| 1. |
- Ludvigsson, Jonas F., 1969-, et al.
(författare)
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Diagnosis and management of adult coeliac disease : guidelines from the British Society of Gastroenterology
- 2014
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Ingår i: Gut. - : BMJ Publishing Group Ltd. - 0017-5749 .- 1468-3288. ; 63:8, s. 1210-1228
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Tidskriftsartikel (refereegranskat)abstract
- A multidisciplinary panel of 18 physicians and 3 non-physicians from eight countries (Sweden, UK, Argentina, Australia, Italy, Finland, Norway and the USA) reviewed the literature on diagnosis and management of adult coeliac disease (CD). This paper presents the recommendations of the British Society of Gastroenterology. Areas of controversies were explored through phone meetings and web surveys. Nine working groups examined the following areas of CD diagnosis and management: classification of CD; genetics and immunology; diagnostics; serology and endoscopy; follow-up; gluten-free diet; refractory CD and malignancies; quality of life; novel treatments; patient support; and screening for CD.
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| 2. |
- Barbero-Palacios, Laura, et al.
(författare)
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Herbivore diversity effects on Arctic tundra ecosystems : a systematic review
- 2024
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Ingår i: Environmental Evidence. - : BioMed Central (BMC). - 2047-2382. ; 13:1
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Forskningsöversikt (refereegranskat)abstract
- Background: Northern ecosystems are strongly influenced by herbivores that differ in their impacts on the ecosystem. Yet the role of herbivore diversity in shaping the structure and functioning of tundra ecosystems has been overlooked. With climate and land-use changes causing rapid shifts in Arctic species assemblages, a better understanding of the consequences of herbivore diversity changes for tundra ecosystem functioning is urgently needed. This systematic review synthesizes available evidence on the effects of herbivore diversity on different processes, functions, and properties of tundra ecosystems.Methods: Following a published protocol, our systematic review combined primary field studies retrieved from bibliographic databases, search engines and specialist websites that compared tundra ecosystem responses to different levels of vertebrate and invertebrate herbivore diversity. We used the number of functional groups of herbivores (i.e., functional group richness) as a measure of the diversity of the herbivore assemblage. We screened titles, abstracts, and full texts of studies using pre-defined eligibility criteria. We critically appraised the validity of the studies, tested the influence of different moderators, and conducted sensitivity analyses. Quantitative synthesis (i.e., calculation of effect sizes) was performed for ecosystem responses reported by at least five articles and meta-regressions including the effects of potential modifiers for those reported by at least 10 articles.Review findings: The literature searches retrieved 5944 articles. After screening titles, abstracts, and full texts, 201 articles including 3713 studies (i.e., individual comparisons) were deemed relevant for the systematic review, with 2844 of these studies included in quantitative syntheses. The available evidence base on the effects of herbivore diversity on tundra ecosystems is concentrated around well-established research locations and focuses mainly on the impacts of vertebrate herbivores on vegetation. Overall, greater herbivore diversity led to increased abundance of feeding marks by herbivores and soil temperature, and to reduced total abundance of plants, graminoids, forbs, and litter, plant leaf size, plant height, and moss depth, but the effects of herbivore diversity were difficult to tease apart from those of excluding vertebrate herbivores. The effects of different functional groups of herbivores on graminoid and lichen abundance compensated each other, leading to no net effects when herbivore effects were combined. In turn, smaller herbivores and large-bodied herbivores only reduced plant height when occurring together but not when occurring separately. Greater herbivore diversity increased plant diversity in graminoid tundra but not in other habitat types.Conclusions: This systematic review underscores the importance of herbivore diversity in shaping the structure and function of Arctic ecosystems, with different functional groups of herbivores exerting additive or compensatory effects that can be modulated by environmental conditions. Still, many challenges remain to fully understand the complex impacts of herbivore diversity on tundra ecosystems. Future studies should explicitly address the role of herbivore diversity beyond presence-absence, targeting a broader range of ecosystem responses and explicitly including invertebrate herbivores. A better understanding of the role of herbivore diversity will enhance our ability to predict whether and where shifts in herbivore assemblages might mitigate or further amplify the impacts of environmental change on Arctic ecosystems.
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| 3. |
- Boza-Serrano, Antonio, et al.
(författare)
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Galectin-3, a novel endogenous TREM2 ligand, detrimentally regulates inflammatory response in Alzheimer’s disease
- 2019
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Ingår i: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 0001-6322 .- 1432-0533. ; 138:2, s. 251-273
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer’s disease (AD) is a progressive neurodegenerative disease in which the formation of extracellular aggregates of amyloid beta (Aβ) peptide, fibrillary tangles of intraneuronal tau and microglial activation are major pathological hallmarks. One of the key molecules involved in microglial activation is galectin-3 (gal3), and we demonstrate here for the first time a key role of gal3 in AD pathology. Gal3 was highly upregulated in the brains of AD patients and 5xFAD (familial Alzheimer’s disease) mice and found specifically expressed in microglia associated with Aβ plaques. Single-nucleotide polymorphisms in the LGALS3 gene, which encodes gal3, were associated with an increased risk of AD. Gal3 deletion in 5xFAD mice attenuated microglia-associated immune responses, particularly those associated with TLR and TREM2/DAP12 signaling. In vitro data revealed that gal3 was required to fully activate microglia in response to fibrillar Aβ. Gal3 deletion decreased the Aβ burden in 5xFAD mice and improved cognitive behavior. Interestingly, a single intrahippocampal injection of gal3 along with Aβ monomers in WT mice was sufficient to induce the formation of long-lasting (2 months) insoluble Aβ aggregates, which were absent when gal3 was lacking. High-resolution microscopy (stochastic optical reconstruction microscopy) demonstrated close colocalization of gal3 and TREM2 in microglial processes, and a direct interaction was shown by a fluorescence anisotropy assay involving the gal3 carbohydrate recognition domain. Furthermore, gal3 was shown to stimulate TREM2–DAP12 signaling in a reporter cell line. Overall, our data support the view that gal3 inhibition may be a potential pharmacological approach to counteract AD.
