| 1. |
- Steding-Ehrenborg, Katarina, et al.
(author)
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Hydraulic force is a novel mechanism of diastolic function which may contribute to decreased diastolic filling in HFpEF and facilitate filling in HFrEF
- 2021
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In: Journal of Applied Physiology. - : American Physiological Society. - 1522-1601 .- 8750-7587. ; 130:4, s. 993-1000
-
Journal article (peer-reviewed)abstract
- BACKGROUND: A hydraulic force generated by blood moving the atrio-ventricular plane is a novel mechanism of diastolic function. The direction and magnitude of the force is dependent on the geometrical relationship between the left atrium and ventricle and is measured as the short-axis atrio-ventricular area difference (AVAD). In short, the net hydraulic force acts from a larger area towards a smaller. It is currently unknown how cardiac remodeling affects this mechanism. The aim of the study was therefore to investigate this diastolic mechanism in patients with pathological or physiological remodeling.METHODS: 70 subjects (n=11 heart failure with preserved ejection fraction (HFpEF), n=10 heart failure with reduced ejection fraction (HFrEF), n=7 signs of isolated diastolic dysfunction, n=10 hypertrophic cardiomyopathy (HCM), n=10 cardiac amyloidosis, n=18 triathletes and n=14 controls) were included. Subjects underwent Cardiac MR and short-axis images of the left atrium and ventricle were delineated. AVAD was calculated as ventricular area minus atrial area and used as an indicator of net hydraulic force.RESULTS: At the onset of diastole, AVAD in HFpEF was median -9.2 cm2 versus -4.4 cm2 in controls, p=0.02). The net hydraulic force was directed towards the ventricle for both, but larger in HFpEF. HFrEF was the only group with a positive median value 11.6 cm2 and net hydraulic force was throughout diastole directed towards the atrium.CONCLUSION: The net hydraulic force may impede cardiac filling throughout diastole in HFpEF, worsening diastolic dysfunction. In contrast, it may work favorably in patients with dilated ventricles and aid ventricular filling.
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| 2. |
- Afifi, Raafat, et al.
(author)
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SPE and HPLC monitoring of 17-β-estradiol in Egyptian aquatic ecosysetms
- 2016
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In: Journal of Liquid Chromatography and Related Technologies. - : Informa UK Limited. - 1082-6076 .- 1520-572X. ; 39:8, s. 428-434
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Journal article (peer-reviewed)abstract
- Solid-phase extraction and HPLC methods are described for monitoring of 17-β-estradiol residues in Egyptian aquatic ecosystems (water, fish, mollusks, sediment, and drinking water) at the Nile River, Suez Canal region, and northeast of Egypt. Molecular imprinted polymer was prepared and used in extraction. High performance liquid chromatography (HPLC) columns used were Supelcosil C18 and Nucleosil C18. The mobile phases used were different combinations of water and acetonitrile. The concentration of 17-β-estradiol in water, aquatic animals, and sediment samples were of 265.13–7988.12 µg/L, 0.503–96.167, and 0.775–11.884 µg/kg, respectively. Marine lake was contained with high levels of 17-β-estradiol (P < 0.05). Similarly, the Nile River downstream showed high levels of 17-β-estradiol. The detected concentrations in mollusks were significantly higher than those detected in fish. Tilapia fish did not show 17-β-estradiol. Contrarily, low concentrations were detected in the rivulet streams supplied by the Nile River. Besides, 17-β-estradiol was also detected in the sediments at low levels. Detection of 17-β-estradiol in the Egyptian ecosystems attracted attention toward heavy reliance on some esterogenic medicinal products in Egypt. The monitoring of 17-β-estradiol in other water bodies was recommended. Besides, the development of methodologies of bioremediation to eliminate 17-β-estradiol from the Egyptian and other water resources of the world was also suggested.
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| 3. |
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| 4. |
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| 5. |
- Ander, Malin, et al.
(author)
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Development of health-related quality of life and symptoms of anxiety and depression among persons diagnosed with cancer during adolescence : a 10-year follow-up study
- 2016
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In: Psycho-Oncology. - : Wiley. - 1057-9249 .- 1099-1611. ; 25:5, s. 582-589
-
Journal article (peer-reviewed)abstract
- Objective: The main aim was to investigate the development of health-related quality of life (HRQOL) and symptoms of anxiety and depression in a cohort diagnosed with cancer during adolescence from shortly after up to 10 years after diagnosis.Methods: Participants (n = 61) completed the SF-36 and the HADS shortly; six, 12, and 18 months; and two, three, four, and 10 years (n = 28) after diagnosis. Polynomial change trajectories were used to model development.Results: Polynomial change trajectories showed an initial increase which abated over time into a decrease which abated over time for the SF-36 subscales Mental Health and Vitality; an initial decline which abated over time into an increase for HADS anxiety; and an initial decline which abated over time into an increase which abated over time for HADS depression. The SF-36 mental component summary showed no change from two to 10 years after diagnosis whereas the SF-36 physical component summary showed an increase from two years after diagnosis which declined over time. Ten years after diagnosis 29% reported possible anxiety.Conclusions: Development of HRQOL and symptoms of anxiety and depression appears to be nonlinear among persons diagnosed with cancer during adolescence. Well into permanent survivorship an increase in symptoms of anxiety is shown and approximately a third of the participants report possible anxiety. The findings indicate the need for: studies designed to pinpoint the times of highest psychological risk, clinical follow-up focusing on psychological problems, and development of effective psychological interventions for survivors of adolescent cancer
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| 6. |
- Andersen, Karsten Brandt, et al.
(author)
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Stability of diphenylalanine peptide nanotubes in solution
- 2011
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In: Nanoscale. - : Royal Society of Chemistry (RSC). - 2040-3372 .- 2040-3364. ; 3:3, s. 994-998
-
Journal article (peer-reviewed)abstract
- Over the last couple of years, self-organizing nanotubes based on the dipeptide diphenylalanine have received much attention, mainly as possible building blocks for the next generation of biosensors and as drug delivery systems. One of the main reasons for this large interest is that these peptide nanotubes are believed to be very stable both thermally and chemically. Previously, the chemical and thermal stability of self-organizing structures has been investigated after the evaporation of the solvent. However, it was recently discovered that the stability of the structures differed significantly when the tubes were in solution. It has been shown that, in solution, the peptide nanotubes can easily be dissolved in several solvents including water. It is therefore of critical importance that the stability of the nanotubes in solution and not after solvent evaporation be investigated prior to applications in which the nanotube will be submerged in liquid. The present article reports results demonstrating the instability and suggests a possible approach to a stabilization procedure, which drastically improves the stability of the formed structures. The results presented herein provide new information regarding the stability of self-organizing diphenylalanine nanotubes in solution.
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| 7. |
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| 8. |
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| 9. |
- Andersson, Håkan S., 1967-, et al.
(author)
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The toxicity of ribbon worms: alpha-nemertides or tetrodotoxin, or both?
- 2016
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In: Planta Medica. - : Georg Thieme Verlag KG. - 0032-0943 .- 1439-0221. ; 82:Supplement 1
-
Journal article (other academic/artistic)abstract
- The marine ribbon worms (nemerteans) are predators which capture their prey by everting a proboscis carrying a mixture of toxins which brings on rapid paralysis [1]. Moreover, ribbon worms have a thick layer of epidermal mucus of similar constitution. Tetrodotoxin (TTX) has been identified as one of these toxins [2]. The extreme toxicity of TTX (lethal by ingestion of 0.5-2 mg) is due to its ability to block voltage-gated sodium channels. Although several bacterial species (among these Vibrio sp.) have been linked to its synthesis, the biogenic origin and biosynthesis is unclear. One hypothesis is that TTX production occurs in a symbiotic relationship with its host, in this case the ribbon worm [3]. We have made significant effort to identify TTX in a setup for production through the cultivation of Vibrio alginolyticus in nutrient broth infused with mucus from the ribbon worm Lineus longissimus. Toxicity was demonstrated by fraction injections into shore crabs, but no TTX was found, and it could be shown conclusively that toxicity was unrelated to TTX and the Vibrio culture itself, and rather a constituent of the ribbon worm mucus [4]. The following studies led us to the discovery of a new class of peptides, the alpha-nemertides, in the mucus of the ribbon worms, which could be directly linked to the toxic effects. A literature review of the available evidence for TTX in ribbon worms show that the evidence in most cases are indirect, although notable exceptions exist. This points to the necessity to further investigate the presence and roles of TTX and alpha-nemertides in ribbon worms.
