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| 2. |
- Soukup, Ondrej, et al.
(author)
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Acetylcholinesterase inhibitors and drugs acting on muscarinic receptors - potential crosstalk of cholinergic mechanisms during pharmacological treatment.
- 2017
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In: Current neuropharmacology. - 1875-6190. ; 15:4, s. 637-653
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Journal article (peer-reviewed)abstract
- Pharmaceuticals with targets in the cholinergic transmission have been used for decades and are still fundamental treatments in many diseases and conditions today. Both the transmission and the effects of the somatomotoric and the parasympathetic nervous systems may be targeted by such treatments. Irrespective of the knowledge that the effects of neuronal signalling in the nervous systems may include a number of different receptor subtypes of both the nicotinic and the muscarinic receptors, this complexity is generally overlooked when assessing the mechanisms of action of pharmaceuticals. Presently, the life cycle of acetylcholine, muscarinic receptors and their effects are reviewed in the major organ systems of the body. Neuronal and non-neuronal sources of acetylcholine are elucidated. Examples of pharmaceuticals, in particular cholinesterase inhibitors, affecting these systems are discussed. The review focuses on salivary glands, the respiratory tract and the lower urinary tract, since the complexity of the interplay of different muscarinic receptor subtypes is of significance for physiological, pharmacological and toxicological effects in these organs.
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| 3. |
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Mat och krig
- 2012
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Editorial collection (pop. science, debate, etc.)
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| 4. |
- Jiang, Tao
(author)
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Underestimation of phosphorus fraction change in the supernatant after phosphorus adsorption onto iron oxides and iron oxide-natural organic matter complexes
- 2017
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In: Journal of Environmental Sciences. - : Elsevier BV. - 1001-0742. ; 55, s. 197-205
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Journal article (peer-reviewed)abstract
- The phosphorus (P) fraction distribution and formation mechanism in the supematant after P adsorption onto iron oxides and iron oxide-humic acid (HA) complexes were analyzed using the ultrafiltration method in this study. With an initial P concentration of 20 mg/L (I = 0.01 mol/L and pH = 7), it was shown that the colloid (1 kDa-0.45 gm) component of P accounted for 10.6%, 11.6%, 6.5%, and 4.0% of remaining total P concentration in the supematant after P adsorption onto ferrihydrite (FH), goethite (GE), ferrihydrite-humic acid complex (FH-HA), goethite-humic acid complex (GE-HA), respectively. The <1 kDa component of P was still the predominant fraction in the supematant, and underestimated colloidal P accounted for 2.2%, 55.1%, 45.5%, and 38.7% of P adsorption onto the solid surface of FH, FH-HA, GE and GE-HA, respectively. Thus, the colloid P could not be neglected. Notably, it could be interpreted that Fe3+ hydrolysis from the adsorbents followed by the formation of colloidal hydrous ferric oxide aggregates was the main mechanism for the formation of the colloid P in the supematant. And colloidal adsorbent particles co-existing in the supernatant were another important reason for it. Additionally, dissolve organic matter dissolved from iron oxide-HA complexes could occupy large adsorption sites of colloidal iron causing less colloid P in the supematant. Ultimately, we believe that the findings can provide a new way to deeply interpret the geochemical cycling of P, even when considering other contaminants such as organic pollutants, heavy metal ions, and arsenate at the sediment/soil-water interface in the real environment. (C) 2016 The Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences. Published by Elsevier B.V.
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| 5. |
- Schultz, Sebastian, et al.
(author)
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Drosophila Melanogaster as a Model System for Studies of Islet Amyloid Polypeptide Aggregation
- 2011
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:6
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Journal article (peer-reviewed)abstract
- Background: Recent research supports that aggregation of islet amyloid polypeptide (IAPP) leads to cell death and this makes islet amyloid a plausible cause for the reduction of beta cell mass, demonstrated in patients with type 2 diabetes. IAPP is produced by the beta cells as a prohormone, and proIAPP is processed into IAPP by the prohormone convertases PC1/3 and PC2 in the secretory granules. Little is known about the pathogenesis for islet amyloid and which intracellular mechanisms are involved in amyloidogenesis and induction of cell death.Methodology/Principal Findings: We have established expression of human proIAPP (hproIAPP), human IAPP (hIAPP) and the non-amyloidogenic mouse IAPP (mIAPP) in Drosophila melanogaster, and compared survival of flies with the expression driven to different cell populations. Only flies expressing hproIAPP in neurons driven by the Gal4 driver elavC(155,Gal4) showed a reduction in lifespan whereas neither expression of hIAPP or mIAPP influenced survival. Both hIAPP and hproIAPP expression caused formation of aggregates in CNS and fat body region, and these aggregates were both stained by the dyes Congo red and pFTAA, both known to detect amyloid. Also, the morphology of the highly organized protein granules that developed in the fat body of the head in hIAPP and hproIAPP expressing flies was characterized, and determined to consist of 15.8 nm thick pentagonal rod-like structures.Conclusions/Significance: These findings point to a potential for Drosophila melanogaster to serve as a model system for studies of hproIAPP and hIAPP expression with subsequent aggregation and developed pathology.
