint destruction was assessed by radiologic and histologic analyses. NF-kappa B DNA-binding activity was analyzed by electromobility shift assay, and changes in the expression of the p50 NF-kappa B subunit and the proinflammatory neuropeptides substance P (SP) and calcitonin generelated peptide (CGRP) were detected by immunohistochemistry. Results. Arthritic rats treated with MG132 demonstrated a marked reduction in inflammation, pain, and joint destruction. The elevated DNA-binding activity of the NF-kappa B/p50 homodimer and p50, as well as the neuronal expression of SP and CGRP, observed in the ankle joints of arthritic rats were normalized after treatment with MG132. Conclusion. In arthritic rats, inhibition of proteasome reduced the severity of arthritis and reversed the pain behavior associated with joint inflammation. These effects may be mediated through the inhibition of NF-kappa B activation and may possibly involve the peripheral nervous system. New generations of nontoxic proteasome inhibitors may represent a novel pharmacotherapy for RA.

  • 174.
    Ahmed, Laeeq
    et al.
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsvetenskap och beräkningsteknik (CST).
    Edlund, Åke
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsvetenskap och beräkningsteknik (CST).
    Laure, Erwin
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsvetenskap och beräkningsteknik (CST).
    Whitmarsh, S.
    Parallel real time seizure detection in large EEG data2016Ingår i: IoTBD 2016 - Proceedings of the International Conference on Internet of Things and Big Data, SciTePress, 2016, s. 214-222Konferensbidrag (Refereegranskat)
    Abstract [en]

    Electroencephalography (EEG) is one of the main techniques for detecting and diagnosing epileptic seizures. Due to the large size of EEG data in long term clinical monitoring and the complex nature of epileptic seizures, seizure detection is both data-intensive and compute-intensive. Analysing EEG data for detecting seizures in real time has many applications, e.g., in automatic seizure detection or in allowing a timely alarm signal to be presented to the patient. In real time seizure detection, seizures have to be detected with negligible delay, thus requiring lightweight algorithms. MapReduce and its variations have been effectively used for data analysis in large dataset problems on general-purpose machines. In this study, we propose a parallel lightweight algorithm for epileptic seizure detection using Spark Streaming. Our algorithm not only classifies seizures in real time, it also learns an epileptic threshold in real time. We furthermore present "top-k amplitude measure" as a feature for classifying seizures in the EEG, that additionally assists in reducing data size. In a benchmark experiment we show that our algorithm can detect seizures in real time with low latency, while maintaining a good seizure detection rate. In short, our algorithm provides new possibilities in using private cloud infrastructures for real time epileptic seizure detection in EEG data.

  • 175.
    Ahmed, Meftun
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Oscillatory Ca2+ signaling in glucose-stimulated murine pancreatic β-cells: Modulation by amino acids, glucagon, caffeine and ryanodine2001Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Oscillations in cytoplasmic Ca2+ concentration ([Ca2+]i) is the key signal in glucose-stimulated β-cells governing pulsatile insulin release. The glucose response of mouse β-cells is often manifested as slow oscillations and rapid transients of [Ca2+] i. In the present study, microfluorometric technique was used to evaluate the role of amino acids, glucagon, ryanodine and caffeine on the generation and maintenance of [Ca2+] i oscillations and transients in individual murine β-cells and isolated mouse pancreatic islets. The amino acids glycine, alanine and arginine, at around their physiological concentrations, transformed the glucose-induced slow oscillations of [Ca2+] i in isolated mouse β-cells into sustained elevation. Increased Ca2+ entry promoted the reappearance of the slow [Ca2+] i oscillations. The [Ca2+] i oscillations were more resistant to amino acid transformation in intact islets, supporting the idea that cellular interactions are important for maintaining the oscillatory activity. Individual rat β-cells responded to glucose stimulation with slow [Ca2+] i oscillations due to periodic entry of Ca2+ as well as with transients evoked by mobilization of intracellular stores. The [Ca2+] i oscillations in rat β-cells had a slightly lower frequency than those in mouse β-cells and were more easily transformed into sustained elevation in the presence of glucagon or caffeine. The transients of [Ca2+] i were more common in rat than in mouse β-cells and often appeared in synchrony also in cells lacking physical contact. Depolarization enhanced the generation of [Ca2+] i transients. In accordance with the idea that β-cells have functionally active ryanodine receptors, it was found that ryanodine sometimes restored oscillatory activity abolished by caffeine. However, the IP3 receptors are the major Ca2+ release channels both in β-cells from rats and mice. Single β-cells from ob/ob mice did not differ from those of lean controls with regard to frequency, amplitudes and half-widths of the slow [Ca2+] i oscillations. Nevertheless, there was an excessive firing of [Ca2+] i transients in the β-cells from the ob/ob mice, which was suppressed by leptin at close to physiological concentrations. The enhanced firing of [Ca2+] i transients in ob/ob mouse β-cells may be due to the absence of leptin and mediated by activation of the phospholipase C signaling pathway.