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| 10. |
- Arvidsson, Ida, et al.
(author)
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Shiga toxin-induced complement-mediated hemolysis and release of complement-coated red blood cell-derived microvesicles in hemolytic uremic syndrome.
- 2015
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In: Journal of Immunology. - : The American Association of Immunologists. - 1550-6606 .- 0022-1767. ; 194:5, s. 2309-2318
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Journal article (peer-reviewed)abstract
- Shiga toxin (Stx)-producing Escherichia coli (STEC) cause hemolytic uremic syndrome (HUS). This study investigated whether Stx2 induces hemolysis and whether complement is involved in the hemolytic process. RBCs and/or RBC-derived microvesicles from patients with STEC-HUS (n = 25) were investigated for the presence of C3 and C9 by flow cytometry. Patients exhibited increased C3 deposition on RBCs compared with controls (p < 0.001), as well as high levels of C3- and C9-bearing RBC-derived microvesicles during the acute phase, which decreased after recovery. Stx2 bound to P1 (k) and P2 (k) phenotype RBCs, expressing high levels of the P(k) Ag (globotriaosylceramide), the known Stx receptor. Stx2 induced the release of hemoglobin and lactate dehydrogenase in whole blood, indicating hemolysis. Stx2-induced hemolysis was not demonstrated in the absence of plasma and was inhibited by heat inactivation, as well as by the terminal complement pathway Ab eculizumab, the purinergic P2 receptor antagonist suramin, and EDTA. In the presence of whole blood or plasma/serum, Stx2 induced the release of RBC-derived microvesicles coated with C5b-9, a process that was inhibited by EDTA, in the absence of factor B, and by purinergic P2 receptor antagonists. Thus, complement-coated RBC-derived microvesicles are elevated in HUS patients and induced in vitro by incubation of RBCs with Stx2, which also induced hemolysis. The role of complement in Stx2-mediated hemolysis was demonstrated by its occurrence only in the presence of plasma and its abrogation by heat inactivation, EDTA, and eculizumab. Complement activation on RBCs could play a role in the hemolytic process occurring during STEC-HUS.
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| 11. |
- Arvidsson, Martin, 1990-
(author)
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Beyond Generative Sufficiency : On Interactions, Heterogeneity & Middle-Range Dynamics
- 2022
-
Doctoral thesis (other academic/artistic)abstract
- Explaining how properties at the level of individuals translate into properties at the level of collectives is a core objective of sociology. Because the social world is characterized by complex webs of social interdependencies, establishing how micro and macro are related to one another requires a detailed understanding of how individuals are influenced by their social environments and the consequences that such influences have for the dynamics of the social process. However, until very recently, it has been difficult to conduct detailed empirical investigations of micro-macro linkages due to the lack of large-scale data containing information on how individuals interact with one another. In the absence of such data, substantive research has tended to (a) focus its attention elsewhere: studying how social factors influence individual outcomes, rather than how actors in interaction with one another bring about collective outcomes, or (b) propose models of micro-macro linkages that—for reasons of parsimony and tractability—often assume artificially high levels of homogeneity. Against this background, this thesis sets out to investigate, first, how the data and tools that have emerged from the digital and computational revolution can help sociologists construct empirically well-founded mappings from the micro to the macro level, and second, how the conclusions about the role of social interdependencies and networks change when the analysis is informed by real-world heterogeneities.In the introductory chapter, a conceptual and analytical framework for studying micro-macro processes is proposed that integrates the theoretical principles of analytical sociology with the data and methods of computational social science. This framework constitutes the foundation of the thesis. It is used in Essays I-III, and it is methodologically built upon in Essay IV.In Essay I, the role of social networks in labor-market segregation processes is examined. Scholarship on labor-market segregation commonly assume that social networks have a segregating effect because of homophilous selection tendencies in network-based recruitment. Using large-scale register data and focusing attention on individuals’ heterogenous opportunities to form same-category ties in different workplaces, Essay I finds that opportunity structures often dominate homophilic preferences. In particular, a mechanism is identified which shows—in contradiction with the main tenet of previous research—that networks often reduce rather than increase segregation by triggering mobility events that counteract the impact of segregating mobility events.Essay II examines the conditions under which social influence can decouple adoption behaviour from individual preferences and thereby bring about unexpected collective outcomes. Prior research has shown that such decoupling can occur, but conflicting evidence and implicit assumptions of strong homogeneity mean that we still know little about the conditions under which this is likely to occur in the real world. Addressing these limitations, this study uses fine-grained, real-world behavioural data from Spotify to estimate heterogeneous social influence effects conditional on properties of individuals’ social environments, and then examine their macro-implications in empirically calibrated simulations. It is found that partial overlap in preferences and strong social ties between the senders and receivers of social influence is needed for social influence to produce decoupling.Essay III centers on the phenomenon of urban scaling and examines the relationship between within-city and between-city inequality. Previous urban scaling research has documented how cities’ total outputs increase more than proportionally with city size and has proposed theoretical models which demonstrate impressive predictive accuracy at aggregate levels. However, this research has overlooked the stark inequalities that exist within cities. Using microdata from multiple countries, it is found that between 36–80% of the previously reported scaling effects can be explained by differences in the distributional tails of cities. Providing explanatory depth to these findings, a cumulative advantage mechanism is identified which elucidates one important channel through which differences in the size of cities’ tails emerge.In Essay IV, a method is proposed for inferring theoretically meaningful dimensions from complex high-dimensional data such as text. The results show that the method captures latent semantic concepts better than or on-par with the current state of the art. For the study of social interactions, the method constitutes a new and potentially important tool for inferring theoretically meaningful dimensions about individuals and their social environments, and in so doing, improves our ability to adjust for specific types of homophily and enables richer and more precise measures of heterogeneity in social interaction processes.
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| 12. |
- Arvidsson, Martin, et al.
(author)
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The Trojan-horse mechanism : How networks reduce gender segregation
- 2021
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In: Science Advances. - : American Association for the Advancement of Science. - 2375-2548. ; 7:16
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Journal article (peer-reviewed)abstract
- The segregation of labor markets along ethnic and gender lines is socially highly consequential, and the social science literature has long viewed homophily and network-based job recruitments as some of its most crucial drivers. Here, we focus on a previously unidentified mechanism, the Trojan-horse mechanism, which, in contradiction to the main tenet of previous research, suggests that network-based recruitment reduce rather than increase segregation levels. We identify the conditions under which networks are desegregating, and using unique data on all individuals and all workplaces located in the Stockholm region during the years 2000-2017, we find strong empirical evidence for the Trojan-horse mechanism and its role in the gender segregation of labor markets.
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| 13. |
- Basheer, Shabana, et al.
(author)
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A membrane protein based biosensor: Use of a phosphate - H+ symporter membrane protein (Pho84) in the sensing of phosphate ions.
