| 83281. |
- Krassioukov, Andrei V, et al.
(författare)
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Assessment of autonomic dysfunction following spinal cord injury: rationale for additions to International Standards for Neurological Assessment.
- 2007
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Ingår i: Journal of rehabilitation research and development. - 0748-7711. ; 44:1, s. 103-12
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Tidskriftsartikel (refereegranskat)abstract
- We present a preliminary report of the discussion of the joint committee of the American Spinal Injury Association (ASIA) and the International Spinal Cord Society concerning the development of assessment criteria for general autonomic function testing following spinal cord injury (SCI). Elements of this report were presented at the 2005 annual meeting of the ASIA. To improve the evaluation of neurological function in individuals with SCI and therefore better assess the effects of therapeutic interventions in the future, we are proposing a comprehensive set of definitions of general autonomic nervous system dysfunction following SCI that should be assessed by clinicians. Presently the committee recommends the recognition and assessment of the following conditions: neurogenic shock, cardiac dysrhythmias, orthostatic hypotension, autonomic dysreflexia, temperature dysregulation, and hyperhidrosis.
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| 83282. |
- Krastins, B., et al.
(författare)
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Rapid development of sensitive, high-throughput, quantitative and highly selective mass spectrometric targeted immunoassays for clinically important proteins in human plasma and serum
- 2013
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Ingår i: Clinical Biochemistry. - : Elsevier BV. - 0009-9120. ; 46:6, s. 399-410
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Tidskriftsartikel (refereegranskat)abstract
- Objectives The aim of this study was to develop high-throughput, quantitative and highly selective mass spectrometric, targeted immunoassays for clinically important proteins in human plasma or serum. Design and methods The described method coupled mass spectrometric immunoassay (MSIA), a previously developed technique for immunoenrichment on a monolithic microcolumn activated with an anti-protein antibody and fixed in a pipette tip, to selected reaction monitoring (SRM) detection and accurate quantification of targeted peptides, including clinically relevant sequence or truncated variants. Results In this report, we demonstrate the rapid development of MSIA-SRM assays for sixteen different target proteins spanning seven different clinically important areas (including neurological, Alzheimer's, cardiovascular, endocrine function, cancer and other diseases) and ranging in concentration from pg/mL to mg/mL. The reported MSIA-SRM assays demonstrated high sensitivity (within published clinical ranges), precision, robustness and high-throughput as well as specific detection of clinically relevant isoforms for many of the target proteins. Most of the assays were tested with bona-fide clinical samples. In addition, positive correlations, (R2 0.67–0.87, depending on the target peptide), were demonstrated for MSIA-SRM assay data with clinical analyzer measurements of parathyroid hormone (PTH) and insulin growth factor 1 (IGF1) in clinical sample cohorts. Conclusions We have presented a practical and scalable method for rapid development and deployment of MS-based SRM assays for clinically relevant proteins and measured levels of the target analytes in bona fide clinical samples. The method permits the specific quantification of individual protein isoforms and addresses the difficult problem of protein heterogeneity in clinical proteomics applications.
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| 83283. |
- Krath, Jeanine, et al.
(författare)
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Does behaviour match user typologies? An exploratory cluster analysis of behavioural data from a gamified fitness platform.
- 2022
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Ingår i: CEUR Workshop Proceedings. - RWTH Aachen : CEUR Workshop. - 1613-0073. ; , s. 105-114
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Konferensbidrag (refereegranskat)abstract
- A promising solution to increase user engagement in gamified applications is tailored gamification design. However, current personalisation relies primarily on user types identified through self-reporting rather than actual behaviour. As a novel approach, the present study used an exploratory machine learning analysis to identify seven clusters of users in a gamified fitness application based on their behavioural data (N = 19,576). The clusters were then conceptually compared to common user typologies in gamification, identifying possible relationships between behavioural user clusters and user types motivated by achievement, sociability, and extrinsic incentives. The findings shed light on nuanced behaviour patterns of user types in the fitness context and how knowing these patterns can inform the way in which tailored gamification could be implemented to meet the needs of specific types. Thereby, they contribute to the discussion on utilising behavioural data and user typologies for tailored gamification design.
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| 83284. |
- Kratzat, Susanne, et al.
(författare)
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Cks1 is required for tumor cell proliferation but not sufficient to induce hematopoietic malignancies.
