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  • 1.
    Ahonen, Linda
    et al.
    Steno Diabetes Center Copenhagen, Gentofte, Denmark.
    Jäntti, Sirkku
    Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.
    Suvitaival, Tommi
    Steno Diabetes Center Copenhagen, Gentofte, Denmark.
    Theilade, Simone
    Steno Diabetes Center Copenhagen, Gentofte, Denmark.
    Risz, Claudia
    Steno Diabetes Center Copenhagen, Gentofte, Denmark.
    Kostiainen, Risto
    Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.
    Rossing, Peter
    Steno Diabetes Center Copenhagen, Gentofte, Denmark; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
    Oresic, Matej
    Örebro University, School of Medical Sciences. Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, Finland.
    Hyötyläinen, Tuulia
    Örebro University, School of Science and Technology.
    Targeted Clinical Metabolite Profiling Platform for the Stratification of Diabetic Patients2019In: Metabolites, ISSN 2218-1989, E-ISSN 2218-1989, Vol. 9, no 9, article id E184Article in journal (Refereed)
    Abstract [en]

    Several small molecule biomarkers have been reported in the literature for prediction and diagnosis of (pre)diabetes, its co-morbidities, and complications. Here, we report the development and validation of a novel, quantitative method for the determination of a selected panel of 34 metabolite biomarkers from human plasma. We selected a panel of metabolites indicative of various clinically-relevant pathogenic stages of diabetes. We combined these candidate biomarkers into a single ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method and optimized it, prioritizing simplicity of sample preparation and time needed for analysis, enabling high-throughput analysis in clinical laboratory settings. We validated the method in terms of limits of detection (LOD) and quantitation (LOQ), linearity (R2), and intra- and inter-day repeatability of each metabolite. The method's performance was demonstrated in the analysis of selected samples from a diabetes cohort study. Metabolite levels were associated with clinical measurements and kidney complications in type 1 diabetes (T1D) patients. Specifically, both amino acids and amino acid-related analytes, as well as specific bile acids, were associated with macro-albuminuria. Additionally, specific bile acids were associated with glycemic control, anti-hypertensive medication, statin medication, and clinical lipid measurements. The developed analytical method is suitable for robust determination of selected plasma metabolites in the diabetes clinic.

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    Targeted Clinical Metabolite Profiling Platform for the Stratification of Diabetic Patients
  • 2.
    Almstedt, Elin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Neuro-Oncology.
    Rosén, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Neuro-Oncology.
    Gloger, Marleen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology.
    Rebecka, Stockard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Neuro-Oncology.
    Hekmati, Neda
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Neuro-Oncology.
    Koltowska, Katarzyna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology.
    Krona, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Neuro-Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Nelander, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Neuro-Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Real-time evaluation of glioblastoma growth in patient-specific zebrafish xenografts2021In: Neuro-Oncology, ISSN 1522-8517, E-ISSN 1523-5866, Vol. 24, no 5, p. 726-738Article in journal (Refereed)
    Abstract [en]

    Background: Patient-derived xenograft (PDX) models of glioblastoma (GBM) are a central tool for neuro-oncology research and drug development, enabling the detection of patient-specific differences in growth, and in vivo drug response. However, existing PDX models are not well suited for large-scale or automated studies. Thus, here, we investigate if a fast zebrafish-based PDX model, supported by longitudinal, AI-driven image analysis, can recapitulate key aspects of glioblastoma growth and enable case-comparative drug testing.

    Methods: We engrafted 11 GFP-tagged patient-derived GBM IDH wild-type cell cultures (PDCs) into 1-day-old zebrafish embryos, and monitored fish with 96-well live microscopy and convolutional neural network analysis. Using light-sheet imaging of whole embryos, we analyzed further the invasive growth of tumor cells.

    Results: Our pipeline enables automatic and robust longitudinal observation of tumor growth and survival of individual fish. The 11 PDCs expressed growth, invasion and survival heterogeneity, and tumor initiation correlated strongly with matched mouse PDX counterparts (Spearman R = 0.89, p < 0.001). Three PDCs showed a high degree of association between grafted tumor cells and host blood vessels, suggesting a perivascular invasion phenotype. In vivo evaluation of the drug marizomib, currently in clinical trials for GBM, showed an effect on fish survival corresponding to PDC in vitro and in vivo marizomib sensitivity.

    Conclusions: Zebrafish xenografts of GBM, monitored by AI methods in an automated process, present a scalable alternative to mouse xenograft models for the study of glioblastoma tumor initiation, growth, and invasion, applicable to patient-specific drug evaluation.

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  • 3. Alrifaiy, Ahmed
    et al.
    Borg, Johan
    Lindahl, Olof A.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Department of Computer Science, Electrical and Space Engineering, Luleå University of Technology; CMTF, Centre for Biomedical Engineering and Physics, Luleå and Umeå, Sweden; Department of Engineering Sciences and Mathematics, Luleå University of Technology.
    Ramser, Kerstin
    A lab-on-a-chip for hypoxic patch clamp measurements combined with optical tweezers and spectroscopy-first investigations of single biological cells2015In: Biomedical engineering online, E-ISSN 1475-925X, Vol. 14, article id 36Article in journal (Refereed)
    Abstract [en]

    The response and the reaction of the brain system to hypoxia is a vital research subject that requires special instrumentation. With this research subject in focus, a new multifunctional lab-on-a-chip (LOC) system with control over the oxygen content for studies on biological cells was developed. The chip was designed to incorporate the patch clamp technique, optical tweezers and absorption spectroscopy. The performance of the LOC was tested by a series of experiments. The oxygen content within the channels of the LOC was monitored by an oxygen sensor and verified by simultaneously studying the oxygenation state of chicken red blood cells (RBCs) with absorption spectra. The chicken RBCs were manipulated optically and steered in three dimensions towards a patch-clamp micropipette in a closed microfluidic channel. The oxygen level within the channels could be changed from a normoxic value of 18% O-2 to an anoxic value of 0.0-0.5% O-2. A time series of 3 experiments were performed, showing that the spectral transfer from the oxygenated to the deoxygenated state occurred after about 227 +/- 1 s and a fully developed deoxygenated spectrum was observed after 298 +/- 1 s, a mean value of 3 experiments. The tightness of the chamber to oxygen diffusion was verified by stopping the flow into the channel system while continuously recording absorption spectra showing an unchanged deoxygenated state during 5400 +/- 2 s. A transfer of the oxygenated absorption spectra was achieved after 426 +/- 1 s when exposing the cell to normoxic buffer. This showed the long time viability of the investigated cells. Successful patching and sealing were established on a trapped RBC and the whole-cell access (Ra) and membrane (Rm) resistances were measured to be 5.033 +/- 0.412 M Omega and 889.7 +/- 1.74 M Omega respectively.

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  • 4.
    Anderson, Fredrick
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    β3-adrenergic antagonism alleviates weight loss associated with cancer cachexia2017Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Cancer induced cachexia (CIC) is a devastating wasting disorder affecting people with tumor diseases and is deemed responsible for approximately 20% of all cancer-related deaths. This syndrome is associated with atrophy of adipose tissue and skeletal muscle. No established treatment is available for CIC and the underlying mechanisms are unveiled. However, one proposed culprit is brown adipose tissue (BAT) and browning of white adipose tissue (WAT), which produces heat via activation uncoupling protein 1 (UCP1). The result is increased energy wasting. Β3-adrenergic receptor (ADRB3) signaling activates BAT and we hypothesized that treatment with a specific ADRB3 antagonist would mitigate energy wasting in CIC. Balb/ca nude mice implanted with the LuCAP32 human xenograft tumor was used as a model system for CIC. The mice were treated with the selective ADRB3-blocker SR59230A and the unselective ADRB1 and 2-blocker propranolol for 4 weeks. A vehicle (VEH) and non-tumor bearing (NTB) group was also used. Significant effects were seen on total body weight loss with SR-treatment compared to VEH. Similar effects were seen on the wasting of local WAT depots. When measuring body composition, we found moderate evidence that SR spares the wasting of lean mass. We were also able to show decreased gene expression of BAT-markers, as well as markers for lipolysis, in the subcutaneous WAT. This supports our main hypothesis. In conclusion, we can show that treatment with a selective ADRB3 antagonist alleviates the symptoms of CIC through decreased lipolysis and decreased browning of WAT. These findings add to the mechanistic understanding of the pathophysiology of CIC and could be a potential treatment strategy for this syndrome.

