| 1. |
|
|
| 2. |
- Angot, Elodie, et al.
(författare)
-
Alpha-Synuclein Cell-to-Cell Transfer and Seeding in Grafted Dopaminergic Neurons In Vivo.
- 2012
-
Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:6
-
Tidskriftsartikel (refereegranskat)abstract
- Several people with Parkinson's disease have been treated with intrastriatal grafts of fetal dopaminergic neurons. Following autopsy, 10-22 years after surgery, some of the grafted neurons contained Lewy bodies similar to those observed in the host brain. Numerous studies have attempted to explain these findings in cell and animal models. In cell culture, α-synuclein has been found to transfer from one cell to another, via mechanisms that include exosomal transport and endocytosis, and in certain cases seed aggregation in the recipient cell. In animal models, transfer of α-synuclein from host brain cells to grafted neurons has been shown, but the reported frequency of the event has been relatively low and little is known about the underlying mechanisms as well as the fate of the transferred α-synuclein. We now demonstrate frequent transfer of α-synuclein from a rat brain engineered to overexpress human α-synuclein to grafted dopaminergic neurons. Further, we show that this model can be used to explore mechanisms underlying cell-to-cell transfer of α-synuclein. Thus, we present evidence both for the involvement of endocytosis in α-synuclein uptake in vivo, and for seeding of aggregation of endogenous α-synuclein in the recipient neuron by the transferred α-synuclein. Finally, we show that, at least in a subset of the studied cells, the transmitted α-synuclein is sensitive to proteinase K. Our new model system could be used to test compounds that inhibit cell-to-cell transfer of α-synuclein and therefore might retard progression of Parkinson neuropathology.
|
|
| 3. |
- Barker, Roger A, et al.
(författare)
-
Are Stem Cell-Based Therapies for Parkinson's Disease Ready for the Clinic in 2016?
- 2016
-
Ingår i: Journal of Parkinson's Disease. - 1877-718X. ; 6:1, s. 57-63
-
Tidskriftsartikel (refereegranskat)abstract
- Recent news of an impending clinical cell transplantation trial in Parkinson's disease using parthenogenetic stem cells as a source of donor tissue have raised hopes in the patient community and sparked discussion in the research community. Based on discussions held by a global collaborative initiative on translation of stem cell therapy in Parkinson's disease, we have identified a set of key questions that we believe should be addressed ahead of every clinical stem cell-based transplantation trial in this disorder. In this article, we first provide a short history of cell therapy in Parkinson's disease and briefly describe the current state-of-art regarding human stem cell-derived dopamine neurons for use in any patient trial. With this background information as a foundation, we then discuss each of the key questions in relation to the upcoming therapeutic trial and critically assess if the time is ripe for clinical translation of parthenogenetic stem cell technology in Parkinson's disease.
|
|
| 4. |
- Barker, Roger A., et al.
(författare)
-
GDNF and Parkinson's Disease : Where Next? A Summary from a Recent Workshop
- 2020
-
Ingår i: Journal of Parkinson's Disease. - 1877-7171. ; 10:3, s. 875-891
-
Tidskriftsartikel (refereegranskat)abstract
- The concept of repairing the brain with growth factors has been pursued for many years in a variety of neurodegenerative diseases including primarily Parkinson's disease (PD) using glial cell line-derived neurotrophic factor (GDNF). This neurotrophic factor was discovered in 1993 and shown to have selective effects on promoting survival and regeneration of certain populations of neurons including the dopaminergic nigrostriatal pathway. These observations led to a series of clinical trials in PD patients including using infusions or gene delivery of GDNF or the related growth factor, neurturin (NRTN). Initial studies, some of which were open label, suggested that this approach could be of value in PD when the agent was injected into the putamen rather than the cerebral ventricles. In subsequent double-blind, placebo-controlled trials, the most recent reporting in 2019, treatment with GDNF did not achieve its primary end point. As a result, there has been uncertainty as to whether GDNF (and by extrapolation, related GDNF family neurotrophic factors) has merit in the future treatment of PD. To critically appraise the existing work and its future, a special workshop was held to discuss and debate this issue. This paper is a summary of that meeting with recommendations on whether there is a future for this therapeutic approach and also what any future PD trial involving GDNF and other GDNF family neurotrophic factors should consider in its design.
|
|
| 5. |
|
|
| 6. |
- Björklund, Anders, et al.