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| 6. |
- Schultz, Sebastian, et al.
(author)
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Fly model of type 2 diabetes: processing of proIAPP makes a difference
- 2010
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In: Amyloid. - : Informa Healthcare. - 1350-6129 .- 1744-2818. ; 17:S1, s. 44-45
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Journal article (other academic/artistic)abstract
- Patients with type 2 diabetes have a marked reducedbeta cell mass and fail to produce sufficient amounts of insulin required for regulation of glucose home- ostasis. Recent research supports that intracellular aggregation of islet amyloid polypeptide (IAPP) leads to cell death and therefore makes IAPP aggregation a plausible cause for the beta cell reduction. Little is known about the mechanisms that precede amyloid formation or which cellular pathways are involved in this process. To gain better understanding we haveestablished a Drosophila melanogaster model, where GAL4 drives expression of UAS-targeted transgenes in a cell or tissue specific pattern. The fruit fly offers a unique option to manipulate any cellular pathway with different genetic tools. The knowledge that*70% of all Drosophila melanogaster genes have anorthologue in humans stress the potential for path- ways found in D. melanogaster to be of importance in humans as well. Transgenic flies expressing human proIAPP (the precursor of IAPP) and IAPP and the non-amyloidogenic mouse IAPP (mIAPP) have been generated. Expression of proIAPP in the brain reduced the lifespan of the fly whereas neither IAPP nor mIAPP expression influenced survival. Immu- nolabelling with an antibody raised against human IAPP and that cross-reacts with murine IAPP labelled neurons in all three strains, whereas a concomitant loss of cell nuclei only appeared during proIAPP and IAPP expression. Furthermore, we detected an early potentiated activation of the autophagy pathway in proIAPP flies. Interestingly, even though IAPP expression was not related to a shorter lifespan, both IAPP and proIAPP expression in the central nervous system led to amyloid deposition in the fat body of the head as shown with Congo red and pFTAA, a newly synthesised luminescent conjugated polymer. Our results de- monstrate that D. melanogaster has a great potential as a model for studies of proIAPP and IAPP expression with subsequent amyloid formation and connected cellular response mechanisms. The find- ing that proIAPP aggregation seems to exert a more toxic impact at a cellular level is in line with ourresults from mammalian cell lines.
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| 7. |
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| 8. |
- Gurung, Ram B., et al.
(author)
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Learning Random Forest from Histogram Data Using Split Specific Axis Rotation
- 2018
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In: International Journal of Machine Learning and Computing. - : EJournal Publishing. - 2010-3700. ; 8:1, s. 74-79
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Journal article (peer-reviewed)abstract
- Machine learning algorithms for data containing histogram variables have not been explored to any major extent. In this paper, an adapted version of the random forest algorithm is proposed to handle variables of this type, assuming identical structure of the histograms across observations, i.e., the histograms for a variable all use the same number and width of the bins. The standard approach of representing bins as separate variables, may lead to that the learning algorithm overlooks the underlying dependencies. In contrast, the proposed algorithm handles each histogram as a unit. When performing split evaluation of a histogram variable during tree growth, a sliding window of fixed size is employed by the proposed algorithm to constrain the sets of bins that are considered together. A small number of all possible set of bins are randomly selected and principal component analysis (PCA) is applied locally on all examples in a node. Split evaluation is then performed on each principal component. Results from applying the algorithm to both synthetic and real world data are presented, showing that the proposed algorithm outperforms the standard approach of using random forests together with bins represented as separate variables, with respect to both AUC and accuracy. In addition to introducing the new algorithm, we elaborate on how real world data for predicting NOx sensor failure in heavy duty trucks was prepared, demonstrating that predictive performance can be further improved by adding variables that represent changes of the histograms over time.
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| 9. |
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| 10. |
- Lourdudoss, Sebastian, 1953-, et al.
(author)
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Preface
- 2018
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In: Semiconductors and Semimetals. - : Academic Press Inc.. - 9780128150993 ; , s. ix-xi
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Book chapter (peer-reviewed)
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