23 research outputs found
Secretion of celiac disease autoantibodies after in vitro gliadin challenge is dependent on small-bowel mucosal transglutaminase 2-specific IgA deposits
No full textBackground: In celiac disease gluten, the disease-inducing toxic component in wheat, induces the secretion of autoantibodies which are targeted against transglutaminase 2 (TG2). These autoantibodies are produced in the small-intestinal mucosa, where they can be found deposited extracellularly below the epithelial basement membrane and around mucosal blood vessels. In addition, during gluten consumption these autoantibodies can also be detected in patients' serum but disappear from the circulation on a gluten-free diet. Interestingly, after adoption of a gluten-free diet the serum autoantibodies disappear from the circulation more rapidly than the small-intestinal mucosal autoantibody deposits. The toxicity of gluten and the secretion of the disease-specific autoantibodies have been widely studied in organ culture of small-intestinal biopsy samples, but results hitherto have been contradictory. Since the mucosal autoantibodies disappear slowly after a gluten-free diet, our aim was to establish whether autoantibody secretion to organ culture supernatants in treated celiac disease patient biopsies is related to the duration of the diet and further to the preexistence of mucosal TG2-specific IgA deposits in the cultured biopsy samples.
Results: In the organ culture system conducted with biopsies derived from treated celiac disease patients, gliadin induced secretion of autoantibodies to culture supernatants, reduced epithelial cell height and increased the density of lamina proprial CD25+ cells. However, these changes could be demonstrated only in biopsies from short-term treated celiac disease patients, where the small-intestinal mucosal TG2-specific IgA autoantibody deposits were still present. Furthermore, in these biopsies autoantibody secretion could be stimulated fully only after a 48-hour gliadin challenge.
Conclusion: Our results show that studies focusing on the toxic effects of gliadin in the organ culture system should be carried out with biopsy samples from short-term treated celiac disease patients who are likely still to have mucosal IgA deposits present. In addition to providing an explanation for the discrepancies in previous publications, the present study also enables further validation of the organ culture method
Fuzzycat [Elektronisk resurs] : A Fuzzy Control Analysis Tool for Maple
No full textThis report is an abbreviated translation of a M.Sc thesis work about fuzzy control that was carried out by the second author (A.S.) under the supervision of the first author (K.F.) during the fall of 1992. The complete report (in Swedish) is [14]. Fuzzy Control is a design method for nonlinear controllers, which is becoming more and more common in industrial applications. However, a major disadvantage of fuzzy control, is that the controllers obtained are often difficult to analyze mathematically. Instead, much of the analysis so far has been made through simulation. In the thesis work a Maple software tool was developed, with which you could easily design and analyze fuzzy controllers. The tool makes it possible determine the closed expression for fuzzy control laws. It is then possible to analyze the closed loop system by standard methods from non-linear control theory (for example the circle criterion). It also has functions for translating the controller description to a MATLAB function (m-file), for example to be used in the MATLAB simulation environment, Simulink.FuzzyCAT is available by anonymous ftp at the address 130.236.24.1 (or equivalently joakim.isy.liu.se), contained in the file /pup/src/maple/FuzzyCAT/fuzzycat</p
Tumors of the adrenal glands : genetic and diagnostic aspects
No full textAdrenal tumors have varying clinical presentation, malignancy rates and patient morbidity. Adrenal cortical carcinomas (ACCs) are malignant tumors originating from the adrenal cortex. Pheochromocytomas (PCCs) arise from the adrenal medulla and abdominal Paragangliomas (PGLs), a highly related tumor type, arise in paraganglia mostly in the abdominal area. The genetic background of these tumors has been persistently studied, still knowledge is lacking regarding tumor development and genotype-phenotype relation.In Paper I, NF1 protein expression was investigated in an attempt to clarify a possible association between NF1 mutational status and immunohistochemical staining for NF1. The results showed absent NF1 immunoreactivity in most PCCs. A clear majority of the NF1 mutated cases showed no NF1 immunoreactivity, however that was also seen in the NF1 wild-type cases. From this study we conclude that immunohistochemistry is not an efficient screening tool to detect NF1 mutated cases in clinical practice. In Paper II and III, TERT promoter methylation densities were investigated in PPGLs and ACCs. Telomerase activation have been shown in these tumor types, however only some cases with telomerase activation could be explained by TERT promoter mutations. In PPGLs TERT promoter hypermethylation was found in metastatic PGLs. In ACCs hypermethylation of the TERT promoter region was found compared to normal