(författare)
-
Repairing the Parkinson Brain
- 2021
-
Ingår i: Journal of Parkinson's Disease. - 1877-718X. ; 11:s2, s. 123-125
-
Tidskriftsartikel (refereegranskat)
|
|
| 7. |
- Björklund, Emil, et al.
(författare)
-
Analysis of protein-ligand interactions from titrations and nuclear magnetic resonance relaxation dispersions
- 2022
-
Ingår i: Protein Science. - : Wiley. - 0961-8368 .- 1469-896X. ; 31:1, s. 301-307
-
Tidskriftsartikel (refereegranskat)abstract
- We present PLIS, a publicly available, open-source software for the determination of protein-ligand dissociation constants that can be used to characterize biological processes or to shed light on biophysical aspects of interactions. PLIS can analyze data from titration experiments monitored by for instance fluorescence spectroscopy or from nuclear magnetic resonance relaxation dispersion experiments. In addition to analysis of experimental data, PLIS includes functionality for generation of synthetic data, useful for understanding how different parameters effect the data in order to better analyze experiments.
|
|
| 8. |
- Björklund, Patrik, 1970-, et al.
(författare)
-
A Column Generation Method for Spatial TDMA Scheduling in Ad Hoc Networks
- 2004
-
Ingår i: Ad hoc networks. - : Elsevier BV. - 1570-8705 .- 1570-8713. ; 2:Issue 4, s. 405-418
-
Tidskriftsartikel (refereegranskat)abstract
- An ad hoc network can be set up by a number of units without the need of any permanent infrastructure. Two units establish a communication link if the channel quality is sufficiently high. As not all pairs of units can establish direct links, traffic between two units may have to be relayed through other units. This is known as the multi-hop functionality. In military command and control systems, ad hoc networks are also referred to as multi-hop radio networks. Spatial TDMA (STDMA) is a scheme for access control in ad hoc networks. STDMA improves TDMA by allowing simultaneous transmission of multiple units. In this paper, we study the optimization problem of STDMA scheduling, where the objective is to find minimum-length schedules. Previous work for this problem has focused on heuristics, whose performance is difficult to analyze when optimal solutions are not known. We develop novel mathematical programming formulations for this problem, and present a column generation solution method. Our numerical experiments show that the method generates a very tight bound to the optimal schedule length, and thereby enables optimal or near-optimal solutions. The column generation method can be used to provide benchmarks when evaluating STDMA scheduling algorithms. In particular, we use the bound obtained in the column generation method to evaluate a simple greedy algorithm that is suitable for distributed implementations.
|
|
| 9. |
|
|
| 10. |
|
|
| 11. |
- Björklund, Patrik, 1970-, et al.
(författare)
-
A Simulated Annealing Algorithm for Frequency Assignment in Frequency Hopping GSM Networks
- 2003
-
Ingår i: International Conference on Computer, Communication and Control Technolgies CCCT 03,2003. - Orlando : IIIS. ; , s. 155-
-
Konferensbidrag (refereegranskat)abstract
- We consider the frequency assignment problem in frequency hopping GSM networks, where the task is to construct and assign lists of frequencies to blocks of transceivers, such that the total interference is minimized. We present a mathematical model and describe a simulated annealing algorithm. The algorithm explores the solution space by solving an integer program in each iteration. Computational experiments for real-life and synthesized networks show that considerable interference reduction can be achieved using the algorithm.
|
|
| 12. |
- Björklund, Patrik, 1970-
(författare)
-
Applications of Resource Optimization in Wireless Networks
- 2006
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The demand for wireless communications is increasing every year, but the available resources are not increasing at the same rate. It is very important that the radio resources are used in an efficient way allowing the networks to support as many users as possible. The three types of networks studied in this thesis are frequency hopping GSM networks, ad hoc multi-hop networks and WCDMA networks.One type of network with a promising future is ad hoc multi-hop networks. The users in this kind of networks communicate with each other without base stations. Instead the signal can be sent directly between two users, or relayed over one or several other users before the final destination is reached. Resources are shared by letting the users transmit in time slots. The problem studied is to minimize the number of time slots used, when the users broadcast. Two different optimization models are developed for assigning time slots to the users. A reduction of the number of time slots means a shorter delay for a user to transmit next time.The rapid growth of the number of subscribers in cellular networks requires efficient cell planning methods. The trend of smaller cell sizes in urban areas for higher capacity raise the need for more efficient spectrum usage. Since the infrastructure of a second generation cellular system, such as GSM, already exists, and the available bandwidth of an operator is limited, frequency planning methods are of utmost importance. Because of the limited bandwidth in a GSM network, the frequencies must be reused. When planning a GSM network the frequencies can not be reused too tightly due to interference. The frequency planning problem in a GSM network is a very complex task. In this thesis an optimization model for frequency assignment in a frequency hopping GSM network is developed. The problem is to assign frequencies to the cells in the network, while keeping the interference to a minimum. Different meta heuristic methods such as tabu search and simulated annealing are used to solve the problem. The results show that the interference levels can be reduced to allow a capacity increase.The demand for sending more information over the wireless communication systems requires more bandwidth. Voice communication was handled well by the second generation cellular systems. The third generation of mobile telecommunication systems will handle data transmissions in a greater extent. The last type of network considered in the thesis is a WCDMA cellular network. The aim is to schedule the transmission of packet data from the base station to the users. Scheduling models that maximize the utility are developed for both the downlink shared channel and the high speed downlink shared channel.