- 2012
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 7:5
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Tidskriftsartikel (refereegranskat)abstract
- The Cks1 component of the SCF(Skp2) complex is necessary for p27(Kip1) ubiquitylation and degradation. Cks1 expression is elevated in various B cell malignancies including Burkitt lymphoma and multiple myeloma. We have previously shown that loss of Cks1 results in elevated p27(Kip1) levels and delayed tumor development in a mouse model of Myc-induced B cell lymphoma. Surprisingly, loss of Skp2 in the same mouse model also resulted in elevated p27(Kip1) levels but exhibited no impact on tumor onset. This raises the possibility that Cks1 could have other oncogenic activities than suppressing p27(Kip1). To challenge this notion we have targeted overexpression of Cks1 to B cells using a conditional retroviral bone marrow transduction-transplantation system. Despite potent ectopic overexpression, Cks1 was unable to promote B cell hyperproliferation or B cell malignancies, indicating that Cks1 is not oncogenic when overexpressed in B cells. Since Skp2 overexpression can drive T-cell tumorigenesis or other cancers we also widened the quest for oncogenic activity of Cks1 by ubiquitously expressing Cks1 in hematopoetic progenitors. At variance with c-Myc overexpression, which caused acute myeloid leukemia, Cks1 overexpression did not induce myeloproliferation or leukemia. Therefore, despite being associated with a poor prognosis in various malignancies, sole Cks1 expression is insufficient to induce lymphoma or a myeloproliferative disease in vivo.
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| 83285. |
- Kratzer, I., et al.
(författare)
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The molecular anatomy and functions of the choroid plexus in healthy and diseased brain
- 2020
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Ingår i: Biochimica et Biophysica Acta - Biomembranes. - : Elsevier BV. - 0005-2736. ; 1862:11
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Tidskriftsartikel (refereegranskat)abstract
- The choroid plexus (CP) is located in the ventricular system of the brain (one in each ventricle), and the CP epithelial cells form an important barrier between the blood and the cerebrospinal fluid (CSF). Their main function comprises CSF secretion, maintenance of brain homeostasis, signalling, and forming a neuroprotective barrier against harmful external and internal compounds. The CPs mature early and demonstrate expressional changes of barrier-specific genes and proteins related to location and developmental stage of the CP. Important proteins for the barrier function include tight junction proteins, numerous transporters and enzymes. Natural senescence leads to structural changes in the CP cells and reduced or loss of function, while further loss of CP function and changes in immune status may be relevant in neurodegenerative diseases such as Alzheimer's disease and Multiple Sclerosis. Neuroprotective genes expressed at CPs may be unexplored targets for new therapies for neurodegenerative diseases. © 2020
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| 83286. |
- Kraupner, Nadine, et al.
(författare)
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Evidence for selection of multi-resistant E. coli by hospital effluent.
- 2021
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Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 150, s. 106436-
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Tidskriftsartikel (refereegranskat)abstract
- There is a risk that residues of antibiotics and other antimicrobials in hospital and municipal wastewaters could select for resistant bacteria. Still, direct experimental evidence for selection is lacking. Here, we investigated if effluent from a large Swedish hospital, as well as influent and effluent from the connected municipal wastewater treatment plant (WWTP) select for antibiotic resistant Escherichia coli in three controlled experimental setups. Exposure of sterile-filtered hospital effluent to a planktonic mix of 149 different E. coli wastewater isolates showed a strong selection of multi-resistant strains. Accordingly, exposure to a complex wastewater community selected for strains resistant to several antibiotic classes. Exposing individual strains with variable resistance patterns revealed a rapid bactericidal effect of hospital effluent on susceptible, but not multi-resistant E. coli. No selection was observed after exposure to WWTP effluent, while exposure to WWTP influent indicated a small selective effect for ceftazidime and cefadroxil resistant strains, and only in the E. coli mix assay. An analysis of commonly used antibiotics and non-antibiotic pharmaceuticals in combination with growth and resistance pattern of individual E. coli isolates suggested a possible contribution of ciprofloxacin and β-lactams to the selection by hospital effluent. However, more research is needed to clarify the contribution from different selective agents. While this study does not indicate selection by the studied WWTP effluent, there is some indications of selective effects by municipal influent on β-lactam-resistant strains. Such effects may be more pronounced in countries with higher antibiotic use than Sweden. Despite the limited antibiotic use in Sweden, the hospital effluent strongly and consistently selected for multi-resistance, indicating widespread risks. Hence, there is an urgent need for further evaluation of risks for resistance selection in hospital sewers, as well as for strategies to remove selective agents and resistant bacteria.
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| 83287. |
- Kraupner, Nadine, et al.
(författare)
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Selective concentration for ciprofloxacin resistance in Escherichia coli grown in complex aquatic bacterial biofilms
- 2018
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Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 116, s. 255-268
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Tidskriftsartikel (refereegranskat)abstract
- There is concern that antibiotics in the environment can select for and enrich bacteria carrying acquired antibiotic resistance genes, thus increasing the potential of those genes to emerge in a clinical context. A critical question for understanding and managing such risks is what levels of antibiotics are needed to select for resistance in complex bacterial communities. Here, we address this question by examining the phenotypic and genotypic profiles of aquatic communities exposed to ciprofloxacin, also evaluating the within-species selection of resistant E. coli in complex communities. The taxonomic composition was significantly altered at ciprofloxacin exposure concentrations down to 1 μg/L. Shotgun metagenomic analysis indicated that mobile quinolone resistance determinants (qnrD, qnrS and qnrB) were enriched as a direct consequence of ciprofloxacin exposure from 1 μg/L or higher. Only at 5–10 μg/L resistant E.coli increased relative to their sensitive counterparts. These resistant E. coli predominantly harbored non-transferrable, chromosomal triple mutations (gyrA S83 L, D87N and parC S80I), which confer high-level resistance. In a controlled experimental setup such as this, we interpret effects on taxonomic composition and enrichment of mobile quinolone resistance genes as relevant indicators of risk. Hence, the lowest observed effect concentration for resistance selection in complex communities by ciprofloxacin was 1 μg/L and the corresponding no observed effect concentration 0.1 μg/L. These findings can be used to define and implement discharge or surface water limits to reduce risks for selection of antibiotic resistance in the environment. © 2018 Elsevier Ltd
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| 83288. |
- Kraupner, Nadine, et al.