- 2011
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In: Biosensors & bioelectronics. - : Elsevier. - 0956-5663 .- 1873-4235. ; 27:1, s. 58-63
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Journal article (peer-reviewed)abstract
- A label free biosensor for direct detection of inorganic phosphate based on potential-step capacitance measurements has been developed. The high-affinity Pho84 plasma membrane phosphate/proton symporter of Saccharomyces cerevisiae was used as a sensing element. Heterologously expressed and purified Pho84 protein was immobilized on a self-assembled monolayer (SAM) on a capacitance electrode. Changes in capacitance were recorded upon exposure to phosphate compared to the control substance, phosphate analogue methylphosphonate. Hence, even without the explicit use of lipid membranes, the Pho84 membrane protein could retain its capacity of selective substrate binding, with a phosphate detection limit in the range of the apparent in vivo K(m). A linear increase in capacitance was monitored in the phosphate concentration range of 5-25 mu M. The analytical response of the capacitive biosensor is in agreement with that the transporter undergoes significant conformational changes upon exposure to inorganic phosphate, while exposure to the analogue only causes minor responses.
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| 14. |
- Bergdahl, Gizem Ertürk, et al.
(author)
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Bisphosphonate Ligand Mediated Ultrasensitive Capacitive Protein Sensor : Complementary Match of Supramolecular and Dynamic Chemistry
- 2019
-
In: New Journal of Chemistry. - : Royal Society of Chemistry. - 1144-0546 .- 1369-9261. ; 43:2, s. 847-852
-
Journal article (peer-reviewed)abstract
- Modern healthcare demands rapid and accurate detection of proteins/enzymes at the ultratrace level. Herein we present a molecularly imprinted capacitive sensor for Trypsin, developed by microcontact imprinting. High affinity and selectivity was achieved by doping the prepolymerization mixture with a stoichiometric amount of methacrylamide-based bisphosphonate (BP) monomer. Taking advantage of the strong interaction of bisphosphonate with lysine/arginine residues on the surface of Trypsin, we have constructed a powerful polymeric sensor. The BP based sensor has the ability to recognize trypsin over other arginine-rich proteins, even in high ionic strength buffers with a sub-picomolar detection limit (pM). We believe that the combination of supramolecular chemistry, molecular imprinting and advanced instrumentation has a potential for future drug development and diagnostics that extends beyond biomolecular recognition.
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| 15. |
- Bergdahl, Gizem Ertürk, et al.
(author)
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Capacitive Saccharide Sensor Based on Immobilized Phenylboronic Acid with Diol Specificity
- 2019
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In: Applied Biochemistry and Biotechnology. - : Springer Science and Business Media LLC. - 0273-2289 .- 1559-0291. ; 188:1, s. 124-137
-
Journal article (peer-reviewed)abstract
- A capacitive sensor for saccharide detection is described in this study. The detection is based on selective interaction between diols and aminophenylboronic acid (APBA) immobilized on a gold electrode. Glucose, fructose, and dextran (MW: 40 kDa) were tested with the system over wide concentration ranges (1.0 x 10−8 M - 1.0 x 10−3 M for glucose, 1.0 x 10−8 M - 1.0 x 10−2 M for fructose and 1.0 x 10−10 M - 1.0 x 10−5 M for dextran). The limits of detection (LODs) were 0.8 nM for glucose, 0.6 nM for fructose, and 13 pM for dextran. These data were comparable to the others reported previously. In order to demonstrate glycoprotein detection with the same sensor, human immunoglobulin G (IgG) as well as horseradish peroxidase were used as model analytes. The sensor responded to IgG in the concentration range of 1.0 x 10−13 M - 1.0 x 10−7 M with a LOD value of 16 fM. The performance of the assay of peroxidase was compared to a spectrophotometric assay by determining the enzymatic activity of a captured analyte. The results showed that the method might be useful for label-free, fast, and sensitive detection of saccharides as well as glycoproteins over a wide concentration range.
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| 16. |
- Bergdahl, Gizem Ertürk, et al.
(author)
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Capacitive Sensor to Monitor Enzyme Activity by Following Degradation of Macromolecules in Real Time
- 2019
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In: Applied Biochemistry and Biotechnology. - : Springer Science and Business Media LLC. - 0273-2289 .- 1559-0291. ; 189, s. 374-383
-
Journal article (peer-reviewed)abstract
- A capacitive sensor was developed to analyze the presence and enzymatic activity of a model protease from standard solutions by following the degradation of the substrate in real time. The enzyme was chosen based on its specific digestion of the hinge region of immunoglobulin G (IgG). Real-time enzyme activity was monitored by measuring the change in capacitance (∆C) based on the release of IgG fragments after enzymatic digestion by the enzyme. The results indicated that the developed capacitive system might be used successfully for label-free and real-time monitoring of enzymatic activity of different enzymes in a sensitive, rapid, and inexpensive manner in biotechnological, environmental, and clinical applications.
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| 17. |
- Cain, Peter A, et al.
(author)
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Age and gender specific normal values of left ventricular mass, volume and function for gradient echo magnetic resonance imaging: a cross sectional study.
- 2009
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In: BMC medical imaging. - : Springer Science and Business Media LLC. - 1471-2342. ; 9:2
-
Journal article (peer-reviewed)abstract
- Knowledge about age-specific normal values for left ventricular mass (LVM), end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV) and ejection fraction (EF) by cardiac magnetic resonance imaging (CMR) is of importance to differentiate between health and disease and to assess the severity of disease. The aims of the study were to determine age and gender specific normal reference values and to explore the normal physiological variation of these parameters from adolescence to late adulthood, in a cross sectional study.
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| 18. |
- Cain, Peter, et al.
(author)
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Physiological determinants of the variation in left ventricular mass from early adolescence to late adulthood in healthy subjects
- 2005
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In: Clin Physiol Funct Imaging. - 1475-0961. ; 25:6, s. 332-9
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Journal article (peer-reviewed)abstract
- BACKGROUND: The physiological determinants of left ventricular mass (LVM) measured by cardiac magnetic resonance (CMR) imaging are not well defined as prior investigators have studied either adults or adolescents in isolation or have not strictly excluded hypertension or accounted for the effects of exercise habits, haemodynamic, demographic, or body shape characteristics. METHODS: A total of 102 healthy volunteers (12-81 years, 53 males) underwent CMR. All parameters [unstandardized and adjusted for body surface area (BSA)] were analysed according to gender and by adolescence versus adulthood (adolescents <20 years, adults > or = 20 years). The influence of haemodynamic factors, exercise, and demographic factors on LVM were determined with multivariate linear regression. Results: LVM rose during adolescence and declined in adulthood. LVM and LVMBSA were higher in males both in adults (LVM: 188 +/- 22 g versus 139 +/- 21 g, P < 0.001; LVMBSA: 94 +/- 11 g m(-2) versus 80 +/- 11 g m(-2), P < 0.001) and in adolescents when adjusted for BSA (LVM: 128 +/- 29 g versus 107 +/- 20 g, P = 0.063; LVMBSA: 82 +/- 8 g m(-2) versus 71 +/- 10 g m(-2), P = 0.025). In adults, systolic blood pressure (SBP) and self-reported physical activity increased while meridional and circumferential wall stress were constant with age. Multivariate regression analysis revealed age, gender, and BSA as the major determinants of LVM (global R2 = 0.69). CONCLUSIONS: Normal LVM shows variation over a broad age range in both genders with a rise in adolescence and subsequent decline with increasing age in adulthood despite an increase in SBP and physical activity. BSA, age, and gender were found to be major contributors to the variation in LVM in healthy adults, while haemodynamic factors, exercise, and wall stress were not.
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| 19. |
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| 20. |
- Canfarotta, Francesco, et al.