  • 176.
    Ahmed Nazad, Zina
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Farmakologi.
    MicroRNAs as biomarkers in some cardiovascular diseases: A bioinformatics and review study2017Självständigt arbete på avancerad nivå (yrkesexamen), 20 poäng / 30 hpStudentuppsats (Examensarbete)
  • 177. Ahmed, Omar Jamil
    et al.
    McFarland, James
    Kumar, Arvind
    Brown University, United States.
    Reactivation in ventral striatum during hippocampal ripples: evidence for the binding of reward and spatial memories?2008Ingår i: Journal of Neuroscience, ISSN 0270-6474, E-ISSN 1529-2401, Vol. 28, nr 40, s. 9895-9897Artikel i tidskrift (Refereegranskat)
  • 178. Ahn, Jae Eun
    et al.
    Karlsson, Mats O.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Dunne, Adrian
    Ludden, Thomas M.
    Likelihood based approaches to handling data below the quantification limit using NONMEM VI2008Ingår i: Journal of Pharmacokinetics and Pharmacodynamics, ISSN 1567-567X, E-ISSN 1573-8744, Vol. 35, nr 4, s. 401-421Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    PURPOSE: To evaluate the likelihood-based methods for handling data below the quantification limit (BQL) using new features in NONMEM VI. METHODS: A two-compartment pharmacokinetic model with first-order absorption was chosen for investigation. Methods evaluated were: discarding BQL observations (M1), discarding BQL observations but adjusting the likelihood for the remaining data (M2), maximizing the likelihood for the data above the limit of quantification (LOQ) and treating BQL data as censored (M3), and like M3 but conditioning on the observation being greater than zero (M4). These four methods were compared using data simulated with a proportional error model. M2, M3, and M4 were also compared using data simulated from a positively truncated normal distribution. Successful terminations and bias and precision of parameter estimates were assessed. RESULTS: For the data simulated with a proportional error model, the overall performance was best for M3 followed by M2 and M1. M3 and M4 resulted in similar estimates in analyses without log transformation. For data simulated with the truncated normal distribution, M4 performed better than M3. CONCLUSIONS: Analyses that maximized the likelihood of the data above the LOQ and treated BQL data as censored provided the most accurate and precise parameter estimates.

  • 179.
    Ahnfelt, Emelie
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci.
    Al-Tikriti, Yassir
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci.
    Sjögren, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci.
    Lennernäs, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci.
    Hansson, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci.
    Single bead investigation of a clinical drug delivery system – a novel release mechanismManuskript (preprint) (Övrigt vetenskapligt)
  • 180.
    Ahnfelt, Emelie
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci.
    Degerstedt, Oliver
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci.
    Lilienberg, Elsa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci.
    Sjögren, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci.
    Hansson, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci.
    Lennernäs, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci.
    In vitro evaluation of lipiodol-based emulsions in clinical useManuskript (preprint) (Övrigt vetenskapligt)
  • 181.
    Ahnfelt, Emelie
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci.
    Sjögren, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci.
    Axén, N.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci.
    Lennernäs, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci.
    A miniaturized in vitro release method for investigating drug-release mechanisms2015Ingår i: International Journal of Pharmaceutics, ISSN 0378-5173, E-ISSN 1873-3476, Vol. 486, nr 1-2, s. 339-349Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We have evaluated a miniaturized in vitro method, based on the mDISS Profiler (TM) technique that enables on-line monitoring of drug release from a 21 mu l sample with 10 ml of release medium. Four model drugs in eight clinically used formulations, including both solid and non-solid drug delivery systems, were investigated. The acquired data were compared with historical in vitro release data from the same formulations. Use of the Weibull function to describe the in vitro drug-release profiles allowed discrimination between the selected formulations with respect to the drug-release mechanisms. Comparison of the release data from the same formulation in different in vitro set-ups showed that the methodology used can affect the mechanism of in vitro release. We also evaluated the ability of the in vitro methods to predict in vivo activity by comparing simulated plasma concentration-time profiles acquired from the application of the biopharmaceutical software GI-Sim to the in vitro observations. In summary, the simulations based on the miniaturized-method release data predicted the plasma profiles as well as or more accurately than simulations based on the historical release data in 71% of the cases and this miniaturized in vitro method appears to be applicable for both solid and non-solid formulations.

  • 182.
    Ahnfelt, Emelie
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci.
    Sjögren, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci.
    Hansson, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci.
    Lennernäs, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci.
    In Vitro Release Mechanisms of Doxorubicin From a Clinical Bead Drug-Delivery System2016Ingår i: Journal of Pharmaceutical Sciences, ISSN 0022-3549, E-ISSN 1520-6017, Vol. 105, nr 11, s. 3387-3398Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The release rate of doxorubicin (DOX) from the drug-delivery system (DDS), DC Bead, was studied by 2 miniaturized in vitro methods: free-flowing and sample reservoir. The dependencies of the release mechanisms on in vitro system conditions were investigated experimentally and by theoretical modeling. An inverse relationship was found between release rates and bead size, most likely due to the greater total surface area. The release rates correlated positively with temperature, release medium volume, and buffer strength, although the release medium volume had larger effect than the buffer strength. The sample reservoir method generated slower release rates, which described the in vivo release profile more accurately than the free-flowing method. There was no difference between a pH of 6.3 or 7.4 on the release rate, implying that the slightly acidic tumor microenvironment is less importance for drug release. A positive correlation between stirring rate and release rate for all DDS sizes was observed, which suggests film controlled release. Theoretical modeling highlighted the influence of local equilibrium of protonation, self-aggregation, and bead material interactions of DOX. The theoretical release model might describe the observed larger sensitivity of the release rate to the volume of the release medium compared to buffer strength. A combination of miniaturized in vitro methods and theoretical modeling are useful to identify the important parameters and processes for DOX release from a micro gel-based DDS.