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| 4. |
- Carlsson, Susanne, et al.
(författare)
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Affinity of galectin-8 and its carbohydrate recognition domains for ligands in solution and at the cell surface.
- 2007
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Ingår i: Glycobiology. - : Oxford University Press (OUP). - 0959-6658 .- 1460-2423. ; 17:6, s. 663-76
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Tidskriftsartikel (refereegranskat)abstract
- Galectin-8 has two different carbohydrate recognition domains (CRDs), the N-terminal Gal-8N and the C-terminal Gal-8C linked by a peptide, and has various effects on cell adhesion and signaling. To understand the mechanism for these effects further, we compared the binding activities of galectin-8 in solution with its binding and activation of cells. We used glycan array analysis to broaden the specificity profile of the two galectin-8 CRDs, as well as intact galectin-8s (short and long linker), confirming the unique preference for sulfated and sialylated glycans of Gal-8N. Using a fluorescence anisotropy assay, we examined the solution affinities for a subset of these glycans, the highest being 50 nM for NeuAcalpha2,3Lac by Gal-8N. Thus, carbohydrate-protein interactions can be of high affinity without requiring multivalency. More importantly, using fluorescence polarization, we also gained information on how the affinity is built by multiple weak interactions between different fragments of the glycan and its carrier molecule and the galectin CRD subsites (A-E). In intact galectin-8 proteins, the two domains act independently of each other in solution, whereas at a surface they act together. Ligands with moderate or weak affinity for the isolated CRDs on the array are bound strongly by intact galectin-8s. Also galectin-8 binding and signaling at cell surfaces can be explained by combined binding of the two CRDs to low or medium affinity ligands, and their highest affinity ligands, such as sialylated galactosides, are not required.
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| 5. |
- Cebecauer, Matej, et al.
(författare)
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Integrating Demand Responsive Services into Public Transport Disruption Management
- 2021
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Ingår i: IEEE Open Journal of Intelligent Transportation Systems. - : Institute of Electrical and Electronics Engineers (IEEE). - 2687-7813. ; 2, s. 24-36
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Tidskriftsartikel (refereegranskat)abstract
- High-capacity public transport services such as metro and commuter trains are efficient during normal operations but are vulnerable to disruptions. To manage disruptions, bridging buses are commonly called in to replace the rail-based service along the disrupted lines. These often take significant time to arrive and are costly to keep stand-by. Demand-responsive transport such as taxi can respond to demand almost immediately but is costly and must usually be arranged by the individual travelers. This study examines the integration and potential role of demand-responsive transport in disruption management. The analysis considers the impacts of limiting the serving area, varying the number of available vehicles, pursuing ride-sharing, as well as a system-of-systems approach with collaboration between taxis and bridging buses. Results of computational experiments on the case study of Stockholm, Sweden reveal that integration of demand-responsive transport in the disruption management can bring large positive benefits in terms of average and maximum waiting times for travelers. This is especially the case for strategies including ridesharing. It is also shown that appropriate trade-offs between desired waiting times and costs can be achieved by collaboration of both bridging buses and demand-responsive transport. Additionally, more robust public transport with increased reliability during disruptions can increase sustainability as more people may choose public transport instead of private cars.
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| 6. |
- Cebecauer, Matej, et al.
(författare)
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Public transport disruption management by collaboration with demand responsive services
- 2020
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Konferensbidrag (refereegranskat)abstract
- For large cities, public transport represents the backbone for commuters and thus plays a crucial role for society and for the economy. High-capacity public transport services such as metro and commuter trains are efficient during normal operations but are vulnerable to disruptions. Metro and commuter train disruptions can be handled in several ways. Very common are bridging buses that are called in to replace the rail-based service along the disrupted lines. These often take significant time to arrive and are costly to keep stand-by. Demand-responsive transport such as taxi can respond to demand almost immediately but is costly and must usually be arranged by the individual travelers. This study examines the integration and potential role of demand-responsive transport in disruption management. The analysis considers the impacts of limiting the serving area, varying the number of available vehicles, pursuing ridesharing, as well as a system-of-systems approach with collaboration between taxis and bridging buses. Results of computational experiments on the case study of Stockholm, Sweden reveal that integration of demand-responsive transport in the disruption management can bring large positive benefits in terms of average and maximum waiting times for travelers. This is especially the case for strategies including ridesharing. It is also shown that appropriate trade-offs between desired waiting times and costs can be achieved by collaboration of both bridging buses and demand-responsive transport. Additionally, it is expected that more robust public transport with increased reliability during disruptions can increase sustainability as more people may choose public transport instead of private cars.