|
|
| 13. |
- Björklund, Patrik, et al.
(författare)
-
Optimized planning of frequency hopping in cellular networks
- 2005
-
Ingår i: Computers & Operations Research. - 0305-0548 .- 1873-765X. ; 32:1, s. 169-186
-
Tidskriftsartikel (refereegranskat)abstract
- We consider a generalization of the classical frequency assignment problem. The generalization arises when frequency hopping is used in a cellular network. The planning problem concerns assigning lists of frequencies to blocks of transceivers, such that the total interference is minimized. This problem is considerably more difficult than the classical frequency assignment problem, because of the large number of possible frequency lists. We provide the technical background that motivates our study, and present a mathematical model which includes the classical frequency assignment problem as a special case. We describe a simulated annealing algorithm. The algorithm explores the solution space by solving an integer program in each iteration. We report computational results for real-life and synthesized networks. © 2003 Elsevier Ltd. All rights reserved.
|
|
| 14. |
- Björklund, Patrik, 1970-, et al.
(författare)
-
Resource Optimization of Spatial TDMA in Ad Hoc Radio networks : A Column Generation Approach
- 2003
-
Ingår i: IEEE INFOCOM 2003,2003. - San Francisco : IEEE. ; , s. 818-
-
Konferensbidrag (refereegranskat)abstract
- Wireless communications using ad hoc networks are receiving an increasing interest. The most attractive feature of ad hoc networks is the flexibility. The network is set up by a number of units in an ad hoc manner, without the need of any fixed infrastructure. Communication links are established between two units if the signal strength is sufficiently high. As not all pairs of nodes can establish direct links, the traffic between two units may have to be relayed through other units. This is known as the multihop functionality. Design of ad hoc networks is a challenging task. In this paper we study the problem of resource allocation with spatial TDMA (STDMA) as the access control scheme. Previous work for this problem has mainly focused on heuristics, whose performance is difficult to analyze when optimal solutions are not known. We develop, for both node-oriented and link-oriented allocation strategies, mathematical programming formulations for resource optimization. We further present a column generation approach, which, in our numerical experiments, constantly yields optimal or near-optimal solutions. Our results provide important benchmarks when evaluating heuristic on-line algorithms for resource optimization using STDMA.
|
|
| 15. |
- Björklund, Patrik, 1970-
(författare)
-
Two Resource Optimization Applications in Wireless Networks
- 2002
-
Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The demand for wireless applications is increasing every year. In a couple of years, much of the traffic in the networks is packet switched data. The radio resources are not increasing at the same rate as the demand for wireless communication. It is very important that the radio resources are used in an efficient manner allowing the networks to support as many users as possible. Resource allocation in wireless networks is about using the radio resources in an efficient way. The two types of networks studied in this thesis are frequency hopping GSM networks and ad hoc multi-hop networks.The rapid growth of the number of subscribers in cellular networks requires efficient cell planning methods. The trend of smaller cell sizes in urban areas for higher capacity raise the need for more efficient spectrum usage. Since the infrastructure of a second generation cellular system, such as GSM, already exists, and the available bandwidth of an operator is limited, frequency planning methods are of utmost importance. Because of the limited bandwidth in a GSM network, the frequencies must be reused. When planning a GSM network the frequencies can not be reused too tightly due to interferences between co-channel and adjacent-channel frequencies. The frequency planning problem in a GSM network is a very complex task. In this thesis an optimization model for frequency assignment in a frequency hopping GSM network is developed. The problem is to assign frequencies to the cells in the network, while keeping the interference to a minimum. Different meta heuristic methods such as tabu search and simulated annealing are used to solve the problem.Another type of network with a promising future are ad hoc multi-hop networks. The users in this kind of networks communicate with each other without base stations. Instead the signal can be sent directly between two users, or relayed over one or several other users before the final destination is reached. Resources are shared by letting the users transmit in time slots. The problem studied is to minimize the number of time slots used, when the users broadcast. Two different optimization models are developed for assigning time slots to the users. The models are solved by different techniques.In the two different types of networks investigated, frequency hopping GSM networks and ad hoc multi-hop networks, resource allocation achieves better performance. In the former network, the interference levels can be reduced to allow a capacity increase. In the latter the number of time slots can be reduced to decrease the delay for a user.