  • 183.
    Ahnfelt, Nils-Otto
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten.
    Gas chromatographic analysis of amines, aminophenols and aminobutyric acids: studies on the derivatization with chloroformate esters1982Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
  • 184. Aho, Leena
    et al.
    Karkola, Kari
    Juusela, Jari
    Alafuzoff, Irina
    Department of Neuroscience and Neurology, University of Kuopio Finland .
    Heavy alcohol consumption and neuropathological lesions: a post-mortem human study2009Ingår i: Journal of Neuroscience Research, ISSN 0360-4012, E-ISSN 1097-4547, Vol. 87, nr 12, s. 2786-2792Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Epidemiological studies have indicated that excessive alcohol consumption leads to cognitive impairment, but the specific pathological mechanism involved remains unknown. The present study evaluated the association between heavy alcohol intake and the neuropathological hallmark lesions of the three most common neurodegenerative disorders, i.e., Alzheimer's disease (AD), dementia with Lewy bodies (DLB), and vascular cognitive impairment (VCI), in post-mortem human brains. The study cohort was sampled from the subjects who underwent a medicolegal autopsy during a 6-month period in 1999 and it included 54 heavy alcohol consumers and 54 age- and gender-matched control subjects. Immunohistochemical methodology was used to visualize the aggregation of beta-amyloid, hyperphosphorylated tau, and alpha-synuclein and the extent of infarcts. In the present study, no statistically significant influence was observed for alcohol consumption on the extent of neuropathological lesions encountered in the three most common degenerative disorders. Our results indicate that alcohol-related dementia differs from VCI, AD, and DLB; i.e., it has a different etiology and pathogenesis.

  • 185. Aho, Leena
    et al.
    Pikkarainen, Maria
    Hiltunen, Mikko
    Leinonen, Ville
    Alafuzoff, Irina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Immunohistochemical Visualization of Amyloid-β Protein Precursor and Amyloid-β in Extra- and Intracellular Compartments in the Human Brain2010Ingår i: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 20, nr 4, s. 1015-1028Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Amyloid-beta (Abeta) peptide, a cleavage product of the amyloid-beta protein precursor (AbetaPP), has been reported to be detected in the intracellular compartment. Most studies reporting the presence of intracellular Abeta are based on the use of immunohistochemistry. In this study, the presence of AbetaPP and Abeta was assessed by applying immunohistochemistry in postmortem human brain tissue samples obtained from 10 neurologically intact subjects, the youngest being 2 years of age, one aged with mild cognitive impairment, 14 neurologically diseased, and in one brain biopsy sample obtained from a subject with normal pressure hydrocephalus. Intracellular immunoreactivity was detected in all ages independent of the disease state or existence of extracellular Abeta aggregates with all antibodies directed to AbetaPP, with three Abeta antibodies (4G8, 6E10, and 82E1), clones that are unable to distinguish Abeta from AbetaPP. These results suggest that it is AbetaPP rather than Abeta that is detected intracellularly when using the antibodies listed above. Furthermore, the staining results varied when different pretreatment strategies were applied. Interestingly intracellular Abeta was detected with antibodies directed to the C-terminus of Abeta (neoepitope) in subjects with Alzheimer's disease. The lack of intracellular immunoreactivity in unimpaired subjects, when using antibodies against neoepitopes, may be due to a lack or a low level of the protein that is thus undetectable at light microscopic level by immunohistochemistry method. The staining results and conclusions depended strongly on the chosen antibody and the pretreatment strategy and thus multiple antibodies must be used when assessing the intracellular accumulation of Abeta.

  • 186.
    Aho, Nikolas
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Proczkowska-Björklund, Marie
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    Svedin, Carl Göran
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, Barn- och ungdomspsykiatriska kliniken.
    Victimization, polyvictimization , and health in Swedish adolescents2016Ingår i: Adolescent Health, Medicine and Therapeutics, ISSN 1179-318X, Vol. 7, s. 89-99Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The main objective of this article was to study the relationship between the different areas of victimization (eg, sexual victimization) and psychological symptoms, taking into account the full range of victimization domains. The final aim was to contribute further evidence regarding the bias that studies that focus on just one area of victimization may be introduced into our psychological knowledge. The sample included 5,960 second-year high school students in Sweden with a mean age of 17.3 years (range =16–20 years, standard deviation =0.652), of which 49.6% were females and 50.4% males. The Juvenile Victimization Questionnaire and the Trauma Symptom Checklist for Children were used to assess victimization and psychological problems separately. The results show that a majority of adolescents have been victimized, females reported more total events and more sexual victimization and childhood maltreatment, and males were more often victims of conventional crime. The majority of victimization domains as well as the sheer number of events (polyvictimization [PV]) proved to be harmful to adolescent health, affecting females more than males. PV explained part of the health effect and had an impact on its own and in relation to each domain. This suggests the possibility that PV to a large degree explains trauma symptoms. In order to understand the psychological effects of trauma, clinicians and researchers should take into account the whole range of possible types of victimization.