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| 7. |
- Gunnarsson, David, et al.
(författare)
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Mono-(2-ethylhexyl) phthalate stimulates basal steroidogenesis by a cAMP-independent mechanism in mouse gonadal cells of both sexes
- 2008
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Ingår i: Reproduction. - 1470-1626 .- 1476-3990. ; 135:5, s. 693-703
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Tidskriftsartikel (refereegranskat)abstract
- Phthalates are widely used as plasticizers in a number of daily-life products. In this study, we investigated the influence of mono-(2-ethylhexyl) phthalate (MEHP), the active metabolite of the frequently used plasticizer di-(2-ethylhexyl) phthalate (DEHP), on gonadal steroidogenesis in vitro. MEHP (25–100 µM) stimulated basal steroid synthesis in a concentration-dependent manner in immortalized mouse Leydig tumor cells (MLTC-1). The stimulatory effect was also detected in KK-1 granulosa tumor cells. MEHP exposure did not influence cAMP or StAR protein levels and induced a gene expression profile of key steroidogenic proteins different from the one induced by human chorionic gonadotropin (hCG). Simultaneous treatment with MEHP and a p450scc inhibitor (aminoglutethimide) indicated that MEHP exerts its main stimulatory effect prior to pregnenolone formation. MEHP (10–100 µM) up-regulated hormone-sensitive lipase and 3-hydroxy-3-methylglutaryl coenzyme A reductase, suggesting that MEHP increases the amount of cholesterol available for steroidogenesis. Our data suggest that MEHP, besides its known inhibitory effect on hCG action, can directly stimulate gonadal steroidogenesis in both sexes through a cAMP- and StAR-independent mechanism. The anti-steroidogenic effect of DEHP has been proposed to cause developmental disorders such as hypospadias and cryptorchidism, whereas a stimulation of steroid synthesis may prematurely initiate the onset of puberty and theoretically affect the hypothalamic–pituitary–gonadal axis.
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| 8. |
- Gunnarsson, David, 1975-
(författare)
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Reproductive toxicology of endocrine disruptors : effects of cadmium, phthalates and phytoestrogens on testicular steroidogenesis
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- A number of investigations during the last two decades describe adverse trends in male reproductive health, which have been proposed to be caused by environmental factors with endocrine disrupting properties. In contrast to many other toxicants, endocrine disruptors often do not show linear dose-response relationships typical of those found in traditional toxicological studies. For many compounds, low-dose exposure causes effects opposite to the ones seen after high-dose exposure. In addition, the timing of exposure has been found to be critical. Hence, to correctly assess the impact of endocrine disruptors on reproductive health requires in-depth knowledge of their mechanisms of action. This thesis aimed at identifying the mechanisms underlying the effects of cadmium (Cd), phthalates and phytoestrogens on testicular steroidogenesis. For this purpose, in vitro as well as in vivo models were used. Cd was found to inhibit testosterone synthesis in vivo by down-regulating LH receptor gene expression and reducing the testicular levels of cAMP and StAR protein. In addition, Cd caused a pronounced increase in testicular prostaglandin F2ɑ (PGF2ɑ), suggesting that Cd exerts its suppressive effect on steroidogenesis also by inducing the inhibitory PKC pathway. Pre-treatment with zinc (Zn) protected completely against Cd-induced effects on testosterone and PGF2ɑ. Furthermore, we observed that Cd exposure increased glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA expression in the testis. GAPDH is a potent coactivator of androgen receptor-mediated transcription and the up-regulation found in our study is probably a compensatory response to reduced testosterone concentrations. This finding is interesting since GAPDH has been proposed to have an important role in the regulation of apoptosis as well as sperm motility. We discovered that mono-(2-ethylhexyl) phthalate (MEHP), the active metabolite of the frequently used phthalate di-(2-ethylhexyl) phthalate (DEHP), stimulates Leydig cell steroidogenesis in vitro, by a cAMP- and StAR-independent mechanism. MEHP exposure caused a similar effect in granulosa cells. Gene expression analysis revealed that MEHP is likely to stimulate steroidogenesis by increasing the amount of cholesterol available for steroid synthesis. In the last investigation, we examined the effects of low-dose phytoestrogen exposure on testosterone synthesis during puberty in male goats. Isoflavones present in clover increased plasma concentrations of testosterone and free as well as total triiodothyronine (T3). T3 has previously been shown to induce testosterone synthesis and it is possible that an elevated T3 secretion underlies the increased plasma testosterone levels. Reduced fertility and reproductive tract malformations affect both the individual and the society. Hence, a sound knowledge of reproductive toxicants is of crucial importance. The findings presented in this thesis provide new insights into the reproductive toxicology of endocrine disruptors and may be valuable for risk assessment purposes.
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| 9. |
- Heinälä, Milla, et al.
