| 51. |
- Koller, Jan, et al.
(författare)
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Simulation-Based Analysis of (Reverse) Supply Chains in Circular Product-Service-Systems
- 2023
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Ingår i: Manufacturing Driving Circular Economy: Proceedings of the 18th Global Conference on Sustainable Manufacturing, October 5–7, 2022, Berlin. - Cham, Switzerland : Springer Nature Switzerland AG. - 2195-4364 .- 2195-4356. - 9783031288395 - 9783031288388 ; , s. 111-118
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Konferensbidrag (refereegranskat)abstract
- With an expected growth of global waste to 3.40 billion tonnes by 2050 and a circularity today of only 8.6% of the world, the earth's sustainable resources are being exploited beyond their regeneration capacity. Hence, it is necessary to step away from a take – make – dispose principal and transform from a linear towards a circular economy to close product cycles to optimize resource consumption and reduce waste. Product-Service-Systems (PSSs), based on multiple product life cycles combined with remanufacturing, offer a solution to close product cycles. In such PSS, the responsibility for returning, remanufacturing, and repairing used products remains with the Original Equipment Manufacturer (OEM) and increases its need in (reverse) supply chain activities. Essential factors for (reverse) supply chains are, e.g., determining the distribution network, the location of recovery facilities, the geographical dispersion of the customers, and the information flows between the different stakeholders. In this context, this work proposes a multi-method simulation model to support practitioners in determining the optimal infrastructure for storing, remanufacturing, and repairing the used products regarding economic and ecological target criteria. The applicability of the proposed approach is illustrated through a case study of a white goods manufacturing company. This case study highlights the importance of determining the optimal infrastructure in a (reverse) supply chain in PSS business models.
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| 52. |
- Koller, Timm O, et al.
(författare)
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Structural basis for HflXr-mediated antibiotic resistance in Listeria monocytogenes
- 2022
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Ingår i: Nucleic Acids Research. - : Oxford University Press (OUP). - 1362-4962 .- 0305-1048. ; 50:19, s. 11285-11300
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Tidskriftsartikel (refereegranskat)abstract
- HflX is a ubiquitous bacterial GTPase that splits and recycles stressed ribosomes. In addition to HflX, Listeria monocytogenes contains a second HflX homolog, HflXr. Unlike HflX, HflXr confers resistance to macrolide and lincosamide antibiotics by an experimentally unexplored mechanism. Here, we have determined cryo-EM structures of L. monocytogenes HflXr-50S and HflX-50S complexes as well as L. monocytogenes 70S ribosomes in the presence and absence of the lincosamide lincomycin. While the overall geometry of HflXr on the 50S subunit is similar to that of HflX, a loop within the N-terminal domain of HflXr, which is two amino acids longer than in HflX, reaches deeper into the peptidyltransferase center. Moreover, unlike HflX, the binding of HflXr induces conformational changes within adjacent rRNA nucleotides that would be incompatible with drug binding. These findings suggest that HflXr confers resistance using an allosteric ribosome protection mechanism, rather than by simply splitting and recycling antibiotic-stalled ribosomes.
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| 53. |
- Möller, Christian, et al.
(författare)
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Pollen immunotherapy reduces the development of asthma in children with seasonal rhinoconjunctivitis (the PAT-study)
- 2002
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Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 0091-6749 .- 1097-6825. ; 109:2, s. 251-256
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Tidskriftsartikel (refereegranskat)abstract
- Background: Children with allergic rhinitis are likely to develop asthma.Objective: The purpose of this investigation was to determine whether specific immunotherapy can prevent the development of asthma and reduce bronchial hyperresponsiveness in children with seasonal allergic rhinoconjunctivitis.Methods: From 6 pediatric allergy centers, 205 children aged 6 to 14 years (mean age, 10.7 years) with grass and/or birch pollen allergy but without any other clinically important allergy were randomized either to receive specific immunotherapy for 3 years or to an open control group. All subjects had moderate to severe hay fever symptoms, but at inclusion none reported asthma with need of daily treatment. Symptomatic treatment was limited to loratadine, levocabastine, sodium cromoglycate, and nasal budesonide. Asthma was evaluated clinically and by peak flow. Methacholine bronchial provocation tests were carried out during the season(s) and during the winter.Results: Before the start of immunotherapy, 20% of the children had mild asthma symptoms during the pollen season(s). Among those without asthma, the actively treated children had significantly fewer asthma symptoms after 3 years as evaluated by clinical diagnosis (odds ratio, 2.52; P < .05). Methacholine bronchial provocation test results improved significant in the active group (P < .05).Conclusion: Immunotherapy can reduce the development of asthma in children with seasonal rhinoconjunctivitis.