  • 187. Aho, Vilma
    et al.
    Ollila, Hanna M.
    Rantanen, Ville
    Kronholm, Erkki
    Surakka, Ida
    van Leeuwen, Wessel M. A.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Stressforskningsinstitutet. University of Helsinki, Finland; Finnish Institute of Occupational Health, Finland.
    Lehto, Maili
    Matikainen, Sampsa
    Ripatti, Samuli
    Härmä, Mikko
    Sallinen, Mikael
    Salomaa, Veikko
    Jauhiainen, Matti
    Alenius, Harri
    Paunio, Tiina
    Porkka-Heiskanen, Tarja
    Partial Sleep Restriction Activates Immune Response-Related Gene Expression Pathways: Experimental and Epidemiological Studies in Humans2013Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, nr 10, artikel-id e77184Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Epidemiological studies have shown that short or insufficient sleep is associated with increased risk for metabolic diseases and mortality. To elucidate mechanisms behind this connection, we aimed to identify genes and pathways affected by experimentally induced, partial sleep restriction and to verify their connection to insufficient sleep at population level. The experimental design simulated sleep restriction during a working week: sleep of healthy men (N = 9) was restricted to 4 h/night for five nights. The control subjects (N = 4) spent 8 h/night in bed. Leukocyte RNA expression was analyzed at baseline, after sleep restriction, and after recovery using whole genome microarrays complemented with pathway and transcription factor analysis. Expression levels of the ten most up-regulated and ten most down-regulated transcripts were correlated with subjective assessment of insufficient sleep in a population cohort (N = 472). Experimental sleep restriction altered the expression of 117 genes. Eight of the 25 most up-regulated transcripts were related to immune function. Accordingly, fifteen of the 25 most up-regulated Gene Ontology pathways were also related to immune function, including those for B cell activation, interleukin 8 production, and NF-kappa B signaling (P<0.005). Of the ten most up-regulated genes, expression of STX16 correlated negatively with self-reported insufficient sleep in a population sample, while three other genes showed tendency for positive correlation. Of the ten most down-regulated genes, TBX21 and LGR6 correlated negatively and TGFBR3 positively with insufficient sleep. Partial sleep restriction affects the regulation of signaling pathways related to the immune system. Some of these changes appear to be long-lasting and may at least partly explain how prolonged sleep restriction can contribute to inflammation-associated pathological states, such as cardiometabolic diseases.

  • 188. Ahrenstedt, Örjan
    et al.
    Knutson, L
    Nilsson, B
    Nilsson Ekdahl, Kristina
    University Hospital, Uppsala.
    Odlind, B
    Hällgren, R
    Enhanced local production of the complement components in the small intestine in Crohn's disease1990Ingår i: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 322, s. 1345-1349Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    There is evidence that complement components may be formed locally in inflammatory lesions containing monocytes and macrophages. To investigate the role of complement in Crohn's disease we measured jejunal-fluid concentrations of the complement components C4, C3, and factor B by perfusion of a closed segment of the jejunum in 22 patients with Crohn's disease thought to be limited to the terminal ileum.

    The mean (±SEM) jejunal-fluid C4 concentration was 2.0±0.3 mg per liter, significantly higher than the mean level in 35 healthy controls (0.7±0.1 mg per liter; P<0.001). The mean C3 concentration was 1.0±0.1 mg per liter in the patients and 0.7±0.1 mg per liter in the controls (P<0.05). The factor B levels were similar in the two groups. Calculated rates of intestinal secretion of these components showed differences of the same magnitude. Leakage of protein from plasma was not increased. The jejunal-fluid serum ratios of these complement proteins indicated that their appearance in the lumen of the jejunum was due at least in part to local mucosal synthesis. The increased jejunal secretion of C4, but not C3 or factor B, paralleled the clinical activity of Crohn's disease. Values were normal in first-degree relatives of the patients (n = 13), patients with celiac disease (n = 8), and patients with ulcerative colitis (n = 4).

    We conclude that increased secretion of complement by clinically unaffected jejunal tissue in patients with Crohn's disease reflects the systemic nature of this disorder and may be due to the stimulated synthesis of complement by activated intestinal monocytes and macrophages. 

  • 189.
    Ahrén, Anna
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Immunhistokemisk undersökning av paraffinbäddade celler från pleuravätska som kompletterande underlag för diagnos av cancermetastaser2005Självständigt arbete på grundnivå (kandidatexamen), 10 poäng / 15 hpStudentuppsats
    Abstract [en]

    Background. Immunohistochemistry is a useful method in the differential diagnosis between pleural mesotheliomas and metastatic adenocarcinomas in the pleura. Cytokeratin 20 and 7 have been used successfully as markers in studies determining primary location of adenocarcinomas from metastases. The current study is a complementary research of archived paraffininbedded material of cases with cancer origin. This study contributes a bigger statistical material that may facilitate the search for unknown primary site of adenocarcinoma by identification of metastatic cells in the pleura.

    Methods. Cells from the pleura taken from fifteen patients with diagnosed cancer of different types and eleven patients with cancer of unknown origin, were stained with antibodies against the tumour markers: Ber EP 4, calretinin, cytokeratin 20 and 7, estrogen receptor α, thyroid transcription factor, prostate-specific antigen and Cdx2.The staining was conducted in an automated immunohistochemical system. The staining of each kind of antibody was confirmed by a control section staining.