  • 5.
    Andersson, Katrin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Approved medicinal products with potential companion diagnostic tests: An Inventory of the Swedish/European drug market2023Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    The newly introduced regulation (EU) 2017/746 aims to make In Vitro Diagnostic Medical Devices (IVDMD), which include companion diagnostic tests (CDx), a widespread method of authorising medicinal products in the European market. However, European SmPCs (Summary of Product Characteristics) currently do not explicitly refer to the term or classify tests associated with medicinal products as CDx. This paper is the first to examine and classify tests for medicinal products currently authorised in Sweden as being potential CDx, under the definitions of the new regulatory paradigm. The aim is to serve as the foundation for future research. 141 medicinal products with potential associated CDx are identified in the database of the Swedish Medical Products Agency (MPA). These products are then classified under the major ATC (Anatomical Therapeutic Chemical) therapeutic areas to search for commonalities and patterns in their usage and are later examined in conjunction with the techniques they use. The results reveal that a majority are concentrated in the Antineoplastic and immunomodulating agents and Antiinfectives for systemic use therapeutic areas. The methods used by these tests reveal diversity among the test technique usage, including instances where multiple techniques comprise a single CDx product, which may focus on detecting several biomarkers.

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    annotated-Andersson.Katrin_Essay_2.6%20rev_vt23.pdf
  • 6.
    Andersson, Sören
    et al.
    Örebro University, School of Medical Sciences. Folkhälsomyndigheten, Public Health Agency of Sweden.
    Strid, Åke
    Örebro University, School of Science and Technology.
    CHIMERIC MOMP ANTIGEN2015Patent (Other (popular science, discussion, etc.))
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    Patent
  • 7.
    Andersson, Sören
    et al.
    Örebro University, School of Medical Sciences. Folkhälsomyndigheten, Public Health Agency of Sweden.
    Strid, Åke
    Örebro University, School of Science and Technology.
    Chimeric MOMP antigen2014Patent (Other (popular science, discussion, etc.))
    Abstract [en]

    The present invention regards polypeptides capable of eliciting an immunological response that is protective against Chlamydia trachomatis. The polypeptide comprises a first amino acid sequence which has at least 90% homology with the amino acid sequence according to SEQ ID NO: 1 and a second amino acid sequence which has at least 90% homology with the amino acid sequence according to SEQ ID NO: 2. Furthermore, production of these polypeptides and pharmaceutical compositions comprising them are also provided.

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    Patent
  • 8.
    Arndt, Anton
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Laboratory for Biomechanics and Motor Control.
    The evolution of running shoes2012Conference paper (Other academic)
  • 9.
    Arndt, Anton
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Laboratory for Biomechanics and Motor Control.
    Lundgren, Paul
    Liu, Anmin
    Nester, Christopher
    Maiwald, Christian
    Jones, Richard
    Lundberg, Arne
    The effect of a midfoot cut in the outer sole of a shoe on intrinsic foot kinematics during walking.2013In: Footwear Science, ISSN 1942-4280, Vol. 5, no 1, p. 63-69Article in journal (Refereed)
    Abstract [en]

    Modifications in shoe outer soles are frequently made with the intention of altering biomechanics of the foot inside the shoe. These modifications are however, generally based upon intuition with little or no scientific data for support. The purpose of this study was to quantify changes in intrinsic foot segmental kinematics between walking in a neutral shoe and a shoe modified with a clear cut forming a break underneath the midfoot, approximating the Lisfrancs joint.

    Five healthy male subjects participated in the study. Intracortical pins were inserted under sterile conditions and local anaesthetic in nine different bones of the foot and shank. The subjects performed 10 walking trials in both a neutral, standard, flatsoled, flexible walking shoe and in the same shoe with an approximately 1 cm deep cut aligned with the subjects’ Lisfrancs joint. Material tests showed that the cut reduced midfoot shoe bending stiffness by 23% to 38% and torsional stiffness by 23% to 28%. A helical axis approach was applied for calculating the 3D rotations about relevant joints.

    Kinematic trajectories in the sagittal, frontal, and transverse planes were normalised to the stance phase for seven selected joints to compare rotation patterns when wearing the two shoe conditions. Although one out of 21 ranges of motion (ROM) showed a significant difference, there is strong reason to regard this as the result of a type 1 error. Apart from this no differences in ROM occurred between the shoe conditions.

    The low subject number reduced the statistical power of the results. However, the study indicated that outer sole modifications that may be assumed to have clear effects upon foot kinematics, do not necessarily do so.

  • 10.
    Asalya, Kamal K.
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Funktionella studier av cancervarianter hos DNA Polymeras epsilon2023Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 11.
    Aurell, Siri
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Utveckling av PCR-baserad bestämning av Fcγ-allotyper2021Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 12.
    Bass, Tarek
    KTH, School of Biotechnology (BIO), Protein Technology.
    Affibody molecules targeting HER3 for cancer therapy2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

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

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  • 13.
    Bass, Tarek
    KTH, School of Biotechnology (BIO), Protein Technology.
    Evaluating the therapeutic potential of a dimeric HER3-binding affibody construct in comparison with a monoclonal antibody, seribantumab.Manuscript (preprint) (Other academic)
    Abstract [en]

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

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  • 14. Bello, M. A.
    et al.
    Ruiz-León, Y.
    Sandoval-Sierra, J. V.
    Rezinciuc, Svetlana
    KTH, School of Biotechnology (BIO), Glycoscience.
    Diéguez-Uribeondo, J.
    Scanning electron microscopy (SEM) protocols for problematic plant, oomycete, and fungal samples2017In: Journal of Visualized Experiments, E-ISSN 1940-087X, Vol. 2017, no 120, article id e55031Article in journal (Refereed)
    Abstract [en]

    Common problems in the processing of biological samples for observations with the scanning electron microscope (SEM) include cell collapse, treatment of samples from wet microenvironments and cell destruction. Using young floral tissues, oomycete cysts, and fungi spores (Agaricalesas examples, specific protocols to process delicate samples are described here that overcome some of the main challenges in sample treatment for image capture under the SEM. Floral meristems fixed with FAA (Formalin-Acetic-Alcohol) and processed with the Critical Point Dryer (CPD) did not display collapsed cellular walls or distorted organs. These results are crucial for the reconstruction of floral development. A similar CPD-based treatment of samples from wet microenvironments, such as the glutaraldehyde-fixed oomycete cysts, is optimal to test the differential growth of diagnostic characteristics (e.g., the cyst spines) on different types of substrates. Destruction of nurse cells attached to fungi spores was avoided after rehydration, dehydration, and the CPD treatment, an important step for further functional studies of these cells. The protocols detailed here represent low-cost and rapid alternatives for the acquisition of good-quality images to reconstruct growth processes and to study diagnostic characteristics.