(författare)
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Survey on methodologies in the risk assessment of chemical exposures in emergency response situations in Europe
- 2013
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Ingår i: Journal of Hazardous Materials. - : Elsevier. - 0304-3894 .- 1873-3336. ; 244, s. 545-554
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Tidskriftsartikel (refereegranskat)abstract
- A scientifically sound assessment of the risk to human health resulting from acute chemical releases is the cornerstone for chemical incident prevention, preparedness and response. Although the general methodology to identify acute toxicity of chemicals has not substantially changed in the last decades, there is ongoing debate on the current approaches for human health risk assessment in scenarios involving acute chemical releases.A survey was conducted to identify 1) the most important present and potential future chemical incident scenarios and anticipated changes in chemical incidents or their management; 2) information, tools and guidance used in different countries to assess health risks from acute chemical releases; and 3) needs for new information, tools, guidance and expertise to enable the valid and rapid health risk assessment of acute chemical exposures.According to the results, there is an obvious variability in risk assessment practices within Europe. The multiplicity of acute exposure reference values appears to result in variable practices. There is a need for training especially on the practical application of acute exposure reference values. Although acutely toxic and irritating/corrosive chemicals will remain serious risks also in future the development of plausible scenarios for potential emerging risks is also needed. This includes risks from new mixtures and chemicals (e.g. nanoparticles).
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| 10. |
- Leffler, David, et al.
(författare)
-
An adaptive route choice model for integrated fixed and flexible transit systems
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Over the past decade, there has been a surge of interest in the transport community in the application of agent-based simulation models to evaluate flexible transit solutions characterized by different degrees of short-term flexibility in routing and scheduling. A central modeling decision in the development of an agent-based simulation model for the evaluation of flexible transit is how one chooses to represent the mode- and route-choices of travelers. The real-time adaptive behavior of travelers is intuitively important to model in the presence of a flexible transit service, where the routing and scheduling of vehicles is highly dependent on supply-demand dynamics at a closer to real-time temporal resolution. We propose a utility-based transit route-choice model with representation of within-day adaptive travel behavior and between-day learning where station-based fixed-transit, flexible-transit, and active-mode alternatives may be dynamically combined in a single path. To enable experimentation, this route-choice model is implemented within an agent-based dynamic public transit simulation framework. Model properties are first explored in a choice between fixed- and flexible-transit modes for a toy network. The framework is then applied to illustrate level-of-service trade-offs and analyze traveler mode choices within a mixed fixed- and flexible transit system in a case study based on a real-life branched transit service in Stockholm, Sweden.
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| 11. |
- Leffler, David, et al.
(författare)
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An adaptive route choice model for integrated fixed and flexible transit systems
- 2024
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Ingår i: Transportmetrica B. - : Informa UK Limited. - 2168-0566. ; 12:1
-
Tidskriftsartikel (refereegranskat)abstract
- Over the past decade, there has been a surge of interest in the application of agent-based simulation models to evaluate flexible transit solutions characterized by different degrees of short-term flexibility in routing and scheduling. A central modelling decision in the development is how one chooses to represent the mode- and route-choices of travellers. The real-time adaptive behaviour of travellers is important to model in the presence of a flexible transit service, where the routing and scheduling of vehicles is highly dependent on supply-demand dynamics at a near real-time temporal resolution. We propose a utility-based transit route-choice model with representation of within-day adaptive travel behaviour and between-day learning where station-based fixed-transit, flexible-transit, and active-mode alternatives may be dynamically combined in a single path. To enable experimentation, this route-choice model is implemented within an agent-based dynamic public transit simulation framework. We first explore model properties in a choice between fixed- and flexible-transit modes for a toy network. The adaptive route choice framework is then applied to a case study based on a real-life branched transit service in Stockholm, Sweden. This case study illustrates level-of-service trade-offs, in terms of waiting times and in-vehicle times, between passenger groups and analyzes traveller mode choices within a mixed fixed- and flexible transit system. Results show that the proposed framework is capable of capturing dynamic route choices in mixed flexible and fixed transit systems and that the day-to-day learning model leads to stable fixed-flexible mode choices.
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| 12. |
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| 13. |
- Leffler, David, et al.
(författare)
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Distribution of passenger costs in fixed versus flexible station-based feeder services
- 2020
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Ingår i: Transportation Research Procedia. - : Elsevier B.V.. - 2352-1465. ; , s. 179-186
-
Konferensbidrag (refereegranskat)abstract
- This paper presents a comparative analysis of demand-responsive and fixed-schedule, fixed route operations for a simplified station-based feeder to mass transit scenario. Traffic dynamics, demand-responsive fleet coordination, and the behaviour of individual transit users are represented using a public transit simulation framework. Each operational strategy is simulated for varying levels of demand and two fleet compositions with respect to vehicle capacities and fleet size are compared. The services are evaluated based on resulting passenger waiting times, in-vehicles times and additional waiting time if one is denied boarding a fully occupied vehicle. Results indicate that dividing planned service capacity into larger fleets of smaller vehicles can provide a higher level-of-service to passengers. On an aggregate level, utilizing a fixed operational policy results in shorter and more reliable waiting times for levels of demand where there is slack in service capacity. In scenarios where planned service capacity is sometimes exceeded, the on-demand service provides a more even spatial distribution of passenger waiting times, relative to a fixed service.