    Results. All control staining ended perfect The whole panel of antibodies used on mammary cancer showed the same pattern for every antibody. Of the patients with cancer of unknown origin there were four that gave the same pattern, two men and two women. The women are deceased. To make a more careful evaluation more information and clinic background is needed. The number of samples is too small to draw any statistical conclusions.

    Comment. Although the control staining was perfect the negative result of CK20 in the cases of diagnosed colon cancer was unexpected. This staining should be performed again to confirm the result. In some cases the number of cells were to few for a certain evaluation. The slides and the results of this work will be archived for further research.

  • 190.
    Aili, Daniel
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Sensorvetenskap och Molekylfysik. Linköpings universitet, Tekniska högskolan.
    Polypeptide-Based Nanoscale Materials2008Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Self-assembly has emerged as a promising technique for fabrication of novel hybrid materials and nanostructures. The work presented in this thesis has been focused on developing nanoscale materials based on synthetic de novo designed polypeptides. The polypeptides have been utilized for the assembly of gold nanoparticles, fibrous nanostructures, and for sensing applications.

    The 42-residue polypeptides are designed to fold into helix-loop-helix motifs and dimerize to form four-helix bundles. Folding is primarily driven by the formation of a hydrophobic core made up by the hydrophobic faces of the amphiphilic helices. The peptides have either a negative or positive net charge at neutral pH, depending on the relative abundance of Glu and Lys. Charge repulsion thus prevents homodimerization at pH 7 while promoting hetero-dimerization through the formation of stabilising salt bridges. A Cys incorporated in position 22, located in the loop region, allowed for directed, thiol-dependent, immobilization on planar gold surfaces and gold nanoparticles. The negatively charged (Glu-rich) peptide formed homodimers and folded in solution at pH < 6 or in the presence of certain metal ions, such as Zn2+. The folding properties of this peptide were retained when immobilized directly on gold, which enabled reversible assembly of gold nanoparticles resulting in aggregates with well-defined interparticle separations. Particle aggregation was found to induce folding of the immobilized peptides but folding could also be utilized to induce aggregation of the particles by exploiting the highly specific interactions involved in both homodimerization and hetero-association. The possibility to control the assembly of polypeptide-functionalized gold nanoparticles was utilized in a colorimetric protein assay. Analyte binding to immobilized ligands prevented the formation of dense particle aggregates when subjecting the particles to conditions normally causing extensive aggregation. Analyte binding could hence easily be distinguished by the naked eye. Moreover, the peptides were utilized to assemble gold nanoparticles on planar gold and silica substrates.

    Fibrous nanostructures were realized by linking monomers through a disulphide-bridge. The disulphide-linked peptides were found to spontaneously assemble into long and extremely thin peptide fibres as a result of a propagating association mediated by folding into four-helix bundles.

  • 191.
    Aili, Daniel
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Sensorvetenskap och Molekylfysik. Linköpings universitet, Tekniska högskolan.
    Enander, Karin
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Sensorvetenskap och Molekylfysik. Linköpings universitet, Tekniska högskolan.
    Rydberg, Johan
    Linköpings universitet, Institutionen för fysik, kemi och biologi. Linköpings universitet, Tekniska högskolan.
    Nesterenko, Irina
    Linköpings universitet, Institutionen för fysik, kemi och biologi. Linköpings universitet, Tekniska högskolan.
    Björefors, Fredrik
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Sensorvetenskap och Molekylfysik. Linköpings universitet, Tekniska högskolan.
    Baltzer, Lars
    Division of Organic Chemistry, Department of Biochemistry and Organic Chemistry, BMC, Box 599, Uppsala University, SE-751 24 Uppsala, Sweden..
    Liedberg, Bo
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Sensorvetenskap och Molekylfysik. Linköpings universitet, Tekniska högskolan.
    Controlled Assembly of Gold Nanoparticles using De Novo Designed Polypeptide Scaffolds2008Ingår i: Proceedings SPIE, Vol. 6885, Photonic Biosensing and Microoptics, 2008, s. 688506-1-688506-8Konferensbidrag (Refereegranskat)
    Abstract [en]

    Heterodimerization between designed helix-loop-helix polypeptides was utilized in order to assemble gold nanoparticles on planar substrates. The peptides were designed to fold into four-helix bundles upon dimerization. A Cys-residue in the loop region was used to immobilize one of the complementary peptides on a maleimide containing SAM on planar gold substrates whereas the second peptide was immobilized directly on gold nanoparticles. Introducing the peptide decorated particles over a peptide functionalized surface resulted in particle assembly. Further, citrate stabilized particles were assembled on amino-silane modified glass and silicon substrates. By subsequently introducing peptides and gold nanoparticles, particle-peptide hybrid multi layers could be formed.