(author)
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A Novel Capacitive Sensor Based on Molecularly Imprinted Nanoparticles as Recognition Elements
- 2018
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In: Biosensors and Bioelectronics. - : Elsevier BV. - 0956-5663. ; , s. 108-114
-
Journal article (peer-reviewed)abstract
- Molecularly Imprinted Polymers (MIPs) are synthetic receptors capable of selective binding to their target (template) molecules and, hence, are used as recognition elements in assays and sensors as a replacement for relatively unstable enzymes and antibodies. Herein, we describe a manufacturing-friendly protocol for integration of MIP nanoparticles (nanoMIPs) with a (label-free) capacitive sensor. The nanoMIPs were produced by solid-phase synthesis for two templates with different sizes and properties, including a small molecule tetrahydrocannabinol (THC) and a protein (trypsin). NanoMIPs were deposited on the surface of the sensor and the change in capacitance (ΔC) upon binding of the target was measured. The significant improvement in the selectivity and limit of detection (one order of magnitude compared to previously used MIP microparticles) can be attributed to their increased surface-to-volume ratio and higher specificity of the nanoMIPs produced by the solid-phase method. The methodology described is also compatible with common sensor fabrication approaches, as opposed to methods involving in situ MIP polymerisation. The proposed sensor shows high selectivity, fast sensor response (45 min including injection, regeneration and re-equilibration with running buffer), and straightforward data analysis, which makes it viable for label-free monitoring in real-time. The set of targets assessed in this manuscript shows the general applicability of the biosensor platform.
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| 21. |
- Dainiak, Maria, et al.
(author)
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Improved methods for prepurification and detection of Staphylococcal Enterotoxin B from cell-free culture filtrate
- 2005
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In: Biotechnology Progress. - : Wiley. - 1520-6033 .- 8756-7938. ; 21:4, s. 1347-1351
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Journal article (peer-reviewed)abstract
- An improved ELISA method for the detection of Staphylococcal. Enterotoxin B (SEB) in protein A preparations is presented. Fab fragments were obtained by digestion with papain of anti-SEB IgG bound to SEB immobilized on Sepharose 4B. Anti-SEB and peroxidase-labeled Fab fragments from secondary antibodies were successfully used in a modified ELISA of SEB in protein A preparations. SEB-Sepharose was used repeatedly for the production of anti-SEB Fab fragments by papain digestion without loss of affinity. In addition, for the purification of SEB from crude culture filtrates, an initial step utilizing a combined heat and pH treatment for the removal of significant amounts of contaminating proteins without losses of toxin activity is presented. This pretreatment step yielded positive effects in further downstream processing considering both shortened time and an increase in total recovery.
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| 22. |
- Deraz, Sahar, et al.
(author)
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Production and physicochemical characterization of acidocin D20079, a bacteriocin produced by Lactobacillus acidophilus DSM 20079
- 2007
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In: World Journal of Microbiology & Biotechnology. - : Springer Science and Business Media LLC. - 0959-3993 .- 1573-0972. ; 23:7, s. 911-921
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Journal article (peer-reviewed)abstract
- Lactobacillus acidophilus DSM 20079 is the producer of a novel bacteriocin termed acidocin D20079. In this paper, a partial sequence of this peptide is determined, together with data on its secondary structure. A modification of the MRS-growth medium (replacing the detergent Tween 80 with oleic acid), was shown to improve the production level of the peptide by one order of magnitude, as well as to stabilize the activity level. Addition of a detergent (Tween 20, less interfering in mass spectrometric analysis), was however necessary for solubilization of the purified acidocin D20079. Digestion of the peptide followed by de-novo sequencing of generated fragments, allowed determination of a partial sequence consisting of 39 of the totally estimated 65 residues. Acidocin D20079 has a high content of glycine residues, hydrophobic residues, and acidic residues. No modified amino acids were found. Edman degradation, and C-terminal sequencing failed, suggesting that the peptide may be cyclic, and a novel member of class IIc bacteriocins. Circular dichroism spectroscopy and secondary structure prediction showed random coil conformation in aqueous solution, but secondary structure was induced in the presence of sodium-dodecyl sulfate. The data could be fitted assuming 2-13% of the residues to be in alpha-helix and 23-27% of the residues to be in beta-strand conformation. This indicates that a membrane/membrane-mimicking hydrocarbon-water interface induces an active conformation.
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| 23. |
- Deraz, Sahar, et al.
(author)
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Purification and characterisation of acidocin D20079, a bacteriocin produced by Lactobacillus acidophilus DSM 20079
- 2005
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In: Journal of Biotechnology. - : Elsevier BV. - 1873-4863 .- 0168-1656. ; 117:4, s. 343-354
-
Journal article (peer-reviewed)abstract
- Bacteriocins are natural antimicrobial agents produced by food fermentative bacteria. Lactobacillus acidophilus DSM 20079 produces a small bacteriocin, with a molecular mass of 6.6 kDa, designated acidocin D20079. This antimicrobial peptide was extremely heat-stable (30 min at 121 degrees C) and was active over a wide pH range. It was found to be sensitive to proteolytic enzymes (trypsin, ficin, pepsin, papain, and proteinase K). Acidocin D20079 has a narrow inhibitory spectrum restricted to the genus Lactobacillus which includes L. sakei NCDO 2714, an organism known to cause anaerobic spoilage of vacuum-packaged meat. Maximum production of acidocin D20079 in MRS broth was detected at pH 6.0, and the peptide was purified by ammonium sulphate precipitation followed by sequential cation exchange and hydrophobic interaction chromatography. Purified acidocin D20079 spontaneously formed spherulite crystals during dialysis. As the N-terminus was found to be blocked for sequencing, matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry was used to determine a partial sequence. and the molecular mass of the bacteriocin in the formed crystals (6.6 kDa). Estimates of the molecular weight of the partially purified peptide, using tricine-SDS-PAGE, in which bacteriocin activity was confirmed by overlayer techniques were in accordance with this value. (c) 2005 Published by Elsevier B.V.
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| 24. |
- Dugic, Izudin, 1962-, et al.
(author)
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Non-metallic inclusion and their effect on fatigue strength for case-hardened carbon steel in gears
- 2018
-
In: TMS 2018 147th Annual Meeting & Exhibition Supplemental Proceedings. TMS 2018. - Cham : Springer. - 9783319725253 ; , s. 123-133
-
Conference paper (peer-reviewed)abstract
- Steel is a very essential structural material and its production worldwide has shown significant increase over the last years. In steels there always exist a large number of inclusions which can have a degrading effect on the fatigue properties. This study is focused on the link between the characteristics of non-metallic inclusions and how they affect fatigue strength of the standardized case-hardened carbon steel 20MnCr5 and a version of this steel with a more favorable inclusion distribution, a so-called Clean steel. For the evaluation of the mechanical properties the test result from rotary bending tests are compared and an improvement by 37.5% in fatigue strength can be noted between the different steels. The new performed ultrasonic tests illustrate the difference in the size of defects in materials with different manufacturing processes and degree of reduction. By studying international and European standards for non-destructive testing and investigation of alloy compounds, the current material specification can be adjusted. © The Minerals, Metals & Materials Society 2018.
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| 25. |
- Elovson Grey, Carl, et al.
(author)
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A mass spectrometric investigation of native and oxidatively inactivated chloroperoxidase
- 2007
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In: ChemBioChem. - : Wiley. - 1439-4227 .- 1439-7633. ; 8:9, s. 1055-1062
-
Journal article (peer-reviewed)abstract
- The enzyme chloroperoxidase (CPO) found in Calclariomyces fumago is able to catalyze several stereoselective oxidation reaction by using a dean oxidant, usually hydrogen peroxide (H2O2), without the need for expensive cofactor generation. CPO's lack of operational stability however, is a major limitation for its commercial use. In the present study, a capillary-LC on-line trypsin- digestion system combined with reversed-phase chromatography and mass spectrometric detection was optimized for studying the primary sequence of CPO. Samples containing native CPO, CPO treated with H2O2, and CPO oxidatively inactivated by the use of indole and H2O2 were analyzed and compared. Three oxidized peptides were found in the samples treated with H2O2. Two additional oxidized peptides were found in the CPO samples that were completely inactivated, one of which contained an oxidized cysteine residue, Cys50, which is an essential amio acid due to its function as the axial ligand to the iron in the heme - the prosthetic group in CPO. In addition, the heme group was absent in the inactivated samples but was readily detected in other samples.
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| 26. |
- Engblom, Henrik, et al.
(author)
-
The endocardial extent of reperfused first-time myocardial infarction is more predictive of pathologic Q waves than is infarct transmurality: a magnetic resonance imaging study.