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| 14. |
- Leffler, David, et al.
(författare)
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Real-time short-turning in high frequency bus services based on passenger cost
- 2017
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Ingår i: 5th IEEE International Conference on Models and Technologies for Intelligent Transportation Systems, MT-ITS 2017 - Proceedings. - : Institute of Electrical and Electronics Engineers (IEEE). - 9781509064847 ; , s. 861-866
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Konferensbidrag (refereegranskat)abstract
- In this paper, we deal with the problem of determining when and where a bus should short-turn on a single bi-directional line in real-time. We formulate a decision rule for when to short-turn among candidate short-turning locations that is based on the objective of minimizing total generalized passenger travel cost including waiting times and forced transfer. Computational results and analysis are provided via a simulation study in BusMezzo, a dynamic, agent-based transit operations and assignment model that represents both vehicle as well as passenger progression. The simulation framework allows us to evaluate the resulting trade-off between passenger costs and transit performance that occur when a decision to short-turn is made. The proposed short-turning strategy is applied to a real-world high-frequency transit line in Stockholm, Sweden.
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| 15. |
- Leffler, David
(författare)
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Simulation-based Evaluation of Fixed to Flexible Transit
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Emerging technologies have inspired a wide array of flexible public transit system designs characterized by varying degrees of demand-responsive routing and scheduling. The availability and synthesis of new data sources with higher degrees of spatial and temporal richness brought on by advancements in Intelligent Transport Systems allow for monitoring and responding to evolving supply-demand imbalances in real-time. The emergence of smartphone-enabled ride-pooling services and the development of automated vehicles have shown promise in offering flexible transit systems at a higher level-of-service and a lower per-vehicle operational cost.Preliminary studies have indicated that reallocating resources from fixed transit services with low utilization rates to flexible transit services can improve public transit accessibility in low demand-density areas. Studies have also shown that shared automated vehicle services can drastically reduce the number of vehicles required to serve urban transport demand, reducing congestion and pollution. New technologies and flexible transit designs could foster city infrastructure planning oriented around people instead of cars. However, if high enough levels of ride-pooling and integration with existing high-capacity transit are not achieved, there are also indications that such services can poach passengers from more sustainable modes of transportation, increase total vehicle-kilometers traveled, and amplify trends of urban congestion.A question that arises is how to evaluate the effects of novel flexible transport solutions as a competing or complementary alternative to traditional fixed public transit under alternative demand settings, technological settings, road network topologies, and objectives. Flexible transit systems are difficult to trial in parallel with the technologies that inspire their design, due to their cost of implementation and the time frame required for stable use patterns to emerge. Agent-based simulation frameworks have been utilized to systematically understand and develop theories around the dynamics of transport systems and traveler behavior using diverse data sources, while ideally also forecasting the effect of alternative transit designs and operational policies. Interest in applying agent-based simulation models to evaluate flexible transit systems has grown significantly over the past decade, however, are still limited in their ability to represent the vast flexible transit service design space. In this thesis, flexible public transit systems ranging from services with partially fixed routes and timetables to services with demand-responsive routes and timetables determined in real-time are appraised through extensions to the public transit simulation framework BusMezzo.In each of the included papers, a flexible transit service design inspired by Intelligent Transport Systems and automated vehicle use cases is developed. This system is formalized with simplifying assumptions to make the problem tractable in terms of modeling, and then implemented in BusMezzo. The system, model, and implementation are evaluated in several case studies based on recurring fixed public transit supply-demand scenarios. Through the work of this thesis, key level-of-service trade-offs between fixed and flexible transit operations are explored. The resulting simulation framework includes essential components for modeling supply-demand dynamics of mixed fixed and flexible transit systems and enables systematic evaluation of a wider range of emerging public transit designs and scenarios.
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| 16. |
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| 17. |
- Leffler, David
(författare)
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Simulation based evaluation of flexible transit
- 2019
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Transport authorities are faced with the challenge of making effective use of existing transportation infrastructure under increasing needs of transport accessibility, sustainability, and safety. The ongoing growth and adoption of shared mobility options, the anticipation of automated vehicles, and the increased availability of real-time data brought on with the developments of Intelligent Transport Systems, have all inspired many innovations in public transit design. The integration of these technologies in existing public transit holds great potential for operational planning and control, but is also notoriously difficult to evaluate. In the included papers, flexible operational policies that make use of real-time data and connected vehicles are developed and assessed through the extension of an existing public transit simulation framework, BusMezzo.Paper I explores the incorporation of flexibility in fixed urban transit via real-time short-turning, a fleet management strategy not often studied in a real-time context. In this paper, a decision rule for when and where a short-turn should occur based on predicted passenger costs is developed and evaluated in a case study of a bidirectional urban bus line in Stockholm, Sweden.Paper II focuses on the design and analysis of an automated feeder service. In this paper an extension of BusMezzo with a module for simulating a variety of flexible transit operations is presented. Estimated reductions in on-board crew costs with vehicle automation motivate a case study of two vehicle fleets where a fully demand-responsive operational policy is compared against fixed route and schedule operations.
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| 18. |
- Leffler, David, et al.