  • 192.
    Aili, Daniel
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Sensorvetenskap och Molekylfysik. Linköpings universitet, Tekniska högskolan.
    Enander, Karin
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Sensorvetenskap och Molekylfysik. Linköpings universitet, Tekniska högskolan.
    Rydberg, Johan
    Linköpings universitet, Institutionen för fysik, kemi och biologi. Linköpings universitet, Tekniska högskolan.
    Nesterenko, Irina
    Linköpings universitet, Institutionen för fysik, kemi och biologi. Linköpings universitet, Tekniska högskolan.
    Björefors, Fredrik
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Sensorvetenskap och Molekylfysik. Linköpings universitet, Tekniska högskolan.
    Baltzer, Lars
    Department of Biochemistry and Organic Chemistry, BMC, Box 599, Uppsala UniVersity, SE-751 24 Uppsala, Sweden.
    Liedberg, Bo
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Sensorvetenskap och Molekylfysik. Linköpings universitet, Tekniska högskolan.
    Folding Induced Assembly of Polypeptide Decorated Gold Nanoparticles2008Ingår i: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 130, nr 17, s. 5780-5788Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Reversible assembly of gold nanoparticles controlled by the homodimerization and folding of an immobilized de novo designed synthetic polypeptide is described. In solution at neutral pH, the polypeptide folds into a helix–loop–helix four-helix bundle in the presence of zinc ions. When immobilized on gold nanoparticles, the addition of zinc ions induces dimerization and folding between peptide monomers located on separate particles, resulting in rapid particle aggregation. The particles can be completely redispersed by removal of the zinc ions from the peptide upon addition of EDTA. Calcium ions, which do not induce folding in solution, have no effect on the stability of the peptide decorated particles. The contribution from folding on particle assembly was further determined utilizing a reference peptide with the same primary sequence but containing both D and L amino acids. Particles functionalized with the reference peptide do not aggregate, as the peptides are unable to fold. The two peptides, linked to the nanoparticle surface via a cysteine residue located in the loop region, form submonolayers on planar gold with comparable properties regarding surface density, orientation, and ability to interact with zinc ions. These results demonstrate that nanoparticle assembly can be induced, controlled, and to some extent tuned, by exploiting specific molecular interactions involved in polypeptide folding.

  • 193.
    Aili, Daniel
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Sensorvetenskap och Molekylfysik. Linköpings universitet, Tekniska högskolan.
    Tai, Feng-I
    Linköpings universitet, Institutionen för fysik, kemi och biologi. Linköpings universitet, Tekniska högskolan.
    Enander, Karin
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Sensorvetenskap och Molekylfysik. Linköpings universitet, Tekniska högskolan.
    Baltzer, Lars
    Department of Biochemistry andOrganic Chemistry Uppsala University, BMC, Box 576, 75123 Uppsala, Sweden.
    Liedberg, Bo
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Sensorvetenskap och Molekylfysik. Linköpings universitet, Tekniska högskolan.
    Self-Assembly of Fibers and Nanorings from Disulfide-Linked Helix–Loop–Helix Polypeptides2008Ingår i: Angewandte Chemie International Edition, ISSN 1433-7851, E-ISSN 1521-3773, Vol. 47, nr 30, s. 5554-5556Artikel i tidskrift (Refereegranskat)
  • 194.
    Aili, Daniel
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Sensorvetenskap och Molekylfysik. Linköpings universitet, Tekniska högskolan.
    Enander, Karin
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Sensorvetenskap och Molekylfysik. Linköpings universitet, Tekniska högskolan.
    Rydberg, Johan
    Linköpings universitet, Institutionen för fysik, kemi och biologi. Linköpings universitet, Tekniska högskolan.
    Lundström, Ingemar
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Tillämpad Fysik. Linköpings universitet, Tekniska högskolan.
    Baltzer, Lars
    Linköpings universitet, Institutionen för fysik, kemi och biologi. Linköpings universitet, Tekniska högskolan.
    Liedberg, Bo
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Sensorvetenskap och Molekylfysik. Linköpings universitet, Tekniska högskolan.
    Aggregation-Induced Folding of a de novo Designed Polypeptide Immobilized on Gold Nanoparticles2006Ingår i: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 128, nr 7, s. 2194 -2195Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    This communication reports the first steps in the construction of a novel, nanoparticle-based hybrid material for biomimetic and biosensor applications. Gold nanoparticles were modified with synthetic polypeptides to enable control of the particle aggregation state in a switchable manner, and particle aggregation was, in turn, found to induce folding of the immobilized peptides.

  • 195.
    Aili, Margareta
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet).
    Isaksson, Elin L
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet).
    Carlsson, Sara E
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Wolf-Watz, Hans
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    Rosqvist, Roland
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet).
    Francis, Matthew S
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Regulation of Yersinia Yop-effector delivery by translocated YopE2008Ingår i: International Journal of Medical Microbiology, ISSN 1438-4221, E-ISSN 1618-0607, Vol. 298, nr 3-4, s. 183-192Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The bacterial pathogen Yersinia pseudotuberculosis uses a type III secretion (T3S) system to translocate Yop effectors into eukaryotic cells. Effectors are thought to gain access to the cytosol via pores formed in the host cell plasma membrane. Translocated YopE can modulate this pore formation through its GTPase-activating protein (GAP) activity. In this study, we analysed the role of translocated YopE and all the other known Yop effectors in the regulation of effector translocation. Elevated levels of Yop effector translocation into HeLa cells occurred by YopE-defective strains, but not those defective for other Yop effectors. Only Yersinia devoid of YopK exhibits a similar hyper-translocation phenotype. Since both yopK and yopE mutants also failed to down-regulate Yop synthesis in the presence of eukaryotic cells, these data imply that translocated YopE specifically regulates subsequent effector translocation by Yersinia through at least one mechanism that involves YopK. We suggest that the GAP activity of YopE might be working as an intra-cellular probe measuring the amount of protein translocated by Yersinia during infection. This may be a general feature of T3S-associated GAP proteins, since two homologues from Pseudomonas aeruginosa, exoenzyme S (ExoS) and exoenzyme T (ExoT), can complement the hyper-translocation phenotypes of the yopE GAP mutant.