- 2007
-
In: Clinical Physiology and Functional Imaging. - 1475-0961. ; 27:2, s. 101-108
-
Journal article (peer-reviewed)abstract
- Historically, Q-wave myocardial infarction (MI) has been equated with transmural MI. This association have, however, recently been rejected. The endocardial extent of MI is another potential determinant of pathological Q waves, since the first part of the QRS complex where the Q wave appears reflects depolarization of subendocardial myocardium. Therefore, the aim of the present study was to test the hypothesis that endocardial extent of MI is more predictive of pathological Q waves than is MI transmurality and to investigate the relationship between QRS scoring of the ECG and MI characteristics. Twenty-nine patients with reperfused first-time MI were prospectively enrolled. One week after admission, delayed contrast-enhanced magnetic resonance imaging (DE-MRI) was performed and 12-lead ECG was recorded. Size, transmurality and endocardial extent of MI were assessed by DE-MRI. Q waves were identified with Minnesota coding and electrocardiographic MI size was estimated by QRS scoring of the ECG. There was a significant difference between patients with and without Q waves with regard to MI size (P = 0.03) and endocardial extent of MI (P = 0.01), but not to mean and maximum MI transmurality (P = 0.09 and P = 0.14). Endocardial extent was the only independent predictor of pathological Q waves. Endocardial extent of MI was most strongly correlated to QRS score (r = 0.86, P < 0.001) of the MI variables tested. The endocardial extent of reperfused first-time acute MI is more predictive of pathological Q waves than is MI transmurality.
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| 27. |
- Engdahl, Elin, et al.
(author)
-
Increased Serological Response Against Human Herpesvirus 6A Is Associated With Risk for Multiple Sclerosis
- 2019
-
In: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 10
-
Journal article (peer-reviewed)abstract
- Human herpesvirus (HHV)-6A or HHV-6B involvement in multiple sclerosis (MS) etiology has remained controversial mainly due to the lack of serological methods that can distinguish the two viruses. A novel multiplex serological assay measuring IgG reactivity against the immediate-early protein 1 from HHV-6A (IE1A) and HHV-6B (IE1B) was used in a MS cohort (8,742 persons with MS and 7,215 matched controls), and a pre-MS cohort (478 individuals and 476 matched controls) to investigate this further. The IgG response against IE1A was positively associated with MS (OR = 1.55, p = 9 × 10-22), and increased risk of future MS (OR = 2.22, p = 2 × 10-5). An interaction was observed between IE1A and Epstein-Barr virus (EBV) antibody responses for MS risk (attributable proportion = 0.24, p = 6 × 10-6). In contrast, the IgG response against IE1B was negatively associated with MS (OR = 0.74, p = 6 × 10-11). The association did not differ between MS subtypes or vary with severity of disease. The genetic control of HHV-6A/B antibody responses were located to the Human Leukocyte Antigen (HLA) region and the strongest association for IE1A was the DRB1*13:01-DQA1*01:03-DQB1*06:03 haplotype while the main association for IE1B was DRB1*13:02-DQA1*01:02-DQB1*06:04. In conclusion a role for HHV-6A in MS etiology is supported by an increased serological response against HHV-6A IE1 protein, an interaction with EBV, and an association to HLA genes.
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| 28. |
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| 29. |
- Erlandsson, Dag, et al.
(author)
-
Automated flow-injection immunosensor based on current pulse capacitive measurements
- 2014
-
In: Sensors and Actuators B: Chemical. - : Elsevier BV. - 0925-4005. ; 190, s. 295-304
-
Journal article (peer-reviewed)abstract
- This document describes a new concept for assessing capacitance based on a constant current pulse to the biosensor transducer. The biosensor has a working electrode that is coated with an insulating molecular layer including a ligand which forms an affinity surface. A sensor electrode is brought into contact with electrolyte solution, and the new measuring principle then involves steps where three different constant currents (I-1, I-2 and I-3) are serially pulsed on the sensor surface during pre-determined time periods. The potential that is built up (rising) across the sensor surface is sampled every 6.8 mu s. The inclination of the registered potential profile corresponding to the current pulsed was utilized to calculate both capacitance and resistance. The new current-based measurement method shows a 10-fold increase in stability for the capacitive measurement as compared to the potential pulse technique. Quantitation of HIV-1 p24 using monoclonal anti-HIV-1 p24 antibodies was used as a model system for the evaluation of the technique. The binding of HIV-1 p24 antigens to the immobilized antibodies causes the capacitance to decrease. The change in capacitance was proportional to the concentration of HIV-1 p24. The capacitance measurement using the current pulse method offers a stable sensing technique with a broad range of potential applications. (C) 2013 Elsevier B. V. All rights reserved.
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| 30. |
- Ertürk, Gizem, et al.
(author)
-
A sensitive and real-time assay of trypsin by using molecular imprinting-based capacitive biosensor
- 2016
-
In: Biosensors and Bioelectronics. - : Elsevier BV. - 0956-5663. ; 86, s. 557-565
-
Journal article (peer-reviewed)abstract
- Use of a highly sensitive, selective capacitive biosensor is reported for label-free, real-time, easy and rapid detection of trypsin by using the microcontact imprinting method. Real-time trypsin detection was performed with trypsin-imprinted (trypsin-MIP) capacitive electrodes using standard trypsin solutions in the concentration range of 1.0×10−13–1.0×10−7 M with a detection limit of 3.0×10−13 M. Selectivity and cross-reactivity of the system were tested by using competing proteins including chymotrypsin (chy), bovine serum albumin (BSA), lysozyme (lyz) and cytochrome c (cyt c) in singular and competitive manner and the selectivity of the system was determined with the selectivity coefficients of approximately 705.1, 6.5, 6.4 and 5.1 for chy, BSA, lyz and cyt c, respectively. The trypsin-MIP capacitive electrode was used for ~80 assays during 2 months and retained its binding property during all that time with a decrease of approximately 2.3% in the signal amplitude. In the last step, trypsin activity was measured by using Nα-Benzoyl-D, L-arginine 4-nitroanilide hydrochloride (BAPNA) as the substrate with spectrophotometer at 410 nm. The trypsin activity was measured as 9 mU/mL by spectrophotometer while the amount of captured enzyme calculated from the capacitive system was 7.9 mU/mL which shows the correlation between two methods. From the comparison it is obvious that the new method is an attractive alternative for assaying trypsin and the developed capacitive system might be used successfully to monitor label-free, real-time enzymatic activity of different proteases in a sensitive, rapid, cost-effective manner for different applications.
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| 31. |
- Ertürk, Gizem, et al.
(author)
-
Bisphosphonate ligand mediated ultrasensitive capacitive protein sensor : complementary match of supramolecular and dynamic chemistry
- 2018
-
In: New Journal of Chemistry. - : Royal Society of Chemistry (RSC). - 1144-0546 .- 1369-9261. ; 43:2, s. 847-852
-
Journal article (peer-reviewed)abstract
- Modern healthcare demands rapid and accurate detection of proteins/enzymes at the ultratrace level. Herein we present a molecularly imprinted capacitive sensor for trypsin, developed by microcontact imprinting. High affinity and selectivity was achieved by doping the prepolymerization mixture with a stoichiometric amount of methacrylamide-based bisphosphonate (BP) monomer. Taking advantage of the specific interaction between bisphosphonate binding monomers and lysine/arginine residues on the surface of trypsin, we have constructed a powerful polymeric sensor. The BP based sensor has the ability to recognize trypsin over other arginine-rich proteins, even in high ionic strength buffers with a sub-picomolar detection limit (pM). We believe that the combination of supramolecular chemistry, molecular imprinting and advanced instrumentation has a potential for future drug development and diagnostics that extends beyond biomolecular recognition.
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| 32. |
- Ertürk, Gizem, et al.