  • 15. Bengtsson, Erik
    et al.
    Nerjovaj, Pashtrik
    Wangefjord, Sakarias
    Nodin, Björn
    Eberhard, Jakob
    Uhlén, Mathias
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Borgquist, Signe
    Jirström, Karin
    HMG-CoA reductase expression in primary colorectal cancer correlates with favourable clinicopathological characteristics and an improved clinical outcome2014In: Diagnostic Pathology, E-ISSN 1746-1596, Vol. 9, no 1, p. 78-Article in journal (Refereed)
    Abstract [en]

    Background: An association between tumor-specific HMG-CoA reductase (HMGCR) expression and good prognosis has previously been demonstrated in breast and ovarian cancer. In this study, the expression, clinicopathological correlates and prognostic value of HMGCR expression in colorectal cancer was examined. Findings: Immunohistochemical expression of HMGCR was assessed in tissue microarrays with primary tumours from 557 incident cases of colorectal cancer in the Malmo Diet and Cancer Study. Pearson's Chi Square test was applied to explore the associations between HMGCR expression and clinicopathological factors and other investigative biomarkers. Kaplan Meier analysis and Cox proportional hazards modeling were used to assess the relationship between HMGCR expression and cancer-specific survival (CSS) according to negative vs positive HMGCR expression. A total number of 535 (96.0%) tumours were suitable for analysis, of which 61 (11.4%) were HMGCR negative. Positive cytoplasmic HMGCR expression was associated with distant metastasis-free disease at diagnosis (p = 0.002), lack of vascular invasion (p = 0.043), microsatellite-instability (p = 0.033), expression of cyclin D1 (p = <0.001) and p21 (p = <0.001). Positive HMGCR expression was significantly associated with a prolonged CSS in unadjusted Cox regression analysis in the entire cohort (HR = 1.79; 95% CI 1.20-2.66) and in Stage III-IV disease (HR = 1.71; 95% CI 1.09-2.68), but not after adjustment for established clinicopathological parameters. Conclusions: Findings from this prospective cohort study demonstrate that HMGCR is differentially expressed in colorectal cancer and that positive expression is associated with favourable tumour characteristics and a prolonged survival in unadjusted analysis. The utility of HMGCR as a predictor of response to neoadjuvant or adjuvant statin treatment in colorectal cancer merits further study. Virtual slides: The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2115647072103464.

  • 16.
    Bengtsson, Katarina
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Surface Physics and Chemistry. Linköping University, Faculty of Science & Engineering. LunaMicro AB, Linköping, Sweden.
    Christoffersson, Jonas
    Linköping University, Department of Physics, Chemistry and Biology, Biotechnology. Linköping University, Faculty of Science & Engineering.
    Mandenius, Carl-Fredrik
    Linköping University, Department of Physics, Chemistry and Biology, Biotechnology. Linköping University, Faculty of Science & Engineering.
    Robinson, Nathaniel D
    Linköping University, Department of Physics, Chemistry and Biology, Surface Physics and Chemistry. Linköping University, Faculty of Science & Engineering. LunaMicro AB, Linköping, Sweden.
    A clip-on electroosmotic pump for oscillating flow in microfluidic cell culture devices2018In: Microfluidics and Nanofluidics, ISSN 1613-4982, E-ISSN 1613-4990, Vol. 22, no 3, article id 27Article in journal (Refereed)
    Abstract [en]

    Recent advances in microfluidic devices put a high demand on small, robust and reliable pumps suitable for high-throughput applications. Here we demonstrate a compact, low-cost, directly attachable (clip-on) electroosmotic pump that couples with standard Luer connectors on a microfluidic device. The pump is easy to make and consists of a porous polycarbonate membrane and poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) electrodes. The soft electrode and membrane materials make it possible to incorporate the pump into a standard syringe filter holder, which in turn can be attached to commercial chips. The pump is less than half the size of the microscope slide used for many commercial lab-on-a-chip devices, meaning that these pumps can be used to control fluid flow in individual reactors in highly parallelized chemistry and biology experiments. Flow rates at various electric current and device dimensions are reported. We demonstrate the feasibility and safety of the pump for biological experiments by exposing endothelial cells to oscillating shear stress (up to 5 dyn/cm2) and by controlling the movement of both micro- and macroparticles, generating steady or oscillatory flow rates up to ± 400 μL/min.

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  • 17.
    Bernzen, Noel
    Halmstad University, School of Business, Engineering and Science.
    Noellator: Vinterrollator2016Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Idag är det en hög andel av äldre personer, främst kvinnor, som använder rollatorer. De blir allt fler med tiden, då genomsnittsåldern av befolkningen blir allt högre. För att öka livskvalitet för de äldre, är det rekommenderat att promenera utomhus så ofta som möjligt, exempelvis med hjälp av en rollator. Ett problem som uppstår är att ingen rollator är anpassad för användning under vintern. I detta examensarbete har ett rollator-koncept tagits fram, speciellt anpassat för ”fyra årstider”. Detta innebär att konceptet har allt som en vanligt rollator har men även tillbehör som är användarvänliga i vilket väder som helst, såväl vid snö- som isförhållanden. Det innebär en komplettering med specialdesignade tillbehör som är enkla att byta oberoende av väderslag. En årstidsoberoende rollator blir dyrare än en vanligt rollator, men samtidigt skapas ett hjälpmedel som gör det lättare för användaren att vara en del av samhället och förbättra sin hälsa, vilket faktiskt är såväl viktigt som aktuellt

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  • 18. Birgersson, Madeleine
    et al.
    Katona, Borbala
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Lindskog, Cecilia
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Cancer precision medicine.
    Pontén, Fredrik
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Cancer precision medicine.
    Williams, Cecilia
    Antibody Validation for Estrogen Receptor Beta2022In: Estrogen Receptors. Methods in Molecular Biology / [ed] Eyster, K.M, Springer Nature, 2022, p. 1-23Chapter in book (Refereed)
  • 19.
    Biswas, Tuser
    et al.
    University of Borås, Faculty of Textiles, Engineering and Business.
    Yu, Junchun
    University of Borås, Faculty of Textiles, Engineering and Business.
    Nierstrasz, Vincent
    University of Borås, Faculty of Textiles, Engineering and Business.
    Digital inkjet printing of antimicrobial lysozyme on pretreated polyester fabric2022Conference paper (Refereed)
    Abstract [en]

    Lysozyme was inkjet printed on two different polyester fabrics considering several challenges of printing enzymes on synthetic fabric surfaces. Wettability of both the fabrics were improved by alkaline pre-treatment resulting reduction in water contact angle to 60±2 from 95°±3 and to 80°±2 from 115°±2 for thinner and coarser fabric respectively. Activity of lysozyme in the prepared ink was 9240±34 units/ml and reduced to 5946±23 units/ml as of collected after jetting process (before printing on fabric). The formulated ink was effectively inkjet printed on alkali treated polyester fabric for antimicrobial applications. Retention of higher activity of the printed fabric requires further studies on enzyme-fibre binding mechanisms and understanding protein orientation on fabric surface after printing

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  • 20.
    Boström, Sara
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Tidsstrukturer i vanemässiga mönster i mänskligt beteende utvärderat med aktigrafi och dagböcker2021Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 21. Brazalez, Astrid Algaba
    et al.
    Manholm, Lars
    Johansson, Martin
    Quevedo-Teruel, Oscar
    Miao, Jingwei
    KTH, School of Electrical Engineering and Computer Science (EECS), Electrical Engineering, Electromagnetic Engineering.
    Investigation of a Ka-band Luneburg Lens Made of a Glide-Symmetric Holey Structure2017In: 2017 INTERNATIONAL SYMPOSIUM ON ANTENNAS AND PROPAGATION (ISAP 2017), IEEE , 2017Conference paper (Refereed)
    Abstract [en]

    A Ka-hand 2D flat-profiled Luneburg lens antenna implemented with a glide-symmetric holey structure is presented. The required refractive index for the lens design has been investigated via an analysis of the hole depth and the gap between the two metallic layers constituting the lens. The final unit cell is described and applied to create the complete metasurface Luneburg lens showing that a plane wave is obtained when feeding at an opposite arbitrary point with a discrete source.

  • 22.
    Brechmann, Nils A.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Industrial Biotechnology.
    Magnetic bead-based isolation of biological therapeutic modalities2022Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Biopharmaceutical modalities, such as monoclonal antibodies or the less established cell therapies, are nowadays very important for the treatment of severe or incurable diseases. The manufacturing of such modalities is complex and costly, including the downstream processing, which is highly essential to ensure the safety and quality of the product.