(författare)
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Selective concentrations for trimethoprim resistance in aquatic environments
- 2020
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Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 144
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Tidskriftsartikel (refereegranskat)abstract
- Antibiotic resistance presents a serious and still growing threat to human health. Environmental exposure levels required to select for resistance are unknown for most antibiotics. Here, we evaluated different experimental approaches and ways to interpret effect measures, in order to identify what concentration of trimethoprim that are likely to select for resistance in aquatic environments. When grown in complex biofilms, selection for resistant E. coli increased at 100 mu g/L, whereas there was only a non-significant trend with regards to changes in taxonomic composition within the tested range (0-100 mu g/L). Planktonic co-culturing of 149 different E. coli strains isolated from sewage again confirmed selection at 100 mu g/L. Finally, pairwise competition experiments were performed with engineered E. coli strains carrying different trimethoprim resistance genes (dfr) and their sensitive counterparts. While strains with introduced resistance genes grew slower than the sensitive ones at 0 and 10 mu g/L, a significant reduction in cost was found already at 10 mu g/L. Defining lowest effect concentrations by comparing proportion of resistant strains to sensitive ones at the same time point, rather than to their initial ratios, will reflect the advantage a resistance factor can bring, while ignoring exposure-independent fitness costs. As costs are likely to be highly dependent on the specific environmental and genetic contexts, the former approach might be more suitable as a basis for defining exposure limits with the intention to prevent selection for resistance. Based on the present and other studies, we propose that 1 mu g/L would be a reasonably protective exposure limit for trimethoprim in aquatic environments.
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| 83289. |
- Krause, Christian, et al.
(författare)
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Implementing graph transformations in the bulk synchronous parallel model
- 2014
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Ingår i: Fundamental Approaches to Software Engineering. 17th International Conference on Fundamental Approaches to Software Engineering (FASE), June 7-10, Grenoble, France. - Berlin, Heidelberg : Springer Berlin Heidelberg. - 0302-9743 .- 1611-3349. - 9783642548031 ; , s. 325-339
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Konferensbidrag (refereegranskat)abstract
- Big data becomes a challenge in more and more domains. In many areas, such as in social networks, the entities of interest have relational references to each other and thereby form large-scale graphs (in the order of billions of vertices). At the same time, querying and updating these data structures is a key requirement. Complex queries and updates demand expressive high-level languages which can still be efficiently executed on these large-scale graphs. In this paper, we use the well-studied concepts of graph transformation rules and units as a high-level modeling language with declarative and operational features for transforming graph structures. In order to apply them to large-scale graphs, we introduce an approach to distribute and parallelize graph transformations by mapping them to the Bulk Synchronous Parallel (BSP) model. Our tool support builds on Henshin as modeling tool and consists of a code generator for the BSP framework Apache Giraph. We evaluated the approach with the IMDB movie database and a computation cluster with up to 48 processing nodes with 8 cores each.
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| 83290. |
- Krause, Dino, et al.
(författare)
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Why Is There So Little Shia-Sunni Dialogue? : Understanding the Deficit of Intra-Muslim Dialogue and Interreligious Peacemaking
- 2019
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Ingår i: Religions. - : MDPI AG. - 2077-1444. ; 10:10
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Tidskriftsartikel (refereegranskat)abstract
- Despite a growth in fatalities resulting from organized violence with Shia-Sunni dimensions over the last two decades, in this study, we show, using existing data-bases on interreligious dialogue and peacemaking, that only less than two percent of the interreligious peacemaking organizations in the world are specialized in dialogue between Shias and Sunnis. Why is there so little institutionalized Shia-Sunni dialogue occurring when the need for such dialogue is evident? This study identifies and discusses this lack of institutional initiatives designed to prevent violence, manage conflicts and facilitate processes of intra-Muslim de-sectarianization. We discuss what we see as the three seemingly most obvious explanations-(1) the dismissal of the relevance of a Shia-Sunni cleavage, (2) the inappropriateness of the interreligious dialogue concept in the Muslim context, and (3) the substitution of institutional interreligious dialogue by other channels. Although we suggest that the third is the most potent explanation to pursue, we do not aim to provide a comprehensive explanation for the Shia-Sunni religious dialogue deficit. Instead, our aspiration is mainly to present and substantiate a puzzle that has not been identified or discussed in previous research. This can set an agenda for a reinvigorated research endeavor into the contemporary challenges for interreligious peacemaking.
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