(author)
-
Highly sensitive detection and quantification of the secreted bacterial benevolence factor RoxP using a capacitive biosensor : A possible early detection system for oxidative skin diseases
- 2018
-
In: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 13:3
-
Journal article (peer-reviewed)abstract
- The impact of the microbiota on our health is rapidly gaining interest. While several bacteria have been associated with disease, and others being indicated as having a probiotic effect, the individual biomolecules behind these alterations are often not known. A major problem in the study of these factors in vivo is their low abundance in complex environments. We recently identified the first secreted bacterial antioxidant protein, RoxP, from the skin commensal Propionibacterium acnes, suggesting its relevance for maintaining the redox homeostasis on the skin. In order to study the effect, and prevalence, of RoxP in vivo, a capacitive biosensor with a recognition surface based on molecular imprinting was used to detect RoxP on skin in vivo. In vitro analyses demonstrated the ability to detect and quantify RoxP in a concentration range of 1 x 10(-13) M to 1 x 10(-8) M from human skin swabs; with a limit of detection of 2.5 x 10(-19) M in buffer systems. Further, the biosensor was highly selective, not responding to any other secreted protein from P. acnes. Thus, it was possible to demonstrate the presence, and quantity, of RoxP on human skin. Therefore, the developed biosensor is a very promising tool for the detection of RoxP from clinical samples, offering a rapid, cost-effective and sensitive means of detecting low-abundant bacterial proteins in vivo in complex milieus.
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| 33. |
- Ertürk, Gizem, et al.
(author)
-
Microcontact-BSA imprinted capacitive biosensor for real-time, sensitive and selective detection of BSA
- 2014
-
In: Biotechnology Reports. - : Elsevier BV. - 2215-017X. ; 3, s. 65-72
-
Journal article (peer-reviewed)abstract
- An analytical method is presented, combining novel microcontact imprinting technique and capacitive biosensor technology for the detection of BSA. Glass cover slips were used for preparation of protein stamps. The microcontact-BSA imprinted gold electrodes were prepared in the presence of methacrylic acid (MAA) and poly-ethylene glycol dimethacrylate (PEGDMA) as the cross-linker by bringing the protein stamp and the gold electrode into contact under UV-polymerization. Real-time BSA detection studies were performed in the concentration range of 1.0 × 10-20-1.0 × 10-8 M with a limit of detection (LOD) of 1.0 × 10-19 M. Cross-reactivity towards HSA and IgG were 5 and 3%, respectively. The electrodes were used for >70 assays during 2 months and retained their binding properties during all that time. The NIP (non-imprinted) electrode was used as a reference. The microcontact imprinting technology combined with the biosensor applications is a promising technology for future applications.
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| 34. |
- Erturk, Gizem, et al.
(author)
-
Real-time prostate-specific antigen detection with prostate-specific antigen imprinted capacitive biosensors
- 2015
-
In: Analytica Chimica Acta. - : Elsevier BV. - 1873-4324 .- 0003-2670. ; 891, s. 120-129
-
Journal article (peer-reviewed)abstract
- Prostate specific antigen (PSA) is a valuable biomarker for early detection of prostate cancer, the third most common cancer in men. Ultrasensitive detection of PSA is crucial to screen the prostate cancer in an early stage and to detect the recurrence of the disease after treatment. In this report, microcontact-PSA imprinted (PSA-MIP) capacitive biosensor chip was developed for real-time, highly sensitive and selective detection of PSA. PSA-MIP electrodes were prepared in the presence of methacrylic acid (MAA) as the functional monomer and ethylene glycol dimethacrylate (EGDMA) as the cross-linker via UV polymerization. Immobilized Anti-PSA antibodies on electrodes (Anti-PSA) for capacitance measurements were also prepared to compare the detection performances of both methods. The electrodes were characterized by atomic force microscopy (AFM), scanning electron microscopy (SEM) and cyclic voltammetry (CV) and real-time PSA detection was performed with standard PSA solutions in the concentration range of 10 fg mL(-1) -100 ng mL(-1). The detection limits were found as 8.0 x 10(-5) ng mL(-1) (16 x 10(-17) M) and 6.0 x 10(-4) ng mL(-1) (12 x 10(-16) M) for PSA-MIP and Anti-PSA electrodes, respectively. Selectivity studies were performed against HSA and IgG and selectivity coefficients were calculated. PSA detection was also carried out from diluted human serum samples and finally, reproducibility of the electrodes was tested. The results are promising and show that when the sensitivity of the capacitive system is combined with the selectivity and reproducibility of the microcontact-imprinting procedure, the resulting system might be used successfully for real-time detection of various analytes even in very low concentrations. (C) 2015 Elsevier B.V. All rights reserved.
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| 35. |
- Foubert, Astrid, et al.
(author)
-
Antibody immobilization strategy for the development of a capacitive immunosensor detecting zearalenone
- 2019
-
In: Talanta. - : Elsevier BV. - 0039-9140. ; 191, s. 202-208
-
Journal article (peer-reviewed)abstract
- A highly sensitive flow-injection capacitive immunosensor was developed for detection of the mycotoxin zearalenone (ZEN). Different strategies for immobilization of an anti-ZEN antibody on the surface of a gold electrode, i.e. polytyramine or self-assembled monolayers (SAMs) of 3-mercaptopropionic acid (3-MPA) and lipoic acid (LA), were used and their performances were compared. The LA- and 3-MPA-based systems showed broad linear ranges for ZEN determination, i.e. from 0.010 nM to 10 nM and from 0.020 nM to 10 nM, respectively. Under optimal conditions, the LA-based immunosensor was capable of performing up till 13 regeneration-interaction cycles (with use of glycine HCl, pH 2.4) with a limit of detection (LOD) of 0.0060 nM, equivalent to 1.9 pg mL−1. It also demonstrated a good inter-assay precision (RSD < 10%). However, the tyramine-based capacitive immunosensor showed a bad repeatability (only 4 regeneration-interaction cycles were possible) and inter-assay precision (RSD > 15%) which did not allow sensitive and precise measurements. The LA-based method was compared with a direct ELISA. These results demonstrated that the label-free developed capacitive immunosensor had a better sensitivity and shorter analysis time in comparison with the direct microwell-plate format.
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| 36. |
- Goswami, Sreetosh, et al.
(author)
-
Charge disproportionate molecular redox for discrete memristive and memcapacitive switching
- 2020
-
In: Nature Nanotechnology. - : Springer Science and Business Media LLC. - 1748-3387 .- 1748-3395. ; 15:5, s. 380-389
-
Journal article (peer-reviewed)abstract
- Electronic symmetry breaking by charge disproportionation results in multifaceted changes in the electronic, magnetic and optical properties of a material, triggering ferroelectricity, metal/insulator transition and colossal magnetoresistance. Yet, charge disproportionation lacks technological relevance because it occurs only under specific physical conditions of high or low temperature or high pressure. Here we demonstrate a voltage-triggered charge disproportionation in thin molecular films of a metal-organic complex occurring in ambient conditions. This provides a technologically relevant molecular route for simultaneous realization of a ternary memristor and a binary memcapacitor, scalable down to a device area of 60 nm(2). Supported by mathematical modelling, our results establish that multiple memristive states can be functionally non-volatile, yet discrete-a combination perceived as theoretically prohibited. Our device could be used as a binary or ternary memristor, a binary memcapacitor or both concomitantly, and unlike the existing 'continuous state' memristors, its discrete states are optimal for high-density, ultra-low-energy digital computing. Charge disproportionation in thin molecular films of a metal-organic complex enables the realization of a ternary memristor and binary memcapacitor.
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| 37. |
- Gunasekara, Saman Nimali, 1982-, et al.