    Currently, monoclonal antibody downstream processes are heavily based on column chromatography, such as Protein A affinity capture, and highly depended on clarified liquid. This leads to a step intensive process, which is not only costly but also generates significant reduction of yield for every additional step. The cell clarification, in particular, for high cell density cultures can be insufficient and result in clogging of the following step due to remaining particles in the liquid. Alternatively, the clarification can lead to a higher contamination of product variants and process related impurities, such as antibody aggregations and Host Cell Proteins (HCPs). On the other hand, for large scale commercialization of allogenic cell therapy approaches based on human induced pluripotent stem cell (hiPSC) cell lines, efficient and reliable methods to ensure safety and quality of the cell product are needed. The presence of undifferentiated cells in a cell product derived from hiPSCs represent a risk of tumour and teratoma formation in the patient. The removal of undifferentiated cells in the cell therapy product is critical, and reliable and scalable methods are needed to support off-the-shelf production.

    The work in this thesis aimed to develop an alternative downstream operational step based on magnetic beads linked with Protein A or Protein G and a magnetic separator system suitable for the purification of monoclonal antibodies or cell therapy products. Efforts were made to develop an efficient monoclonal antibody capture step, based on magnetic bead separation, directly applied on the harvest of monoclonal antibodies producing Chinese Hamster Ovary (CHO) cell cultures at different cell densities up to very high cell density (> 100 x 106 cells/mL) and scales ranging from small-scale to pilot-scale (up to 16 L). The system proved to be highly gentle towards the cell, minimizing aggregation and the release of HCPs (< 10 ppm) already complying with the regulatory constraint after only one downstream operational step. Furthermore, the magnetic bead-based separation was applied for the negative isolation of cell subpopulations based on unique surface marker expression. Here a flexible isolation system was developed based on Protein A or based on Protein G magnetic beads providing high variability towards the surface receptor recognizing antibody. The magnetic beads were substantially larger compared to a cell resulting in a binding process where a bead is being covered by several cells. The system was evaluated towards different surface receptors, i.e. HER2, TRA2-49 and SSEA-4. The magnetic beads showed to be non-toxic towards the delicate human mesenchymal stem cells and iPSCs. The system also provided excellent negative selection of HER2+ SKBR3 cells, taken as model, and TRA2- 49+/SSEA-4+ iPSCs from different heterogenous model cell populations.

    In conclusion, the present downstream strategies based on magnetic bead separation for the capture of monoclonal antibodies or for the negative selection of cell subpopulations showed great alternatives to resolve the challenges provided by intensified cultures in mAb manufacturing, and could provide a viable solution for cell therapy.

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  • 23. Carlsson, J
    et al.
    Gedda, L
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
    Grönvik, C
    Hartman, T
    Lindström, A
    Lindström, P
    Lundqvist, H
    Lövqvist, A
    Malmqvist, J
    Olsson, P
    Strategy for boron neutron capture therapy against tumor cells with over-expression of the epidermal growth factor-receptor.1994In: International Journal of Radiation Oncology, Biology, Physics, ISSN 0360-3016, E-ISSN 1879-355X, Vol. 30, no 1, p. 105-15Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Gliomas, squamous carcinomas and different adenocarcinomas from breast, colon and prostate might have an increased number of epidermal growth factor (EGF) receptors. The receptors are, in these cases, candidates for binding of receptor specific toxic conjugates that might inactivate cellular proliferation. The purpose of this study was to evaluate whether it is reasonable to try ligand-dextran based conjugates for therapy.

    METHODS AND MATERIALS: EGF or TGF alpha were conjugated to dextran and binding, internalization, retention and degradation of eight types of such conjugates were analyzed in EGF-receptor amplified glioma cells. The conjugates were labelled with radioactive nuclides to allow detection and two of the conjugates were carrying boron in the form of carboranyl amino acids or aminoalkyl-carboranes. Comparative binding tests, applying 125I-EGF, were made with cultured breast, colon and prostate adenocarcinoma, glioma and squamous carcinoma cells. Some introductory tests to label with 76Br for positron emission tomography and with 131I for radionuclide therapy were also made.

    RESULTS: The dextran part of the conjugates did not prevent receptor specific binding. The amount of receptor specific binding varied between the different types of conjugates and between the tested cell types. The dextran part improved intracellular retention and radioactive nuclides were retained for at least 20-24 h. The therapeutical effect improved when 131I was attached to EGF-dextran instead of native EGF.

    CONCLUSION: The improved cellular retention of the ligand-dextran conjugates is an important property since it gives extended exposure time when radionuclides are applied and flexibility in the choice of time for application of neutrons in boron neutron capture therapy (BNCT). It is possible that ligand-dextran mediated BNCT might allow, if the applied neutron fields covers rather wide areas around the primary tumor, locally spread cells that otherwise would escape treatment to be inactivated.

  • 24.
    Cedersund, G
    Linköping University, Department of Electrical Engineering. Linköping University, The Institute of Technology.
    Elimination of the initial value parameters when identifying a system close to a Hopf bifurcation.2006In: IEE Proceedings - Systems Biology, ISSN 1741-2471, E-ISSN 1741-248X, Vol. 153, no 6, p. 448-456Article in journal (Refereed)
    Abstract [en]

    One of the biggest problems when performing system identification of biological systems is that it is seldom possible to measure more than a small fraction of the total number of variables. If that is the case, the initial state, from where the simulation should start, has to be estimated along with the kinetic parameters appearing in the rate expressions. This is often done by introducing extra parameters, describing the initial state, and one way to eliminate them is by starting in a steady state. We report a generalisation of this approach to all systems starting on the centre manifold, close to a Hopf bifurcation. There exist biochemical systems where such data have already been collected, for example, of glycolysis in yeast. The initial value parameters are solved for in an optimisation sub-problem, for each step in the estimation of the other parameters. For systems starting in stationary oscillations, the sub-problem is solved in a straight-forward manner, without integration of the differential equations, and without the problem of local minima. This is possible because of a combination of a centre manifold and normal form reduction, which reveals the special structure of the Hopf bifurcation. The advantage of the method is demonstrated on the Brusselator.

  • 25.
    Cheddad, Abbas
    et al.
    Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).
    Nord, Christoffer
    Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).
    Hörnblad, Andreas
    Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).
    Prunskaite-Hyyryläinen, Renata
    Oulu Center for Cell-Matrix Research, Biocenter Oulu, Laboratory of Developmental Biology and Department of Medical Biochemistry and Molecular Biology, Institute of Biomedicine, University of Oulu, Finland.
    Eriksson, Maria
    Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).
    Georgsson, Fredrik
    Umeå University, Faculty of Science and Technology, Department of Computing Science.
    Vainio, Seppo
    Oulu Center for Cell-Matrix Research, Biocenter Oulu, Laboratory of Developmental Biology and Department of Medical Biochemistry and Molecular Biology, Institute of Biomedicine, University of Oulu, Finland.
    Ahlgren, Ulf
    Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).
    Improving signal detection in emission optical projection tomography via single source multi-exposure image fusion2013In: Optics Express, E-ISSN 1094-4087, Vol. 21, no 14, p. 16584-16604Article in journal (Refereed)
    Abstract [en]

    We demonstrate a technique to improve structural data obtained from Optical Projection Tomography (OPT) using Image Fusion (IF) and contrast normalization. This enables the visualization of molecular expression patterns in biological specimens with highly variable contrast values. In the approach, termed IF-OPT, different exposures are fused by assigning weighted contrasts to each. When applied to projection images from mouse organs and digital phantoms our results demonstrate the capability of IF-OPT to reveal high and low signal intensity details in challenging specimens. We further provide measurements to highlight the benefits of the new algorithm in comparison to other similar methods.