  • 196.
    Ainegren, Mats
    Mittuniversitetet, Fakulteten för naturvetenskap, teknik och medier, Institutionen för teknik och hållbar utveckling.
    Roller skis' rolling resistance and grip characteristics: influences on physiological and performance measures in cross-country skiers2012Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [sv]

    Syftet med denna avhandling var att undersöka fristils- och klassiska rullskidors rullmotståndskoefficienter (μR) och klassiska rullskidors statiska friktionskoefficienter (μS) samt effekter av olika μR och μS på längdskidåkares prestation vid rullskidåkning på rullande band. Syftet var även att undersöka s.k. åkekonomi och mekanisk verkningsgrad mellan motionärer och kvinnliga och manliga junior- och seniorlängdskidåkare på elitnivå.Experimenten visade att under en period av 30 minuters kontinuerligt rullande, på rullande band, så sjönk μR signifikant (p<0.05) till 60-65 % och 70-75 % av initiala värden, för fristils- respektive klassiska rullskidor. Undersökandet av olika normalkrafter, hastigheter och lutningars påverkan på μR resulterade i en signifikant, negativ korrelation för μR som funktion av normalkraft, medan olika hastigheter och lutningar endast medförde små förändringar av μR.Studien som undersökte fysiologiska effekter av olika μR visade, vid submaximala konstanta arbetsbelastningar, att yttre effekt, syreupptagning, hjärtfrekvens och blodlaktat förändrades signifikant vid ~50 % förändring av μR. Försökspersonernas frekvens och sträcka per frekvens samt skattning av upplevd ansträngning resulterade dock i mestadels icke signifikanta eller små förändringar. Protokollen med successivt ökande arbetsbelastning (maxtest) resulterade i signifikant förändrad tid till utmattning, vid ~50 % förändring av μR. Detta inträffade utan signifikant skillnad i maximal syreupptagning, hjärtfrekvens och blodlaktat, vilket även mestadels gällde för skattning av upplevd ansträngning.Experimenten som undersökte klassiska rullskidors μS visade att dessa erhöll värden som är fem till åtta gånger högre än vad som rapporterats från studier av μS på snö med fästvallade skidor.Den efterföljande studien som undersökte fysiologiska och biomekaniska influenser av olika μS visade, vid submaximala konstanta arbetsbelastningar, att åkekonomin försämrades (~14 % högre syreförbrukning), hjärtfrekvensen ökade, den framåtdrivande kraften från benen på rullskidorna minskade samt att det blev kortare tid till utmattning (~30 %), vid maxtest, när skidåkarna använde rullskidor med en μS i likhet med vad som rapporterats för skidåkning på snö. För arbetsförsöken med olika rullskidor av olika fabrikat med en högre, och likartad, μS förelåg ingen skillnad i de undersökta variablerna.Studien som undersökte åkekonomi och mekanisk verkningsgrad som funktion av prestationsnivå, ålder och kön, visade att elitskidåkarna hade bättre åkekonomi och verkningsgrad (5-18 %) i jämförelse med motionärerna, att seniorerna hade bättre åkekonomi och verkningsgrad (4-5 %) än juniorerna och att ingen skillnad kunde konstateras mellan könen.

  • 197.
    Ainegren, Mats
    et al.
    Mittuniversitetet, Fakulteten för naturvetenskap, teknik och medier, Institutionen för teknik och hållbar utveckling.
    Ainegren, Mats
    Mittuniversitetet, Fakulteten för humanvetenskap, Institutionen för hälsovetenskap.
    Carlsson, Peter
    Mittuniversitetet, Fakulteten för naturvetenskap, teknik och medier, Institutionen för teknik och hållbar utveckling.
    Tinnsten, Mats
    Mittuniversitetet, Fakulteten för naturvetenskap, teknik och medier, Institutionen för teknik och hållbar utveckling.
    Roller ski rolling resistance and its effects on elite athletes’ performance2008Ingår i: ENGINEERING OF SPORT 7, VOL 2, 2008, Vol. 11, nr 3, s. 393-400Konferensbidrag (Refereegranskat)
    Abstract [en]

    Modern ski-treadmills allow cross-country skiers, biathletes and ski-orienteers to test their physical fitness in a laboratory environment whilst performing classical and freestyle (skating) techniques on roller skis. For elite athletes the differences in performance between test occasions are quite small, thus emphasising the importance of knowing the roller skis’ rolling resistance in order to allow the correct comparison between the results of different test occasions. In this study the roller skis’ rolling resistance has been measured using equipment on the ski-treadmill. The study investigates the influence of significant changes in rolling resistance on physiological variables. The results show that during submaximal exercise, heart rate, blood lactate, power and oxygen uptake are significantly changed by different rolling resistances, while there are no significant or only small changes to cycle rate, cycle length and ratings of perceived exertion. Incremental maximal tests show that time to exhaustion is significantly changed by different rolling resistances and this occurred without significant changes in maximal oxygen uptake and heart rate, and the influence on maximal power and ratings of perceived exertion were insignificant or small.