(author)
-
The Experimental Phase Diagram Study of the Binary Polyols System Erythritol-Xylitol
- 2017
-
In: Solar Energy Materials and Solar Cells. - : Elsevier. - 0927-0248 .- 1879-3398. ; 174, s. 248-262
-
Journal article (peer-reviewed)abstract
- A comprehensive phase diagram for the binary polyols system erythritol-xylitol has been mapped with a transparent characterization approach. Here, the phase equilibrium of the system has been studied experimentally using a combination of methods: Temperature-history (T-history), X-Ray Diffraction (XRD), and Field-Emission Scanning Electron Microscopy (FESEM), and linked to Tammann plots. Existing literature has previously shown the system to be a non-isomorphous type forming a simple eutectic, by combining experimental data with theoretical modelling. The present investigation shows that the system’s phase diagram is a partially isomorphous type forming a eutectic, but not a non-isomorphous type forming a simple eutectic. Here, the eutectic was found within 25-30 mol% erythritol and at 77 °C, which differs from the previous studies identifying the eutectic respectively at 25 or 36 mol% erythritol and at 82 °C. The reasons for the differences are hard to deduce since the research approach is not presented as fully transparent from the past studies. In the present study, only the temperature-composition plot of the first melting (of the two components in a physical mix, but not of a single blend) indicated the shape of a simple eutectic in a non-isomorphous system. The cycles after the first melting in contrast started from the real blend, and displayed eutectic and solid-solid phase changes in T-history. These were verified as forming solid solutions with XRD and FESEM. This eutectic melts at a temperature suitable for low-temperature solar heating, but displayed glass transition, supercooling, and thermally activated degradation, thus affecting its practical aspects as a PCM.
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| 38. |
- Gutierrez, Alvaro V R, et al.
(author)
-
Bioimprinting as a tool for the detection of aflatoxin B1 using a capacitive biosensor
- 2016
-
In: Biotechnology Reports. - : Elsevier BV. - 2215-017X. ; 11, s. 12-17
-
Journal article (peer-reviewed)abstract
- A strategy for the detection of aflatoxin B1 using a capacitive biosensor has been studied. The use of proteins for the generation of sites with high specificity against aflatoxin B1 are produced via bioimprinting. This technique has become a tool for the detection of aflatoxin B1 using a capacitive biosensor. The results demonstrate the ability to generate specific interactions with aflatoxin B1 with a linear relation between signals registered and log concentration of the target aflatoxin in the concentration range of 3.2 × 10-6 to 3.2 × 10-9 M when using ovalbumin as framework for the bioimprinting.
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| 39. |
- Hanora, Amro, et al.
(author)
-
Capture of bacterial endotoxins using a supermacroporous monolithic matrix with immobilized polyethyleneimine, lysozyme or polymyxin B
- 2005
-
In: Journal of Biotechnology. - : Elsevier BV. - 1873-4863 .- 0168-1656. ; 118:4, s. 421-433
-
Journal article (peer-reviewed)abstract
- Bacterial endotoxins (BEs) are integrated part of Escherichia coli, a microorganism widely used for the production of recombinant proteins. BEs should be eliminated in the course of down stream processing of target protein produced by these bacteria. Supermacroporous monolith (continuous bed) columns, so called cryogel columns, with immobilized polyethyleneimine (PEI), polymyxin B (PMB) and lysozyme were employed for BEs capture. Due to the large interconnected pores it was possible to use cryogel columns at flow rates as high as 10 ml/min. The columns packed with Sepharose CL-4B with immobilized PEI, PMB and lysozyme were impossible to use at these high flow rates due to the collapse of the bed. The dynamic capacities of the cryogel columns were nearly independent of the flow rate. In the presence of EDTA, BEs were quantitatively captured from mixtures with a model protein, bovine serum albumin (BSA) at pH 7.2 with practically no protein losses. At pH 3.6 BEs were captured directly from non-clarified E. coli cell lysate resulting in more than 104 times BEs clearance. (C) 2005 Elsevier B.V. All rights reserved.
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| 40. |
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| 41. |
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| 42. |
- Hedström, Gustav, et al.
(author)
-
Low expression of microRNA-129-5p predicts poor clinical outcome in diffuse large B cell lymphoma (DLBCL)
- 2013
-
In: International Journal of Hematology. - : Springer Science and Business Media LLC. - 0925-5710 .- 1865-3774. ; 97:4, s. 465-471
-
Journal article (peer-reviewed)abstract
- Diffuse large B cell lymphoma (DLBCL) is a heterogeneous group of B cell lymphomas. MicroRNA expression provides a new and interesting tool for understanding the biology and clinical course of DLBCL. The present study presents microRNA-129-5p expression data from DLBCL patients treated with CHOP or R-CHOP. Patients with low microRNA-129-5p expression had a median survival of 23 months and a significantly shorter overall survival (P = 0.0042) compared to patients with high microRNA-129-5p expression, who had a median survival of 58 months. We also found that patients treated with R-CHOP only and displaying low microRNA-129-5p expression had a significantly shorter overall survival compared to patients with high microRNA-129-5p expression; all such patients were still alive at the time of last follow-up (P = 0.043). No significant difference was found among microRNA-129-5p expression in tumor tissue, the tissue surrounding the tumor, and normal controls. To our knowledge, this is the first report to show that the expression of microRNA-129-5p can affect the clinical outcome of DLBCL patients and that microRNA-129-5p may be involved in the biology of DLBCL development, although larger studies are necessary to confirm this. Further investigations may also help to elucidate the biological role of microRNA-129-5p in DLBCL.
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| 43. |
- Hedström, Gustaf, et al.
(author)
-
Mast cell infiltration is a favourable prognostic factor in diffuse large B-cell lymphoma
- 2007
-
In: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 138:1, s. 68-71
-
Journal article (peer-reviewed)abstract
- Previous studies indicate that the inflammatory response in diffuse large B-cell lymphomas (DLBCL) is important for the clinical outcome. Mast cells are key regulators in this response; we investigated whether the number of tryptase-positive mast cells is correlated with clinical outcome. Patients with many mast cells had a significantly better event-free survival (EFS) compared to those with few mast cells (P < 0.03 in both germinal centre (GC) and non-GC DLBCL. This supports the idea that the infiltration of mast cells is a reflection of the host inflammatory response and is related to a favourable outcome.
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| 44. |
- Hedström, Martin, et al.
(author)
-
Continuous measurements of a binding reaction using a capacitive biosensor
- 2005
-
In: Biosensors & Bioelectronics. - : Elsevier BV. - 1873-4235 .- 0956-5663. ; 21:1, s. 41-48
-
Journal article (peer-reviewed)abstract
- A capacitive biosensor with polyclonal antibodies raised against human serum albumin (HSA) immobilized on a gold transducer has been developed for continuous measurement of HSA in the μM-range. A mathematical model has been refined to describe integral HSA-binding curves assuming that (i) binding is essentially irreversible under the conditions used, (ii) the signal is scaled as the number of non-occupied binding sites and (iii) the rate of disappearance of available binding sites is scaled as the number of available binding sites and analyte concentration in solution. Deconvolution of the curves using the mathematical model indicates clearly that it is possible to retrieve concentration profiles (isocratic, linearly or exponentially increasing gradients) of the analyte in the continuous sample flow from the normalized integral binding (NIB) curves. The data presented constitutes the theoretical background and the first step towards the development of an analytical system allowing on-line detection of the concentration profile of the analyte from NIB-curves. Since the system can be used for extended time periods between regeneration steps, a low frequency of regeneration steps can be expected.
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| 45. |
- Hedström, Martin, et al.
(author)
-
Fast on-column protein digestion with subsequent peptide mapping using tandem mass spectrometry with information dependent acquisition
- 2005
-
In: Journal of Chromatography A. - : Elsevier BV. - 0021-9673. ; 1080:2, s. 117-123
-
Journal article (peer-reviewed)abstract
- A platform for rapid on-line protein digestion of protein mixtures for direct infusion to a mass spectrometer is presented. A mixture of protein A, staphylococcal enterotoxin B and cytochrome c was used as a model mixture injected on a gel filtration column and a trypsin reactor which were connected in series to a micro liquid chromatography (mu LC) system. The peptides in the column eluate were analyzed with ESI tandem mass spectrometry, utilizing information dependent acquisition (IDA). In one step, the proteins in the mixture (mu M concentrations) were concomitantly desalted, separated, digested and identified with an overall analysis time of less than 40 min. Protein sequence coverage of 78-95% for the involved substances was achieved. (c) 2005 Elsevier B.V. All rights reserved.