  • 26. Chen, Ye
    et al.
    Wang, Aiguo
    Ding, Huitong
    Que, Xia
    Li, Yabo
    An, Ning
    Jiang, Lili
    Umeå University, Faculty of Science and Technology, Department of Computing Science.
    A global learning with local preservation method for microarray data imputation2016In: Computers in Biology and Medicine, ISSN 0010-4825, E-ISSN 1879-0534, Vol. 77, p. 76-89Article in journal (Refereed)
    Abstract [en]

    Microarray data suffer from missing values for various reasons, including insufficient resolution, image noise, and experimental errors. Because missing values can hinder downstream analysis steps that require complete data as input, it is crucial to be able to estimate the missing values. In this study, we propose a Global Learning with Local Preservation method (GL2P) for imputation of missing values in microarray data. GL2P consists of two components: a local similarity measurement module and a global weighted imputation module. The former uses a local structure preservation scheme to exploit as much information as possible from the observable data, and the latter is responsible for estimating the missing values of a target gene by considering all of its neighbors rather than a subset of them. Furthermore, GL2P imputes the missing values in ascending order according to the rate of missing data for each target gene to fully utilize previously estimated values. To validate the proposed method, we conducted extensive experiments on six benchmarked microarray datasets. We compared GL2P with eight state-of-the-art imputation methods in terms of four performance metrics. The experimental results indicate that GL2P outperforms its competitors in terms of imputation accuracy and better preserves the structure of differentially expressed genes. In addition, GL2P is less sensitive to the number of neighbors than other local learning-based imputation. methods.

  • 27.
    Chovan, Jorik
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Ett nytt molekylärt verktyg för identifiering av funktionella cellgrupper baserat på nervcellsaktivitet, ljusstimulering och farmakologisk behandling in vivo2021Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 28.
    Chudinova, Ekaterina
    et al.
    Tomsk Polytechnic University, Tomsk, Russia.
    Surmeneva, Maria
    Tomsk Polytechnic University, Tomsk, Russia.
    Koptyug, Andrey
    Mid Sweden University, Faculty of Science, Technology and Media, Department of Quality Technology and Management, Mechanical Engineering and Mathematics.
    Skoglund, Per
    Mid Sweden University, Faculty of Science, Technology and Media, Department of Quality Technology and Management, Mechanical Engineering and Mathematics.
    Sharanova, A
    Tomsk Polytechnic University, Tomsk, Russia.
    Loza, K
    University of Duisburg-Essen, Germany.
    Epple, M
    University of Duisburg-Essen, Germany.
    Surmenev, Roman
    Tomsk Polytechnic University, Tomsk, Russia.
    Hydroxyapatite coating and silver nanoparticles assemblies on additively manufactured Ti6Al4V scaffolds2015Conference paper (Other academic)
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  • 29. Czub, Joanna
    et al.
    Banaś, Dariusz
    Braziewicz, Janusz
    Buraczewska, Iwona
    Jaskóła, Marian
    Kaźmierczak, Urszula
    Korman, Andrzej
    Lankoff, Anna
    Lisowska, Halina
    Szefliński, Zygmunt
    Wojewódzka, Maria
    Wójcik, Andrzej
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. Jan Kochanowski University, Poland.
    Biological effects of mixed-ion beams. Part 1: Effect of irradiation of the CHO-K1 cells with a mixed-ion beam containing the carbon and oxygen ions2018In: Applied Radiation and Isotopes, ISSN 0969-8043, E-ISSN 1872-9800, Vol. 139, p. 304-309Article in journal (Refereed)
    Abstract [en]

    Carbon and oxygen ions were accelerated simultaneously to estimate the effect of irradiation of living cells with the two different ions. This mixed ion beam was used to irradiate the CHO-K1 cells, and a survival test was performed. The type of the effect of the mixed ion beam on the cells was determined with the isobologram method, whereby survival curves for irradiations with individual ion beams were also used. An additive effect of irradiation with the two ions was found.

  • 30. Czub, Joanna
    et al.
    Banaś, Dariusz
    Braziewicz, Janusz
    Buraczewska, Iwona
    Jaskóła, Marian
    Kaźmierczak, Urszula
    Korman, Andrzej
    Lankoff, Anna
    Lisowska, Halina
    Szefliński, Zygmunt
    Wojewódzka, Maria
    Wójcik, Andrzej
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. Jan Kochanowski University, Poland.
    Biological effects of mixed-ion beams. Part 2: The relative biological effectiveness of CHO-K1 cells irradiated by mixed- and single-ion beams2019In: Applied Radiation and Isotopes, ISSN 0969-8043, E-ISSN 1872-9800, Vol. 150, p. 192-198Article in journal (Refereed)
    Abstract [en]

    The relative biological effectiveness (RBE) values were determined for single- and mixed-ion beams containing carbon and oxygen ions. The CHO-K1 cells were irradiated with beams with the linear energy transfer (LET) values of 236-300 and 461-470 keV/mu m for C-12 and O-16 ions, respectively. The RBE was estimated as a function of dose, survival fraction (SF) and LET. The SF was not affected by varying contributions of the constituent ions to the total mixed dose. The RBE has the same value for single-ion exposures with ions with LET 300 (C-12) and 470 keV/mu m (O-16).

  • 31.
    Dahlsson Leitao, Charles
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science.
    Affibody-mediated targeting of HER-family receptors for cancer imaging and therapy2022Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Proteins are remarkable molecules with diverse and specialized functions playing essential roles in most biological processes. One such function is protecting us from diseases by the action of antibodies in our immune system that can recognize and mediate the destruction of invading pathogens by binding to foreign epitopes found on non-self proteins. The concept of utilizing specific protein-protein interactions to achieve a therapeutic effect has for several decades been a cornerstone for the development of cancer-directed treatments. While antibodies have formed a basis for the development of such drugs, other protein alternatives may be engineered to complement current antibody-based treatments, and may even prove to possess superior features. 

     

    This thesis focuses on the engineering of affibody molecules, a small alternative scaffold protein, for design and development of novel cancer-targeting therapeutic and diagnostic drugs. There are many different strategies that have been investigated for inhibiting cancer progression and tumour growth with perhaps one of the most straightforward involving disruption of dysregulated growth-promoting signalling pathways. Members of the human epidermal growth factor receptor (HER) family is prominently expressed in various cancer types and have been shown to be intricately involved in tumorigenesis. One of the members (HER3) often becomes upregulated in cancer and have been shown to mediate acquired resistance to targeted therapies by the mechanism of ligand-induced activation. We have designed five novel affibody-based HER3-targeting molecules able to prevent ligand-binding and consequently activation of HER3. We investigated the targeting properties and biodistribution profiles of these molecules in vivo and subsequently evaluated the anti-tumour efficacy for the most promising variants in direct comparison to a HER3-targeting antibody with a similar inhibitory mechanism. We observed a large influence of design on both the biodistribution properties and the in vivo efficacy of different affibody molecules. Moreover, we demonstrated that two of the affibody-formats were equally effective as the antibody in inhibiting tumour growth and prolonging survival of mice bearing HER3-positive xenografts. The effectiveness of cancer treatments depends on efficient diagnostic approaches that can reliably stratify patients based on these targetable biomarkers, which is possible using radionuclide molecular imaging. We have performed a direct comparison of the diagnostic potential for visualizing HER3-expressing tumours of affibody- and antibody-based imaging probes. We concluded that affibody molecules provide superior imaging quality with higher diagnostic potential and enable early visualization of HER3-expression in tumours. 

     

    Another member of the HER family that is of interest for cancer therapy is HER1 (or EGFR) but due to substantial expression in healthy tissues, targeted therapies may lead to severe side-effects. One possible solution to this is taking advantage of the distinct milieu of the tumour microenvironment to design EGFR-targeting drugs that become conditionally activated at the tumour site, but not in normal tissues, with the aim of drastically reducing systemic toxicity. We have generated an affibody molecule with anti-idiotypic binding specificity for a previously generated EGFR-binding affibody molecule, which we used to construct an affibody-based prodrug. We were able to show that, in a proof-of-concept format, this anti-idiotypic masking domain was able to block the binding to EGFR until removed by protease-mediated cleavage. We subsequently developed and characterized a more refined version of this prodrug, which we call a pro-affibody, and could show that activation by cancer-associated proteases confers binding to EGFR-expressing cancer cells and enables conditional cytotoxic payload delivery in vitro. The pro-affibody was further evaluated in vivo using tumour-bearing mice to investigate the feasibility for masked uptake in healthy tissues while retaining binding-activity in tumours. We observed a substantial reduction in EGFR-specific liver uptake compared to a control construct without a masking domain, and a strong indication of protease-mediated EGFR-binding in tumours. 