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| 54. |
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| 55. |
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| 56. |
- Robinson-Cohen, Cassianne, et al.
(författare)
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Genetic Variants Associated with Circulating Parathyroid Hormone.
- 2017
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Ingår i: Journal of the American Society of Nephrology : JASN. - 1533-3450. ; 28:5, s. 1553-1565
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Tidskriftsartikel (refereegranskat)abstract
- Parathyroid hormone (PTH) is a primary calcium regulatory hormone. Elevated serum PTH concentrations in primary and secondary hyperparathyroidism have been associated with bone disease, hypertension, and in some studies, cardiovascular mortality. Genetic causes of variation in circulating PTH concentrations are incompletely understood. We performed a genome-wide association study of serum PTH concentrations among 29,155 participants of European ancestry from 13 cohort studies (n=22,653 and n=6502 in discovery and replication analyses, respectively). We evaluated the association of single nucleotide polymorphisms (SNPs) with natural log-transformed PTH concentration adjusted for age, sex, season, study site, and principal components of ancestry. We discovered associations of SNPs from five independent regions with serum PTH concentration, including the strongest association with rs6127099 upstream of CYP24A1 (P=4.2 × 10(-53)), a gene that encodes the primary catabolic enzyme for 1,25-dihydroxyvitamin D and 25-dihydroxyvitamin D. Each additional copy of the minor allele at this SNP associated with 7% higher serum PTH concentration. The other SNPs associated with serum PTH concentration included rs4074995 within RGS14 (P=6.6 × 10(-17)), rs219779 adjacent to CLDN14 (P=3.5 × 10(-16)), rs4443100 near RTDR1 (P=8.7 × 10(-9)), and rs73186030 near CASR (P=4.8 × 10(-8)). Of these five SNPs, rs6127099, rs4074995, and rs219779 replicated. Thus, common genetic variants located near genes involved in vitamin D metabolism and calcium and renal phosphate transport associated with differences in circulating PTH concentrations. Future studies could identify the causal variants at these loci, and the clinical and functional relevance of these variants should be pursued.
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| 57. |
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| 58. |
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| 59. |
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| 60. |
- Toth, Peter, et al.
(författare)
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Traumatic brain injury-induced autoregulatory dysfunction and spreading depression-related neurovascular uncoupling : Pathomechanisms, perspectives, and therapeutic implications
- 2016
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Ingår i: American Journal of Physiology. - : HighWire Press. - 0002-9513 .- 2163-5773. ; 311:5, s. H1118-H1131
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Forskningsöversikt (refereegranskat)abstract
- Traumatic brain injury (TBI) is a major health problem worldwide. In addition to its high mortality (35-40%), survivors are left with cognitive, behavioral, and communicative disabilities. While little can be done to reverse initial primary brain damage caused by trauma, the secondary injury of cerebral tissue due to cerebro-microvascular alterations and dysregulation of cerebral blood flow (CBF) is potentially preventable. This review focuses on functional, cellular, and molecular changes of autoregulatory function of CBF (with special focus on cerebrovascular myogenic response) that occur in cerebral circulation after TBI and explores the links between autoregulatory dysfunction, impaired myogenic response, microvascular impairment, and the development of secondary brain damage. We further provide a synthesized translational view of molecular and cellular mechanisms involved in cortical spreading depolarization-related neurovascular dysfunction, which could be targeted for the prevention or amelioration of TBI-induced secondary brain damage.
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