|
|
| 16. |
- Björklund, Patrik, et al.
(författare)
-
Västerås slott : Slott och borgar
- 2000
-
Rapport (populärvet., debatt m.m.)abstract
- En majoritet av dagens byggnadsuppgifter gäller att hantera det redan byggda. När vi står inför situationen att restaurera en befintlig byggnad är det viktigt att förstå olika tidsperioders stilideal liksom byggnadsteknik och material. Först då kan vi göra en väl avvägd analys, som tar tillvara och utvecklar de kvaliteter som byggnaderna själva besitter. Därför är utbildningen upplagd som ett växelspel mellan föreläsningar, seminarier, exkursioner och en för året vald studieuppgift.Slott och borgar har varit läsårets tema. Vi har valt att arbeta med Västerås och Örebro slott - två ganska bortglömda Vasaslott som är väl värda att lyfta fram. Särskilt har vi studerat de senaste 300 årens förändringar, som inte tidigare ägnats lika stora forskarmöda som medelitden och Vasatiden. I dessa två exempel finns en provkarta på estetiska, praktiska och tekniska ingrepp från Carl Hårlemans tid och fram till idag.Studierna har således omfattat både gestaltning, funktion och byggnadsteknik. Avsikten är att visa på kvaliteter i de omvandlingar och restaureringar som skett, men också att peka på problem och analysera olika möjligheter inför framtiden. Arbetet har skett i samarbete med Statens fastighetsverk och är tänkt att utgöra ett underlag till vårdprogram och framtida restaureringsinsatser.
|
|
| 17. |
|
|
| 18. |
- Brundin, Patrik, et al.
(författare)
-
Bilateral caudate and putamen grafts of embryonic mesencephalic tissue treated with lazaroids in Parkinson's disease
- 2000
-
Ingår i: Brain. - 1460-2156. ; 123, s. 1380-1390
-
Tidskriftsartikel (refereegranskat)abstract
- Five parkinsonian patients were transplanted bilaterally into the putamen and caudate nucleus with human embryonic mesencephalic tissue from between seven and nine donors. To increase graft survival, the lipid peroxidation inhibitor tirilazad mesylate was administered to the tissue before implantation and intravenously to the patients for 3 days thereafter. During the second postoperative year, the mean daily L-dopa dose was reduced by 54% and the UPDRS (Unified Parkinson's Disease Rating Scale) motor score in 'off' phase was reduced by a mean of 40%. At 10-23 months after grafting, PET showed a mean 61% increase of 6-L-[(18)F]fluorodopa uptake in the putamen, and 24% increase in the caudate nucleus, compared with preoperative values. No obvious differences in the pattern of motor recovery were observed between these and other previously studied cases with putamen grafts alone. The amount of mesencephalic tissue implanted in each putamen and caudate nucleus was 42 and 50% lower, respectively, compared with previously transplanted patients from our centre. Despite this reduction in grafted tissue, the magnitudes of symptomatic relief and graft survival were very similar. These findings suggest that tirilazad mesylate may improve survival of grafted dopamine neurons in patients, which is in agreement with observations in experimental animals.
|
|
| 19. |
- Brundin, Patrik, et al.