     

    In conclusion, the experimental work presented in this thesis provides a rationale for designing effective affibody-based cancer therapeutics and diagnostics with different targeting strategies and demonstrates the potential of such drugs from preclinical in vivo data.  

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  • 32.
    Danø, Sune
    et al.
    Copenhagen University.
    Madsen, Mads F
    Copenhagen University.
    Schmidt, Henning
    Chalmers Technical University.
    Cedersund, Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
    Reduction of a biochemical model with preservation of its basic dynamic properties.2006In: The FEBS Journal, ISSN 1742-464X, E-ISSN 1742-4658, Vol. 273, no 21, p. 4862-4877Article in journal (Refereed)
    Abstract [en]

    The complexity of full-scale metabolic models is a major obstacle for their effective use in computational systems biology. The aim of model reduction is to circumvent this problem by eliminating parts of a model that are unimportant for the properties of interest. The choice of reduction method is influenced both by the type of model complexity and by the objective of the reduction; therefore, no single method is superior in all cases. In this study we present a comparative study of two different methods applied to a 20D model of yeast glycolytic oscillations. Our objective is to obtain biochemically meaningful reduced models, which reproduce the dynamic properties of the 20D model. The first method uses lumping and subsequent constrained parameter optimization. The second method is a novel approach that eliminates variables not essential for the dynamics. The applications of the two methods result in models of eight (lumping), six (elimination) and three (lumping followed by elimination) dimensions. All models have similar dynamic properties and pin-point the same interactions as being crucial for generation of the oscillations. The advantage of the novel method is that it is algorithmic, and does not require input in the form of biochemical knowledge. The lumping approach, however, is better at preserving biochemical properties, as we show through extensive analyses of the models.

  • 33.
    Du, Ning
    et al.
    Institute of Sports and Health, Beijing Sport University, China: Department of Orthopaedics, Fourth Medical Centre of Chinese PLA General Hospital, China.
    Yu, Ji-Guo
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Section of Sports Medicine.
    Song, YaFeng
    Institute of Sports and Health, Beijing Sport University, China.
    A brief review of the development of telerehabilitation and its application in patients of adolescent idiopathic scoliosis2023In: Journal of Scientific & Technical Research, ISSN 2574-1241, Vol. 48, no 2, article id 007634Article, review/survey (Refereed)
    Abstract [en]

    Adolescent idiopathic scoliosis (AIS) is a three-dimensional spinal deformity and characterized by progressive development during growth, and eventually to a curvature of the spine greater than 10 degrees on the posteroanterior radiograph. AIS usually does not present symptoms in early age, which makes the diagnosis and treatment of these patients difficult. Thus, a follow-up observation of all suspicious AIS patients becomes very important to monitor the progression of spinal cord deformity. Telerehabilitation is a new type of rehabilitation, which links the professional physiotherapists and the patients through telecommunication and information technology. Telerehabilitation can be synchronous (through any device real-time connection between patients and therapists), asynchronous (computer-based intervention for remote monitoring by the physiotherapists and offline adjustments), or a combination of both. The COVID-19 pandemic has caused medical health care system chaos and affected seriously the ongoing disease management in many countries. Telerehabilitation can reduce the spreading risk of COVID-19, the cost of face-to-face rehabilitation service, the pressure on the staff, and the financial burden on the patients. In this review, we briefly describe the development of telerehabilitation, its current status and related technologies, and its application in clinical practice of AIS. In addition, we discussed the limitations of the current telerehabilitation and its future prospection. We believe that telerehabilitation could provide high quality rehabilitation service to the patients, thus becoming the mainstream of rehabilitation to the population of AIS.

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  • 34.
    Dunn, Catriona
    et al.
    Leeds Teaching Hosp NHS Trust, England; Univ Leeds, England.
    Brettle, David
    Leeds Teaching Hosp NHS Trust, England.
    Cockroft, Martin
    Futamura Chem UK Ltd, England.
    Keating, Elizabeth
    Futamura Chem UK Ltd, England.
    Revie, Craig
    FFEI Ltd, England.
    Treanor, Darren
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical pathology. Linköping University, Center for Medical Image Science and Visualization (CMIV). Leeds Teaching Hosp NHS Trust, England; Univ Leeds, England; Leeds Teaching Hosp NHS Trust, England.
    Quantitative assessment of H&E staining for pathology: development and clinical evaluation of a novel system2024In: Diagnostic Pathology, E-ISSN 1746-1596, Vol. 19, no 1, article id 42Article in journal (Refereed)
    Abstract [en]

    BackgroundStaining tissue samples to visualise cellular detail and tissue structure is at the core of pathology diagnosis, but variations in staining can result in significantly different appearances of the tissue sample. While the human visual system is adept at compensating for stain variation, with the growth of digital imaging in pathology, the impact of this variation can be more profound. Despite the ubiquity of haematoxylin and eosin staining in clinical practice worldwide, objective quantification is not yet available. We propose a method for quantitative haematoxylin and eosin stain assessment to facilitate quality assurance of histopathology staining, enabling truly quantitative quality control and improved standardisation.MethodsThe stain quantification method comprises conventional microscope slides with a stain-responsive biopolymer film affixed to one side, called stain assessment slides. The stain assessment slides were characterised with haematoxylin and eosin, and implemented in one clinical laboratory to quantify variation levels.ResultsStain assessment slide stain uptake increased linearly with duration of haematoxylin and eosin staining (r = 0.99), and demonstrated linearly comparable staining to samples of human liver tissue (r values 0.98-0.99). Laboratory implementation of this technique quantified intra- and inter-instrument variation of staining instruments at one point in time and across a five-day period.ConclusionThe proposed method has been shown to reliably quantify stain uptake, providing an effective laboratory quality control method for stain variation. This is especially important for whole slide imaging and the future development of artificial intelligence in digital pathology.

  • 35.
    Ebai, Tonge
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular tools.
    Kamali-Moghaddam, Masood
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular tools.
    Landegren, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular tools.
    Parallel protein detection by solid-phase proximity ligation assay with real-time PCR or sequencing2015In: Current Protocol in Molecular Biology, ISSN 1934-3647, Vol. 109, no 20Article in journal (Refereed)
    Abstract [en]

    Proximity ligation assays are a group of protein detection techniques in which reagents with affinity for target proteins, typically antibodies, are coupled to short strands of DNA. DNA-modified affinity reagents are combined in assays constructed such that the coordinated binding of individual target molecules or complexes of interacting proteins by two or more of the reagents, followed by DNA ligation and/or polymerization reactions, gives rise to amplifiable DNA reporter strands. Proximity ligation assays have been shown to exhibit excellent sensitivity in single and multiplexed protein assays for individual or interacting proteins, both in solution and in situ. This unit describes procedures for developing solid-phase proximity ligation assays for soluble proteins using either real-time PCR or DNA sequencing as the readout. In addition, critical steps for assay optimization are discussed.

  • 36.
    Edstedt, Morgan
    Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).
    Jämförande histologiska och immunohistokemiska analyser av metabol levercancer i musmodeller2021Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 37. Enroth, Stefan
    et al.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Grankvist, Kjell
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Gyllensten, Ulf
    Effects of Long-Term Storage Time and Original Sampling Month on Biobank Plasma Protein Concentrations2016In: EBioMedicine, E-ISSN 2352-3964, Vol. 12, p. 309-314Article in journal (Refereed)
    Abstract [en]

    The quality of clinical biobank samples is crucial to their value for life sciences research. A number of factors related to the collection and storage of samples may affect the biomolecular composition. We have studied the effect of long-time freezer storage, chronological age at sampling, season and month of the year and on the abundance levels of 108 proteins in 380 plasma samples collected from 106 Swedish women. Storage time affected 18 proteins and explained 4.8–34.9% of the observed variance. Chronological age at sample collection after adjustment for storage-time affected 70 proteins and explained 1.1–33.5% of the variance. Seasonal variation had an effect on 15 proteins and month (number of sun hours) affected 36 proteins and explained up to 4.5% of the variance after adjustment for storage-time and age. The results show that freezer storage time and collection date (month and season) exerted similar effect sizes as age on the protein abundance levels. This implies that information on the sample handling history, in particular storage time, should be regarded as equally prominent covariates as age or gender and need to be included in epidemiological studies involving protein levels.