  • 198.
    Ainegren, Mats
    et al.
    Mittuniversitetet, Fakulteten för naturvetenskap, teknik och medier, Institutionen för teknik och hållbar utveckling.
    Ainegren, Mats
    Mittuniversitetet, Fakulteten för humanvetenskap, Institutionen för hälsovetenskap.
    Carlsson, Peter
    Mittuniversitetet, Fakulteten för naturvetenskap, teknik och medier, Institutionen för teknik och hållbar utveckling.
    Tinnsten, Mats
    Mittuniversitetet, Fakulteten för naturvetenskap, teknik och medier, Institutionen för teknik och hållbar utveckling.
    Roller ski rolling resistance and its effects on elite athletes’ performance2009Ingår i: Sports Engineering, ISSN 1369-7072, E-ISSN 1460-2687, Vol. 11, nr 3, s. 143-157Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Modern ski-treadmills allow cross-country skiers, biathletes and ski-orienteers to test their physical fitness in a laboratory environment whilst performing classical and freestyle (skating) techniques on roller skis. For elite athletes, the differences in performance between test occasions are quite small, thus emphasising the importance of knowing the roller skis’ rolling resistance in order to allow the correct comparison between the results of different test occasions. In this study, the roller skis’ rolling resistance was measured on the ski-treadmill’s surface using a roller ski rolling resistance measurement system specially produced for this purpose. The study investigated the influence of significant changes in rolling resistance on physiological variables. The results showed that during submaximal exercise, power, oxygen uptake, heart rate and blood lactate were significantly changed by different rolling resistances, while there were no significant or only small changes to cycle rate, cycle length and ratings of perceived exertion. Incremental maximal tests showed that time to exhaustion was significantly changed by different rolling resistances and this occurred without significant changes in maximal power, maximal oxygen uptake, maximal heart rate and blood lactate, and that the influence on ratings of perceived exertion were insignificant or small.

     

  • 199.
    Ainegren, Mats
    et al.
    Mittuniversitetet, Fakulteten för naturvetenskap, teknik och medier, Institutionen för teknik och hållbar utveckling.
    Ainegren, Mats
    Mittuniversitetet, Fakulteten för humanvetenskap, Institutionen för hälsovetenskap.
    Carlsson, Peter
    Mittuniversitetet, Fakulteten för naturvetenskap, teknik och medier, Institutionen för teknik och hållbar utveckling.
    Tinnsten, Mats
    Mittuniversitetet, Fakulteten för naturvetenskap, teknik och medier, Institutionen för teknik och hållbar utveckling.
    Rolling resistance for treadmill roller skiing2008Ingår i: Sports Engineering, ISSN 1369-7072, E-ISSN 1460-2687, Vol. 11, nr 1, s. 23-29Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Modern treadmills allow cross-country skiers, biathletes and ski-orienteers to test their physical performance under laboratory conditions using classical and freestyle techniques on roller skis. The differences in performance between tests are quite small for elite athletes, and it is therefore of great importance to control the rolling resistance of the roller skis. Otherwise different physiological tests cannot be accurately compared.

    This study shows that during a warm-up period of  30 minutes the coefficient of rolling resistance (µR) decreases to about 60-65% and 70-75% of its initial value for freestyle and classical roller skis respectively.

    Simultaneous measurements of temperature and µR shows that stabilized rolling resistance corresponds to a certain running temperature for a given normal force on the roller ski.

    Tests were also performed on the influence on µR of normal force, velocity and inclination. Normal forces produced significant influence on µR , while different velocities and inclinations of the treadmill only resulted in small changes in µR.

  • 200.
    Ainegren, Mats
    et al.
    Mittuniversitetet, Fakulteten för naturvetenskap, teknik och medier, Avdelningen för kvalitetsteknik, maskinteknik och matematik.
    Carlsson, Peter
    Mittuniversitetet, Fakulteten för naturvetenskap, teknik och medier, Avdelningen för kvalitetsteknik, maskinteknik och matematik.
    Laaksonen, Marko S.
    Mittuniversitetet, Fakulteten för humanvetenskap, Avdelningen för hälsovetenskap.
    Tinnsten, Mats
    Mittuniversitetet, Fakulteten för naturvetenskap, teknik och medier, Avdelningen för kvalitetsteknik, maskinteknik och matematik.
    The influence of grip on oxygen consumption and leg forces when using classical style roller skis2014Ingår i: Scandinavian Journal of Medicine and Science in Sports, ISSN 0905-7188, E-ISSN 1600-0838, Vol. 24, nr 2, s. 301-310Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The purpose of this study was to investigate the influence of classical style roller skis' grip (static friction coefficients, μ S) on cross-country skiers' oxygen consumption and leg forces during treadmill roller skiing, when using the diagonal stride and kick double poling techniques. The study used ratcheted wheel roller skis from the open market and a uniquely designed roller ski with an adjustable camber and grip function. The results showed significantly (P≤0.05) higher oxygen consumption (∼14%), heart rate (∼7%), and lower propulsive forces from the legs during submaximal exercise and a shorter time to exhaustion (∼30%) in incremental maximal tests when using roller skis with a μ S similar to on-snow skiing, while there was no difference between tests when using different pairs of roller skis with a similar, higher μ S. Thus, we concluded that oxygen consumption (skiing economy), propulsive leg forces, and performance time are highly changed for the worse when using roller skis with a lower μ S, such as for on-snow skiing with grip-waxed cross-country skis, in comparison to ratcheted wheel roller skis with several times higher μ S.

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