adrenal samples and hypermethylation was associated with worse clinical outcome. Also, TERT copy number gain was observed in ACCs. We concluded that epigenetic alterations of TERT occur in PPGLs and ACCs and are associated with worse clinical outcome. In Paper IV, histological signs of malignant behavior and mRNA expressional profiles were compared in PPGLs. The results pointed out Chromogranin B (CHGB) as the gene most significantly associated to malignant histological patterns and downregulation of CHGB was found in PPGLs with metastatic disease. Immunohistochemistry showed that weak CHGB expression was associated with histologically malignant behavior. Also, plasma levels of CHGB were lower in PPGLs with histologically aggressive disease. We concluded that CHGB is a possible marker for malignant disease in PPGLs. In Paper V, analysis of whole-exome sequencing data from our cohort as well as from the TCGA database revealed several variants in the calcium voltage-gated channel subunit gene CACNA1H. A total of seven variants were detected in the study. CACNA1H expression was found to be lower in tumor tissue as compared to normal adrenal medulla. In the TCGA database a correlation was found between CACNA1H methylation levels and CACNA1H expression. We concluded that variants in CACNA1H are a possible novel genetic event in PPGL and also a possible link between the genetic background of PPGLs and tumors of the adrenal cortex where CACNA1H mutations have also been found. Overall this thesis gives some clarity to the knowledge gaps in the molecular background of tumors of the adrenal glands.List of scientific papersI. Immunohistochemical NF1 analysis does not predict NF1 gene mutation status in pheochromocytoma. Stenman A#, Svahn F#, Welander J, Gustavson B, Söderkvist P, Gimm O, Juhlin CC*. Endocrine Pathology. 2015 Mar;26(1):9-14. #Authors contributed equally, *Corresponding author. https://doi.org/10.1007/s12022-014-9348-1 II. Telomerase reverse transcriptase promoter hypermethylation is associated with metastatic disease in abdominal paraganglioma. Svahn F, Juhlin CC, Paulsson JO, Fotouhi O, Zedenius J, Larsson C, Stenman A*. Clinical Endocrinology. 2018 Feb;88(2):343-345. *Corresponding author. https://doi.org/10.1111/cen.13513 III. TERT promoter hypermethylation is associated with poor prognosis in adrenocortical carcinoma. Svahn F*, Paulsson JO, Stenman A*, Fotouhi O, Mu N, Murtha TD, Korah R, Carling T, Bäckdahl M, Wang N, Juhlin CC, Larsson C. International Journal of Molecular Medicine. 2018 Sep;42(3):1675-1683. *Corresponding author. https://doi.org/10.3892/ijmm.2018.3735 IV. Molecular profiling of pheochromocytoma and abdominal paraganglioma stratified by the PASS algorithm reveals chromogranin B as associated with histologic prediction of malignant behavior. Stenman A*, Svahn F, Hojjat-Farsangi M, Zedenius J, Söderkvist P, Gimm O, Larsson C#, Juhlin CC#. American Journal of Surgical Pathology. 2019 Mar;43(3):409-421. #Authors contributed equally, *Corresponding author. https://doi.org/10.1097/PAS.0000000000001190 V. Constitutional variants and tumor-specific down-regulation of the calcium voltage-gated channel subunit CACNA1H in pheochromocytoma. Svahn F, Stenman A, Calissendorff J, Tham E, Bränström R, Wang N, Korah R, Carling T, Zedenius J, Larsson C# and Juhlin CC#*. #Authors contributed equally, *Corresponding author. [Manuscript]</p
A Unified Model for Inter- and Intra-processor Concurrency
No full textAlthough concurrency is generally perceived to be a `hard' subject, it can in fact be very simple --- provided that the underlying model is simple. The occam-pi parallel processing language provides such a simple yet powerful concurrency model that is based on CSP and the pi-calculus. This thesis presents pony, the occam-pi Network Environment. occam-pi and pony provide a new, unified, concurrency model that bridges inter- and intra-processor concurrency. This enables the development of distributed applications in a transparent, dynamic and highly scalable way. The author specified the layout of the pony system as presented in this thesis, and carried out about 90% of the implementation. This thesis is structured into three main parts, as well as an introduction and an appendix. In the introduction, the need for a unified concurrency model is examined in detail. Thereupon, the pony environment is presented as a solution that provides such a unified model. The first part of this thesis is concerned with the usage of the pony environment for the development of distributed applications. It presents the interface between pony and the user-level code, as well as pony's configuration and a sample application. The second part presents the design and implementation of the pony environment. It explains the internal structure of pony, the implementation of pony's components and public processes, and the integration of pony in the KRoC compiler. The third part evaluates pony's performance and contains the final conclusions. It presents a number of performance tests and concludes with a discussion of the work presented in this thesis, along with an outline of possible future research
Frankia-enriched metagenomes from the earliest diverging symbiotic Frankia cluster: They come in teams.