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  • 38.
    Eriksson, Emma
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Moreno, R
    Milenova, I. Yoanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Liljenfeldt, L
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Dieterich, L C
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Christiansson, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Karlsson, H
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Ullenhag, Gustav
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Mangsbo, Sara M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Dimberg, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Alemany, R
    Loskog, Angelica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Activation of myeloid and endothelial cells by CD40L gene therapy supports T-cell expansion and migration into the tumor microenvironment2017In: Gene Therapy, ISSN 0969-7128, E-ISSN 1476-5462, Vol. 24, no 2, p. 92-103Article in journal (Refereed)
    Abstract [en]

    CD40 is an interesting target in cancer immunotherapy due to its ability to stimulate T-helper 1 immunity via maturation of dendritic cells and to drive M2 to M1 macrophage differentiation. Pancreatic cancer has a high M2 content that has shown responsive to anti-CD40 agonist therapy and CD40 may thus be a suitable target for immune activation in these patients. In this study, a novel oncolytic adenovirus armed with a trimerized membrane-bound extracellular CD40L (TMZ-CD40L) was evaluated as a treatment of pancreatic cancer. Further, the CD40L mechanisms of action were elucidated in cancer models. The results demonstrated that the virus transferring TMZ-CD40L had oncolytic capacity in pancreatic cancer cells and could control tumor progression. TMZ-CD40L was a potent stimulator of human myeloid cells and T-cell responses. Further, CD40L-mediated stimulation increased tumor-infiltrating T cells in vivo, which may be due to a direct activation of endothelial cells to upregulate receptors for lymphocyte attachment and transmigration. In conclusion, CD40L-mediated gene therapy is an interesting concept for the treatment of tumors with high levels of M2 macrophages, such as pancreatic cancer, and an oncolytic virus as carrier of CD40L may further boost tumor killing and immune activation.

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  • 39.
    Forman, Olof
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Enskild vesikel analys av Caveolae-associerade proteiner2020Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 40.
    Frölander, Ida
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Mekanismer för långvarig allopregnanolon-medierad potentiering av GABAA-receptorer2020Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 41.
    Gao, Xiang
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Yang, Ting
    Liu, Ming
    Peleli, Maria
    Zollbrecht, Christa
    Weitzberg, Eddie
    Lundberg, Jon O.
    Persson, A. Erik G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Carlstrom, Mattias
    NADPH Oxidase in the Renal Microvasculature Is a Primary Target for Blood Pressure-Lowering Effects by Inorganic Nitrate and Nitrite2015In: Hypertension, ISSN 0194-911X, E-ISSN 1524-4563, Vol. 65, no 1, p. 161-+Article in journal (Refereed)
    Abstract [en]

    Renal oxidative stress and nitric oxide (NO) deficiency are key events in hypertension. Stimulation of a nitrate-nitrite-NO pathway with dietary nitrate reduces blood pressure, but the mechanisms or target organ are not clear. We investigated the hypothesis that inorganic nitrate and nitrite attenuate reactivity of renal microcirculation and blood pressure responses to angiotensin II (ANG II) by modulating nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity and NO bioavailability. Nitrite in the physiological range (10(-7)-10(-5) mol/L) dilated isolated perfused renal afferent arterioles, which were associated with increased NO. Contractions to ANG II (34%) and simultaneous NO synthase inhibition (56%) were attenuated by nitrite (18% and 26%). In a model of oxidative stress (superoxide dismutase-1 knockouts), abnormal ANG II-mediated arteriolar contractions (90%) were normalized by nitrite (44%). Mechanistically, effects of nitrite were abolished by NO scavenger and xanthine oxidase inhibitor, but only partially attenuated by inhibiting soluble guanylyl cyclase. Inhibition of NADPH oxidase with apocynin attenuated ANG II-induced contractility (35%) similar to that of nitrite. In the presence of nitrite, no further effect of apocynin was observed, suggesting NADPH oxidase as a possible target. In preglomerular vascular smooth muscle cells and kidney cortex, nitrite reduced both basal and ANG II-induced NADPH oxidase activity. These effects of nitrite were also abolished by xanthine oxidase inhibition. Moreover, supplementation with dietary nitrate (10(-2) mol/L) reduced renal NADPH oxidase activity and attenuated ANG II-mediated arteriolar contractions and hypertension (99+/-2-146+/-2 mm Hg) compared with placebo (100+/-3-168+/-3 mm Hg). In conclusion, these novel findings position NADPH oxidase in the renal microvasculature as a prime target for blood pressure-lowering effects of inorganic nitrate and nitrite.

  • 42.
    Glas, Peter
    et al.
    Swedish School of Sport and Health Sciences, GIH.
    Mattsson, C. Mikael
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences.
    Physiological requirements of elite handball – measured with a combination of local positioning system and heart rate monitoring.2017Conference paper (Refereed)
    Abstract [en]

    For all athletes, it is important to adjust training plans and competition schedule according to each individual's specific traits and situation. This is crucial in team sports, where players, despite being involved in the same sport, and even on the same team, may have very different physiological capacities and, also have completed a wide variety of work in both training and match situations. A first step towards being able to carry out individualized training is to accurately measure the amount of stress (physiological burden) for each individual. The purpose of the study was to create a comprehensive picture of the physical requirements of elite handball matches, and further investigate how the relationship between work load and physical capacity impacts performance.

    Heart rate measurements have since decades been used to quantify the relative work, and GPS measurement as a tool for objective values has been available for outdoor sports for about ten years, but GPS is not possible to use indoors. We have used a new technology with a similar system for indoor use called Local Positioning System (LPS) (Kinexon Precision Technologies, Münich, Germany) to record and analyze the players’ motion during games, and we have combined that technology with data from accelerometry, gyroscope and heart rate measurements.

    So far, 42 handball matches have been measured and analyzed, ranging from juniors (9 games U21 men's national team) to seniors, men and women, and both in Sweden’s highest league and between national teams (Women: 8 national and 7 international games; Men: 14 national and 4 international games).

    A first "result" is that the categorization of motion patterns need to be adapted to each sport. For example, some moves that should be counted as accelerations in handball are not recognized by the system, simply because it has been adapted to the pattern of motion on the much larger soccer field. This is similarly important to realize when comparing results for handball’s physiological requirements reached using other technologies. In this presentation, we will in part discuss the future technological opportunities, and in part report descriptive results, including how fast and far the players move, as well as differences between men and women, between national and international games, and between juniors and seniors.

  • 43.
    Gustafsson, Ida
    Umeå University, Faculty of Medicine, Department of Medical and Translational Biology.
    Hur påverkar ändringar i membrans fosfolipidasymmetri presenilinkomplexets aktivitet?2023Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 44.
    Gustafsson, Moa
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Förändringar i mukuslager och mikrobiota under utveckling av kolit hos Interleukin-10 negativa möss2023Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 45.
    Hadrevi, Jenny
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Sports medicine.
    Turkina, Maria V
    Department of Clinical and Experimental Medicine, Linköpings universitet.
    Carlsson, Anders
    Division of Community Medicine, Department of Medical and Health Sciences, Linköpings universitet.
    Gerdle, Björn
    Division of Community Medicine, Department of Medical and Health Sciences, Linköpings universitet.
    Larsson, Britt
    Division of Community Medicine, Department of Medical and Health Sciences, Linköpings universitet.
    Hellström, Fredrik
    Department of Occupational and Public Health Sciences, Högskolan i Gävle.
    Ghafouri, Bijar
    Division of Community Medicine, Department of Medical and Health Sciences, Linköpings universitet.
    Myosin light chain and calcium regulating protein differences in chronic musculoskeletal neck and shoulder pain2016In: Journal of Integrated Omnics, ISSN 2182-0287, Vol. 6, no 1, p. 1-8Article in journal (Refereed)
    Abstract [en]