(författare)
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Simulation of fixed versus on-demand station-based feeder operations
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Motivated by lower predicted operational costs, and opportunities for efficient real-time control, automated, centrally coordinated vehicles have in many studies shown great potential as a shared resource within public transit. One particular use case that has grown in popularity over recent years is the application of smaller, automated shuttles as an on-demand feeder to mass transit solution. To investigate differences in fixed versus on-demand operational policies, this paper discusses the operational design and analysis of an automated feeder solution. To this end, a simulation model of demand-responsive transit is developed and incorporated into the transit simulation model BusMezzo. An estimation of operational cost reductions with vehicle automation motivates the case study of two fleets that are deemed comparable with respect to service capacity and operational cost per hour. Results from simulation studies of varying levels of demand indicate that the on-demand policy reduces average total passenger travel times and, for the larger fleet, lowers average vehicle-kilometers traveled per passenger relative fixed service operations. Without achieving a competitive reduction in waiting times, however, on-demand coordination often underperforms with respect to level-of-service and reliability when compared with fixed service operations. When there is slack in fixed service capacity, the performance of the on-demand service outperforms the fixed service with respect to both level-of-service and vehicle utilization only for the lowest demand level tested and the smaller fleet. Average total system costs under on-demand operations improve, however, for the lowest demand levels and the larger fleet due to a reduction in vehicle-kilometers traveled relative a fixed service. When fixed service capacity is exceeded it is found that on-demand coordination outperforms fixed operations with respect to average level-of-service, vehicle-kilometers traveled, and total system costs. Furthermore, when planned service capacity is exceeded, it is found that total passenger waiting time is more equally distributed under on-demand operations relative to fixed.
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| 19. |
- Leffler, David, et al.
(författare)
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Simulation of fixed versus on-demand station-based feeder operations
- 2021
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Ingår i: Transportation Research Part C. - : Elsevier BV. - 0968-090X .- 1879-2359. ; 132
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Tidskriftsartikel (refereegranskat)abstract
- The paper develops a simulation model and evaluates fixed versus on-demand operational designs of a station-based automated feeder service. The evaluation considers the operational cost and average passenger level-of-service trade-offs as well as distributional differences in waiting times. Two case studies are used to evaluate such trade-offs under different fleet compositions; (1) a simple circular network feeder service; (2) a case based on a real-world coordinated branched service in Stockholm, combining fixed-line services on the trunk portion with a flexible feeder service on the branches. Results for the circular network indicate that there are benefits in utilizing an on-demand operational policy for the lowest and highest demand levels tested. When fixed service capacity is exceeded, it is found that there are potential benefits in on-demand operations with respect to average level-of-service, as well as delivering a more even distribution of passenger waiting times. Results for the real-world case show that combining DRT on branches with fixed services on the trunk improves the overall median waiting times for all DRT scenarios and provides substantial improvements for passengers on the trunk, at the cost of more variable, and less equitable waiting times on the branches. For larger fleet sizes, generalized travel costs are reduced with and without rebalancing and level-of service provided to branch-to-branch passengers is improved considerably by rebalancing idling vehicles to branch end-stops. The case studies demonstrate the usefulness of the simulation framework in evaluating trade-offs between fixed and on-demand service design variables and their effects on disaggregate level-of-service provided for stop-based feeder services.
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| 20. |
- Leffler, David, et al.
(författare)
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Utvärdering av delade självkörande fordon inom efterfrågestyrd kollektivtrafik genom simulering
- 2019
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Bakgrund: Det finns påståenden om att genom användning av delade självkörande fordon inom flexibel-, eller efterfrågestyrd kollektivtrafik (EKT) skulle man kunna förbättra mobiliteten för personer med begränsad tillgång till en privat bil och för personer utan adekvat tillgång till högkapacitets kollektivtrafik. Oavsett om det är automatiserat eller inte, så är dock kostnadseffektiviteten och servicenivån som förses en passagerare av en EKT-flotta starkt beroende av förmågan att effektivt kunna matcha fordon till passagerarbegäran i realtid. Vidare kan flexibla rutter och tidtabeller öka osäkerheten om förväntade väntetider och restider för passagerare i förhållande till en traditionell tjänst med fast tidtabell och rutt. Den uppfattade tillförlitligheten hos tjänsten kan i sin tur kraftigt påverka en resenärs val av rutt och transportmedel när det finns tillgång till andra alternativ, vilket i sin tur bidrar till osäkerheten i uppskattningar av framtida efterfrågan när den matchas till EK-flottan i realtid.Metoder: Även om självkörande fordon utvecklas i hög takt, har de fortfarande inte uppnått nivåer av automatisering och säkerhet som möjliggör att de används i bredare tillämpningar. EKT-system är också svåra att pröva, på grund av höga implementeringskostnader samt osäkerheten i efterfrågan som resulterar från varierande design och strategier för hur EKT-flottan samordnas. Simulering är således ett viktigt verktyg för att utvärdera självkörande fordon inom EKT. För att simulera EKT utvecklades en justerbar modell för att dynamiskt matcha delade fordon till stokastiskt genererade passageraranrop. Denna modell integrerades sedan med en simuleringsmodell för kollektivtrafik som representerar både trafikdynamik samt inlärning och adaptering av individuella passagerare.Resultat: Med detta ramverk kan vi bättre studera interaktionen mellan operativa egenskaper av en EKT-tjänst och dess resulterande effekter på en resenärs val av rutt, transportmedel och generaliserade kostnader. I denna presentation presenteras ramverket för att studera EKT samt en demonstration av dess tillämpning för att utvärdera en automatiserad EKT-tjänst som ett samexisterande alternativ till en traditionell kollektivtrafiktjänst med förutbestämd tidtabell och rutt.