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| 46. |
- Hedström, Martin, et al.
(author)
-
Miniaturized on-line digestion system for the sequential identification and characterization of protein analytes
- 2007
-
In: Journal of Chromatography A. - : Elsevier BV. - 0021-9673. ; 1146:1, s. 17-22
-
Journal article (peer-reviewed)abstract
- A miniaturized on-column digestion system constructed for the sequential analysis of semi-purified protein analytes is presented. By utilizing fused silica capillary (diameter 150 mu m) packed with a zone of trypsin-modified Eupergit C beads and a second zone of reversed-phase C18 material, a linear column set-up was constructed. The protein analytes (pmol amounts) were first digested in the 600 nl trypsin reactor portion of the system. Next, the generated peptides were trapped in the C18 column shaped as an electrospray emitter. Finally, after washing the matrix free from salts and other hydrophilic impurities present in the sample, peptides were eluted. A stepwise increased concentration profile of organic solvent, created by a dual syringe pump system, promoted the release of bound peptides, which were identified by electrospray ionization MS/MS. This approach proved to be very efficient, achieving almost complete digestion of the proteins studied, with suitable operational stability maintained for more than 1 week. Further, a small nebulizer was designed and fitted to the electrospray emitter. A significant improvement of the spray stability was observed and droplet build-up on the capillary was avoided, even at flow rates well above 1500 nl/min. The proteins chloroperoxidase, staphylococcal enterotoxin B and protein A (injection volume 0.3 mu l, salt concentration 0.2-1 M) were sequentially digested, desalted, eluted, detected and conclusively identified by bioinformatics web tools with an analytical cycle time of 10 min.
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| 47. |
- Hedström, Martin, et al.
(author)
-
Monolithic macroporous albumin/chitosan cryogel structure: a new matrix for enzyme immobilization.
- 2008
-
In: Analytical and Bioanalytical Chemistry. - : Springer Science and Business Media LLC. - 1618-2642 .- 1618-2650. ; 390:3, s. 907-912
-
Journal article (peer-reviewed)abstract
- A novel monolithic macroporous material was developed by cross-linking hen egg albumin (HEA) and chitosan with glutaraldehyde at subzero temperatures. A macroporous cryogel structure allowed efficient mass transport of solutes within the material. In one application, albumin was partially replaced with active enzymes (glucose oxidase and horseradish peroxidase) resulting in the production of macroporous biocatalyst preparations suitable for flow-injection analysis of glucose in the low millimolar range. In another application, the proteolytic enzymes savinase and esperase were coupled to the macroporous structure via free amino groups on the pore walls using glutaraldehyde as cross-linker/spacer agent. The low hydraulic resistance of the matrix allowed for the development of a generic, high-performance online protein digestion system utilizing the wall-bound proteases.
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| 48. |
- Hedström, Martin
(author)
-
Process Analytical Tools for the Monitoring and Characterization of Bacterial Toxins
- 2006
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Doctoral thesis (other academic/artistic)abstract
- In the era of proteomics, glycomics and ultimately metabolomics, with constantly increasing knowledge regarding the human biosystem, the number of specialized therapeutic agents which will be developed against different diseases is predicted to be on the upswing. An increasing portion of these new drugs will, according to recent predictions (Labrou, 2003), be of proteinaceous origin produced according to biotechnological standards. Hence, down stream processes (DSP) in which large amounts of specific target proteins are to be processed and purified, with high demands on process monitoring and control, will be of further increasing importance in the future. In the light of these predictions, the U.S. Food and Drug Administration (FDA) has proposed a set of new initiatives that primarily address the development of process analytical technology (PAT) as a concept within pharmaceutical manufacturing. The idea with PAT is to stimulate creative strategies for improved process developments, which in the end should lead to increased productivity concomitantly with the assurance of acceptable end-product quality (U.S. FDA, 2002). The definition of PAT involves the use of an overall process optimisation strategy applied at all production levels. Hence, the utilization of advanced bioprocess monitoring tools, which could lead to reduced production cycle times and prevention of rejects, scrap, and the need for re-processing, is covered in the description. A recent tendency within bioproduction monitoring is the shift in focus from the target molecule itself towards an increased control of the impurities present (World Health Organization, 1999). Among the relevant contaminants typically present in a bioproduction process, bacterial toxins have received high priority from the regulatory agencies (Ecker et al., 2005). In fact, a clear analytical strategy for the control of e.g. bacterial endotoxins is a necessity for the recombinant production of any FDA-approved pharmaceutically active proteinaceous agent (U.S. FDA, 1985). Currently, the only available method for endotoxin detection is the limulus amebocyte lysate (LAL) assay which is based on the Limulus lectin derived from the American horseshoe crab,. The LAL assay is expensive and time-consuming. Moreover, it is non-functional for the detection of endotoxins in trace amounts. Hence, the development of new, less labour-intensive methods with high sensitivity and specificity for the direct detection of endotoxins is highly desirable. Another important category of contaminants associated with biotechnological production comprises the exotoxins. This class of bacterial toxins typically includes soluble proteinaceous compounds, continually released by living bacteria. Extreme toxicities together with a typical ability to retain high activity under harsh conditions and in dilute solutions make exotoxins exceptionally competent as poisons, often with high mortality rates. The treatment of toxic by-products in biotechnological production is strictly regulated and the strategies for the removal of toxins associated with the product are often complex and completely dependant on the product application. A parallel situation is the handling of waste liquids remaining from the process. Fermentation of cell strains, capable of excreting exotoxic compounds to the surroundings, will consequently give waste liquids that require detoxification before being discarded. Hence, cost-effective methods for performing such tasks could be of interest to the manufacturer as e.g. the cost of sending the material for incineration could be a heavy toll on the profit margins. The objective in this thesis work was to investigate different means to analyze, characterize and process selected toxins of bacterial origin related to biotechnological production. With a vast array of compounds falling into the category of bacterial toxins, two different types were chosen; staphylococcal enterotoxin B (SEB), a 23 kDa exotoxin produced by Staphylococcus aureus and the heterogeneous group of endotoxins derived from the outer cell-wall of the gram-negative bacteria Escherichia coli.
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- Hedström, Ulf, et al.
(author)
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Impaired differentiation of chronic obstructive pulmonary disease bronchial epithelial cells grown on bronchial scaffolds
- 2021
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In: American Journal of Respiratory Cell and Molecular Biology. - 1044-1549. ; 65:2, s. 201-213
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Journal article (peer-reviewed)abstract
- Chronic obstructive pulmonary disease (COPD) is characterized by airway inflammation, small airway remodeling, and emphysema. Airway remodeling in patients with COPD involves both the airway epithelium and the subepithelial extracellular matrix (ECM). However, it is currently unknown how epithelial remodeling in COPD airways depends on the relative influence from inherent defects in the epithelial cells and alterations in the ECM. To address this, we analyzed global gene expression in COPD human bronchial epithelial cells (HBEC) and normal HBEC after repopulation on decellularized bronchial scaffolds derived from patients with COPD or donors without COPD. COPD HBEC grown on bronchial scaffolds showed an impaired ability to initiate ciliated-cell differentiation, which was evident on all scaffolds regardless of their origin. In addition, although normal HBEC were less affected by the disease state of the bronchial scaffolds, COPD HBEC showed a gene expression pattern indicating increased proliferation and a retained basal-cell phenotype when grown on COPD bronchial scaffolds compared with normal bronchial scaffolds. By using mass spectrometry, we identified 13 matrisome proteins as being differentially abundant between COPD bronchial scaffolds and normal bronchial scaffolds. These observations are consistent with COPD pathology and suggest that both epithelial cells and the ECM contribute to epithelial-cell remodeling in COPD airways.
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