    Proteomic screening analysis has detected myosin light chain (MLC) as a protein implied to be involved in chronic musculoskeletal neck and shoulder pain. Several analyses of MLC proteins have stated a difference in phosphorylation being the determining factor for protein activation hence altered contrability of the muscle in i.e. senescence. In continuation of a previous publication, this study is an attempt to analyze the different MLC isoforms by mass spectrometry and immune-analyses in myalgic and healthy trapezius muscle. In the present study no differences in phosphorylation level between the corresponding individual proteins were detected using LC-MSMS and immunoblotting; instead we assigned different isoforms of regulatory MLCs. To further elucidate the contrability: calcium (Ca2+) regulatory proteins, sarco(endo)plasmic reticulum Ca2+ ATPase 1 (SERCA-1) and calsequestrine (CSQ) were analyzed by western blot. The analysis revealed a significantly increased abundance of SERCA-1 protein in the myalgic muscle and a significantly increased abundance of CSQ in healthy muscle. Myalgic muscle contraction patterns have in previous studies shown to differ from healthy muscle which may be connected to the Ca2+ availability in the muscle. Here we present the proteomic characterization of differences in Ca2+ regulating proteins and particularly regulatory MLCs in trapezius muscle of women with chronic musculoskeletal neck and shoulder pain.

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  • 46.
    Hageberg, Ingvild U.
    et al.
    Norwegian Univ Sci & Technol, Norway.
    Arja, Katrianne
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Vindstad, Benedikte E.
    Norwegian Univ Sci & Technol, Norway.
    Bergvoll, Johannes K.
    Norwegian Univ Sci & Technol, Norway.
    Gederaas, Odrun A.
    Univ Agder, Norway.
    Melo, Thor-Bernt
    Norwegian Univ Sci & Technol, Norway.
    Nilsson, Peter
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Lindgren, Mikael
    Norwegian Univ Sci & Technol, Norway.
    Photophysics of Glycosylated Ring-Fused Chlorin Complexes and Their Photosensitizing Effects on Cancer Cells2023In: ChemPhotoChem, E-ISSN 2367-0932, Vol. 7, no 8, article id e202300028Article in journal (Refereed)
    Abstract [en]

    The future of photodynamic therapy (PDT) as a promising cancer treatment relies on the development of new selective and effective photosensitizers (PS) with improved photophysical and biochemical qualities. Herein, we present the synthetic procedure, photophysical properties and photosensitizing effects of novel glycosylated 4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine] fused chlorin agents featuring either glucose, galactose, or N-acetyl glucosamine. It is shown that both the proto- and Zn2+-ion forms of the ring-stabilized glycochlorins exhibit the required photophysical properties in terms of triplet excited states and singlet oxygen generation, the latter more than 50 % in organic solvents such as CHCl3. Employing the rat AY-27 and human T24 cancer cell models, it was found that these are superior to the corresponding unglycosylated chlorin in biological activity, and moreover, the proto form is 2-3 times superior to the Zn-stabilized variant. Provisional flow cytometry and cell localization studies of the proto-form indicate both necrotic and apoptotic biological activity, and that the photosensitizer localizes in the mitochondria, cell membrane and lysosomes. However, the localization into the lysosomes is dominating and increases substantially with time. We anticipate the findings will aid in the development of photosensitizers for targeted cancer PDT.

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  • 47.
    Hammond, Maria
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular tools.
    Kamali-Moghaddam, Masood
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular tools.
    Landegren, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular tools.
    A DNA-mediated search for optimal combinations of protein bindersManuscript (preprint) (Other academic)
  • 48.
    Hasmats, Johanna
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Analysis of genetic variations in cancer2012Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The aim of this thesis is to apply recently developed technologies for genomic variation analyses, and to ensure quality of the generated information for use in preclinical cancer research.

    Faster access to a patients’ full genomic sequence for a lower cost makes it possible for end users such as clinicians and physicians to gain a more complete understanding of the disease status of a patient and adjust treatment accordingly. Correct biological interpretation is important in this context, and can only be provided through fast and simple access to relevant high quality data.

    Therefore, we here propose and validate new bioinformatic strategies for biomarker selection for prediction of response to cancer therapy. We initially explored the use of bioinformatic tools to select interesting targets for toxicity in carboplatin and paclitaxel on a smaller scale. From our findings we then further extended the analysis to the entire exome to look for biomarkers as targets for adverse effects from carboplatin and gemcitabine. To investigate any bias introduced by the methods used for targeting the exome, we analyzed the mutation profiles in cancer patients by comparing whole genome amplified DNA to unamplified DNA. In addition, we applied RNA-seq to the same patients to further validate the variations obtained by sequencing of DNA. The understanding of the human cancer genome is growing rapidly, thanks to methodological development of analysis tools. The next step is to implement these tools as a part of a chain from diagnosis of patients to genomic research to personalized treatment.

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    Johanna Hasmats thesis
  • 49.
    Hellström, Fredrik
    et al.
    University of Gävle, Faculty of Health and Occupational Studies, Department of Occupational and Public Health Sciences, Occupational health science. University of Gävle, Centre for Musculoskeletal Research.
    Gouveia-Figueira, Sandra
    Department of Chemistry, Umeå University, Umeå; Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå.
    Nording, Malin
    Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå.
    Björklund, Martin
    University of Gävle, Faculty of Health and Occupational Studies, Department of Occupational and Public Health Sciences, Occupational health science. University of Gävle, Centre for Musculoskeletal Research. Department of Community Medicine and Rehabilitation, Umeå University, Umeå.
    Fowler, Christopher John
    Department of Community Medicine and Rehabilitation, Umeå universitet, Umeå.
    Association between plasma concentrations of linoleic acid-derived oxylipins and the perceived pain scores in an exploratory study in women with chronic neck pain2016In: BMC Musculoskeletal Disorders, E-ISSN 1471-2474, Vol. 17, no 1, article id 103Article in journal (Refereed)
    Abstract [en]

    Background: Chronic musculoskeletal pain may be associated with changes in the balance of algogenic and anti-nociceptive compounds, and that such changes may be visible in plasma samples. We have undertaken an exploratory study to measure the levels of endocannabinoids, related N-acylethanolamines and oxylipins (primarily those derived from linoleic acid) in plasma samples from women with chronic neck pain (NP) and chronic widespread pain (CWP), and to investigate whether the observed levels are associated with the pain experienced by these women.

    Methods: Blood samples from 35 women with NP, 15 with CWP and 27 age-matched controls were analysed for the lipids using an ultra performance liquid chromatography coupled to tandem mass spectrometry method. Current pain ("NRSday") and the average pain during the last week ("NRSweek") were rated by the participants using a numerical rating scale.

    Results: There were no significant differences in the plasma concentrations of the fifteen lipids investigated between the pain subjects and the controls. However, significant correlations were seen for the NP group between the NRSday scores and the plasma concentrations of the linoleic acid derivatives 9- and 13- hydroxy-10E,12Zoctadecadienoic acid (Spearman's rho values 0.51 [P=0.0016]) and 0.53 [P=0.0011], respectively).

    Conclusions: The data obtained in this exploratory study are consistent with a model whereby the underlying inflammatory nature of the musculoskeletal disorders leads both to an increase in the NRSday scores and the hydroxy-10E,12Z-octadecadienoic acid levels, and these increases further influence the perceived pain of in the NP subjects.

  • 50.
    Hernandez, Frank J
    Biodonostia Research Institute, San Sebastian, Spain.
    Hernandez, Luiza I.
    Biodonostia Research Institute, San Sebastian, Spain.
    Ozalp, Veli C.
    Istanbul Kemerburgaz University, School of Medicine, Istanbul, Turkey.
    Nanocapsules in biomedicine: promises and challenges2015In: Advanced Theranostics Materials / [ed] Ashutosh Tiwari et al, John Wiley & Sons, 2015Chapter in book (Other academic)
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