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| 21. |
- Lin, Chi-lou, et al.
(författare)
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Galectin-3 Targeted Therapy with a Small Molecule Inhibitor Activates Apoptosis and Enhances Both Chemosensitivity and Radiosensitivity in Papillary Thyroid Cancer
- 2009
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Ingår i: Molecular Cancer Research. - 1557-3125. ; 7:10, s. 1655-1662
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Tidskriftsartikel (refereegranskat)abstract
- Although most patients with papillary thyroid cancer (PTC) have favorable outcomes, some have advanced PTC that is refractory to external beam radiation and systemic chemotherapy. Galectin-3 (Gal-3) is a beta-galactoside-binding protein with antiapoptotic activity that is consistently overexpressed in PTC. The purpose of this study is to determine if Gal-3 inhibition promotes apoptosis, chemosensitivity, and radiosensitivity in PTC. PTC cell lines (8505-C and TPC-1) and human ex vivo PTC were treated with a highly specific small molecule inhibitor of Gal-3 (Td131_1). Apoptotic activity was determined by flow cytometric analysis as well as caspase-3 and PARP cleavage. The minimum inhibitory concentrations of Td131_1 and doxorubicin were determined, and their combined effects were measured to test for synergistic activity. The effects of Td131_1 on radiosensitivity were determined by a clonogenic assay. Td131_1 promoted apoptosis, improved radiosensitivity, and synergistically enhanced chemosensitivity to doxorubicin in PTC cell lines. In PTC ex vivo, Td131_1 treatment alone induced the cleavage of caspase-3 and PARP. Td131_1 and doxorubicin together activated apoptosis in PTC ex vivo to a greater degree than their combined individual effects. Td131_1 activated apoptosis and had synergistic activity with doxorubicin in PTC. We conclude that Gal-3 targeted therapy is a promising therapeutic strategy for advanced PTC that is refractory to surgery and radioactive iodine therapy. (Mol Cancer Res 2009;7(10):1655-62)
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| 22. |
- Ludvigsson, Jonas F., 1969-, et al.
(författare)
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Outcome measures in coeliac disease trials : the Tampere recommendations
- 2018
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Ingår i: Gut. - : BMJ Publishing Group Ltd. - 0017-5749 .- 1468-3288. ; 67:8, s. 1410-1424
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Tidskriftsartikel (refereegranskat)abstract
- Objective: A gluten-free diet is the only treatment option of coeliac disease, but recently an increasing number of trials have begun to explore alternative treatment strategies. We aimed to review the literature on coeliac disease therapeutic trials and issue recommendations for outcome measures.Design: Based on a literature review of 10 062 references, we (17 researchers and 2 patient representatives from 10 countries) reviewed the use and suitability of both clinical and non-clinical outcome measures. We then made expert-based recommendations for use of these outcomes in coeliac disease trials and identified areas where research is needed. Results: We comment on the use of histology, serology, clinical outcome assessment (including patient-reported outcomes), quality of life and immunological tools including gluten immunogenic peptides for trials in coeliac disease.Conclusion: Careful evaluation and reporting of outcome measures will increase transparency and comparability of coeliac disease therapeutic trials, and will benefit patients, healthcare and the pharmaceutical industry.
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| 23. |
- Ludvigsson, Jonas F., et al.
(författare)
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The Oslo definitions for coeliac disease and related terms
- 2013
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Ingår i: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 62:1, s. 43-52
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Tidskriftsartikel (refereegranskat)abstract
- Objective The literature suggests a lack of consensus on the use of terms related to coeliac disease (CD) and gluten. Design A multidisciplinary task force of 16 physicians from seven countries used the electronic database PubMed to review the literature for CD-related terms up to January 2011. Teams of physicians then suggested a definition for each term, followed by feedback of these definitions through a web survey on definitions, discussions during a meeting in Oslo and phone conferences. In addition to 'CD', the following descriptors of CD were evaluated (in alphabetical order): asymptomatic, atypical, classical, latent, non-classical, overt, paediatric classical, potential, refractory, silent, subclinical, symptomatic, typical, CD serology, CD autoimmunity, genetically at risk of CD, dermatitis herpetiformis, gluten, gluten ataxia, gluten intolerance, gluten sensitivity and gliadin-specific antibodies. Results CD was defined as 'a chronic small intestinal immune-mediated enteropathy precipitated by exposure to dietary gluten in genetically predisposed individuals'. Classical CD was defined as 'CD presenting with signs and symptoms of malabsorption. Diarrhoea, steatorrhoea, weight loss or growth failure is required.' 'Gluten-related disorders' is the suggested umbrella term for all diseases triggered by gluten and the term gluten intolerance should not to be used. Other definitions are presented in the paper. Conclusion This paper presents the Oslo definitions for CD-related terms.