No full textNguyen TV, Wibberg D, Vigil-Stenman T, et al. Frankia-enriched metagenomes from the earliest diverging symbiotic Frankia cluster: They come in teams. Genome biology and evolution. 2019;11(8):2273–2291.Frankia strains induce the formation of nitrogen-fixing nodules on roots of actinorhizal plants. Phylogenetically, Frankia strains can be grouped in four clusters. The earliest divergent cluster, cluster-2, has a particularly wide host range. The analysis of cluster-2 strains has been hampered by the fact that with two exceptions, they could never be cultured. In this study, 12 Frankia-enriched metagenomes of Frankia cluster-2 strains or strain assemblages were sequenced based on seven inoculum sources. Sequences obtained via DNA isolated from whole nodules were compared to those of DNA isolated from fractionated preparations enhanced in the Frankia symbiotic structures. The results show that cluster-2 inocula represent groups of strains, and that strains not represented in symbiotic structures, i.e., unable to perform symbiotic nitrogen fixation, may still be able to colonize nodules. Transposase gene abundance was compared in the different Frankia-enriched metagenomes with the result that North American strains contain more transposase genes than Eurasian strains. An analysis of the evolution and distribution of the host plants indicated that bursts of transposition may have coincided with niche competition with other cluster-2 Frankia strains. The first genome of an inoculum from the Southern Hemisphere, obtained from nodules of Coriaria papuana in Papua New Guinea, represents a novel species, postulated as Candidatus Frankia meridionalis. All Frankia-enriched metagenomes obtained in this study contained homologs of the canonical nod genes nodABC; the North American genomes also contained the sulfotransferase gene nodH, while the genome from the Southern Hemisphere only contained nodC and a truncated copy of nodB. © The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution
Estimating individual driving distance by car and public transport use in Sweden
No full textHow much to drive, and how much to use public transport, are modelled as three- and two level decisions, respectively, based on micro-data for Sweden. The choices whether to have a car, whether to drive given access to a car, and how much to drive given that the individual drives at all are then estimated using a three equation model. Also after correcting for other variables, such as income, men are driving much more, and using less public transport, compared to women. People living in big cities are less likely to drive, but those who do are on average driving about as much as others. Age and access to company-cars are also important determinants for travel behaviour, but being a member of an environmental organisation is not. Driving increases with income, but to a lower degree compared to most aggregated studies on national level. The difference is explained in a simple model with income-dependent structural changes, implying that it becomes more difficult to live without a car when average income increases. This indirect effect is found to be of a similar size as the ordinary income elasticity typically found in cross-section analysis within a country or region.Transport demand; car ownership; car use; driving; public transport demand; multi-level decisions; social context; gender and transport
Behavioral economics, neuroeconomics, and climate change policy: baseline review for the garrison institute initiative on climate change
No full textIn spite of the increasing scientific certainty that the earth's climate is warming and that human activity is partially responsible, public willingness to take steps to reduce greenhouse gas emissions seems to be decreasing. How can the scientific consensus as to the urgency of the climate change problem be conveyed to the general public in such a way as to support greenhouse gas abatement policies and to actually change behavior? This essay explores the standard economic approach to environmental pollution and discusses findings from behavioral economics and neuroscience that could lead to a more fruitful understanding of the relationship between economic policy and human psychology. This essay is a background paper prepared for the Garrison Institute's "Climate, Mind and Behavior" initiative.
Asymmetry of acetylcholinesterase and acetylcholine receptor in intact secretory vesicles from adrenal medulla
No full textA new modification of the chiron ACS assay for total prostate-specific antigen achieves equimolar response characteristics and improves the detection of prostate cancer
No full textNonequimolar-response assays for prostate-specific antigen (PSA) are criticized for overestimating total PSA in some men without prostate cancer (PCA), and underestimating total PSA in some men with PCA. We recently studied three nonequimolar-response PSA assays that had undergone modifications. While two of the studied assays achieved equimolar-response characteristics with improved areas under receiver operating characteristic (ROC) curves (AUC), the modification of the Chiron ACS PSA assay (ACS PSA2, Chiron) failed to achieve this. Recently, the ACS assay underwent another modification (ACS PSA, Bayer), which we investigated. Sera from 305 men (155 without and 150 with PCA, PSA greater than or equal to2 and less than or equal to30 mug/l, TandemE) were measured using both modifications of the ACS assay and equimolar-response reference methods (TandemR free and Tandem E, Hybritech). Molar response relative to the reference method and clinical performance (comparison of AUCs) between the previous and new ACS assay modifications were studied. The new modification of the ACS assay (ACS PSA, Bayer) achieved equimolar-response characteristics but reported lower values (average 10%) than the Tandem E assay. Compared to the previous modification (ACS PSA2, Chiron), a 3% improvement in AUC (p=0.01) was found. Using results of the redesigned equimolar-response assay (ACS PSA, Bayer), we calculated that 6 of 155 men without PCA in this sample set could be spared unnecessary biopsy compared with the previous nonequimolar-response assay (ACS PSA2, Chiron) without missing additional PCA (90% sensitivity). These data provide additional evidence for clinical advantages of equimolar-response over nonequimolar-response PSA assay formats
End-stage renal disease and survival in people with diabetes : a national database linkage study
No full text© The Author 2014. Published by Oxford University Press on behalf of the Association of Physicians. Funding This work was supported by the Wellcome Trust through the Scottish Health Informatics Programme (SHIP). The SHIP is collaboration between the Universities of Aberdeen, Dundee, Edinburgh, Glasgow and St Andrews and the Information Services Division of National Health Service National Service Scotland. Funding for diabetes register linkage and data extraction was provided by the Chief Scientist’s Office of the Scottish Government. The Scottish Diabetes Research Network receives financial support from National Health Services Research Scotland. The Scottish Renal Registry is funded by the Information Services Division of National Health Service National Services Scotland but relies heavily on the goodwill of the contributing renal units who spent a large amount time working with Scottish Renal Registry staff to ensure that the data held within the register are accurate and complete.Peer reviewe