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| 24. |
- Marques, Sueli, et al.
(författare)
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Transcriptional Convergence of Oligodendrocyte Lineage Progenitors during Development
- 2018
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Ingår i: Developmental Cell. - : Elsevier BV. - 1878-1551 .- 1534-5807. ; 46:4, s. 504-517
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Tidskriftsartikel (refereegranskat)abstract
- Pdgfra+ oligodendrocyte precursor cells (OPCs) arise in distinct specification waves during embryogenesis in the central nervous system (CNS). It is unclear whether there is a correlation between these waves and different oligodendrocyte (OL) states at adult stages. Here, we present bulk and single-cell transcriptomics resources providing insights on how transitions between these states occur. We found that post-natal OPCs from brain and spinal cord present similar transcriptional signatures. Moreover, post-natal OPC progeny of E13.5 Pdgfra+ cells present electrophysiological and transcriptional profiles similar to OPCs derived from subsequent specification waves, indicating that Pdgfra+ pre-OPCs rewire their transcriptional network during development. Single-cell RNA-seq and lineage tracing indicates that a subset of E13.5 Pdgfra+ cells originates cells of the pericyte lineage. Thus, our results indicate that embryonic Pdgfra+ cells in the CNS give rise to distinct post-natal cell lineages, including OPCs with convergent transcriptional profiles in different CNS regions.
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| 25. |
- Proletov, Ian, et al.
(författare)
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Primary and secondary glomerulonephritides 1.
- 2014
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Ingår i: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. - : Oxford University Press (OUP). - 1460-2385. ; 29 Suppl 3:May, s. 186-200
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Tidskriftsartikel (refereegranskat)
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| 26. |
- Stowell, Sean R, et al.
(författare)
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Galectins-1, -2 and -3 exhibit differential recognition of sialylated glycans and blood group antigens
- 2008
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Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 283:15, s. 10109-10123
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Tidskriftsartikel (refereegranskat)abstract
- Human galectins have functionally divergent roles, although most of the members of the galectin family bind weakly to the simple disaccharide lactose (Galss1-4Glc). To assess galectin-glycan interactions in more detail, we explored the binding of several important galectins (Gal-1, Gal-2, and Gal-3) on a glycan microarray containing hundreds of structurally diverse glycans. All three galectins exhibited unique glycan binding characteristics. Only Gal-1 and Gal-2 bound complex-type N-glycans and extended core 1 O-glycans with high affinity, while Gal-2 and Gal-3, but not Gal-1, bound A and B blood group antigens. Gal-2 failed to recognize any sialylated glycans regardless of linkage, whereas Gal-1 and Gal-3 bound a2-3, but not a2-6 sialylated glycans. All galectins showed higher binding to sulfated glycans relative to unsulfated ones. Each galectin exhibited higher binding for glycans with poly-N-acetyllactosamine (PL) sequences (Galss1-4GlcNAc)n when compared to N-acetyllactosamine (Galss1-4GlcNAc) in the microarray. However, only Gal-3 preferred PL when assessed by solution-based surface plasmon resonance. Removal of the terminal galactose residue in PL abrogated its recognition by Gal-1 and Gal-2 while having no substantial effect on Gal-3 recognition, demonstrating that Gal-3 recognizes internal N-acetyllactosamine units. These results provide novel insights into the functional constraints of glycan recognition by each galectin and underscore the basis for differences in biological activity.
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| 27. |
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| 28. |
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| 29. |
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| 30. |
- Zhu, Shun-Wei, et al.
(författare)
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Influence of environmental manipulation on exploratory behaviour in male BDNF knockout mice
- 2009
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Ingår i: Behavioural Brain Research. - : Elsevier BV. - 0166-4328 .- 1872-7549. ; 197:2, s. 339-346
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Tidskriftsartikel (refereegranskat)abstract
- It is widely accepted that brain derived neurotrophic factor (BDNF) plays a crucial role in mediating changes in learning and memory performance induced by environmental conditions. In order to ascertain whether BDNF modulates environmentally induced changes in exploratory behaviour, we examined mice carrying a deletion in one copy of the BDNF gene. Young heterozygous male BDNF knockout mice (BDNF+/−) and their wild-type (WT) controls were exposed to the enriched environment condition (EC) or the standard condition (SC) for 8 weeks. Exploratory behaviour was assessed in the open-field (OF) and hole-board (HB) test. Brains from EC and SC reared animals were processed for Golgi-Cox staining and the dendritic spine density in the dentate gyrus (DG) and CA1 hippocampal regions were examined. We found behavioural differences both due to the genetic modification and the environmental manipulation, with the BDNF+/− mice being more active in the OF whereas the EC mice had increased exploratory behaviour in the HB test. Environmental enrichment also led to an increase in dendritic spines in the hippocampal CA1 region and DG of the wild-type mice. This effect was also found in the enriched BDNF+/− mice, but was less pronounced. Our findings support the critical role of BDNF in behavioural and neural plasticity associated with environmental enrichment and suggest that besides maze learning performance, BDNF dependent mechanisms are also involved in other aspects of behaviour. Here we provide additional evidence that exploratory activity is influenced by BDNF.
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