(författare)
-
Dopamine neurons grafted unilaterally to the nucleus accumbens affect drug-induced circling and locomotion
- 1987
-
Ingår i: Experimental Brain Research. - 0014-4819. ; 69:1, s. 183-194
-
Tidskriftsartikel (refereegranskat)abstract
- The purpose of the present study was to investigate the amplifying function of the nucleus accumbens septi region (NAS) in 6-hydroxydopamine (6-OHDA)-induced rotational behaviour by implanting fetal dopamine (DA)-rich mesencephalic cell suspensions unilaterally in the NAS of rats previously subjected to combined mesostriatal (MS) and NAS 6-OHDA lesions. First, all the rats received a unilateral 6-OHDA lesion of the ascending MS DA pathway, which produced an amphetamine-induced rotational asymmetry towards the lesioned side. In a second step, the rats received a local bilateral 6-OHDA lesion of the NAS which, as previously shown, caused a significant attenuation of the amphetamine-induced locomotor (1.5 mg/kg) and rotational (5 mg/kg) behaviour. Finally, some of these MS + NAS lesioned rats received a unilateral mesencephalic DA graft into the NAS ipsilateral to the original MS lesion. The unilateral DA-rich grafts in the NAS significantly elevated the amphetamine-induced locomotion and ipsilateral circling (opposite to the direction of rotation produced when a graft is placed in the ipsilateral caudate-putamen), suggesting that the NAS plays only an amplifier role in locomotor behaviour and not a directional role. In addition, these grafts significantly attenuated the supersensitive locomotor response observed in lesioned rats when given apomorphine (0.05 mg/kg). The findings emphasize the amplifying role of the NAS in locomotion and circling behaviour and they extend previous findings demonstrating the functional heterogeneity of the striatal complex as well as the regional specificity of the graft-derived functional effects. Moreover, the results argue against the notion that DA grafts can function through a diffusion of transmitter over large distances since, despite the large size of the grafts, the functional graft effects were well localized to the reinnervated NAS and ventromedial striatal regions. We conclude, therefore, that graft-induced amelioration of postural and locomotor deficits are affected through different parts of the striatal complex, and that multiple graft placements are required to produce more complete recovery of motoric behaviour in the DA-depleted brain.
|
|
| 20. |
- Brundin, Patrik, et al.
(författare)
-
Human fetal dopamine neurons grafted in a rat model of Parkinson's disease : immunological aspects, spontaneous and drug-induced behaviour, and dopamine release
- 1988
-
Ingår i: Experimental Brain Research. - 0014-4819. ; 70:1, s. 192-208
-
Tidskriftsartikel (refereegranskat)abstract
- We have used a rat model of Parkinson's disease (PD) to address issues of importance for a future clinical application of dopamine (DA) neuron grafting in patients with PD. Human mesencephalic DA neurons, obtained from 6.5-8 week old fetuses, were found to survive intracerebral cell suspension xenografting to the striatum of rats immunosuppressed with Cyclosporin A. The grafts produced an extensive new DA-containing terminal network in the previously denervated caudate-putamen, and they normalized amphetamine-induced, apomorphine-induced and spontaneous motor asymmetry in rats with unilateral lesions of the mesostriatal DA pathway. Grafts from an 11.5-week old donor exhibited a lower survival rate and smaller functional effects. As assessed with the intracerebral dialysis technique the grafted DA neurons were found to restore spontaneous DA release in the reinnervated host striatum to normal levels. The neurons responded with large increases in extracellular striatal DA levels after the intrastriatal administration of the DA-releasing agent d-amphetamine and the DA-reuptake blocker nomifensine, although not to the same extent as seen in striata with an intact mesostriatal DA system. DA fiber outgrowth from the grafts was dependent on the localization of the graft tissue. Thus, grafts located within the striatum gave rise to an extensive axonal network throughout the whole host striatum, whereas grafted DA neurons localized in the neocortex had their outgrowing fibers confined within the grafts themselves. In contrast to the good graft survival and behavioural effects obtained in immunosuppressed rats, there was no survival, or behavioural effects, of human DA neurons implanted in rats that did not receive immunosuppression. In addition, we found that all the graft recipients were immunized, having formed antibodies against antigens present on human T-cells. This supports the notion that the human neurons grafted to the non-immunosuppressed rats underwent immunological rejection. Based on an estimation of the survival rate and extent of fiber outgrowth from the grafted human fetal DA neurons, we suggest that DA neurons that can be obtained from one fetus may be sufficient to restore significant DA neurotransmission unilaterally, in one putamen, in an immunosuppressed PD patient.
|
|
| 21. |
|
|
| 22. |
- Finnveden, Göran, et al.
(författare)
-
Policy instruments towards a sustainable waste management
- 2013
-
Ingår i: Sustainability. - Basel : MDPI AG. - 2071-1050. ; 5:3, s. 841-881
-
Tidskriftsartikel (refereegranskat)abstract
- The aim of this paper is to suggest and discuss policy instruments that could lead towards a more sustainable waste management. The paper is based on evaluations from a large scale multi-disciplinary Swedish research program. The evaluations focus on environmental and economic impacts as well as social acceptance. The focus is on the Swedish waste management system but the results should be relevant also for other countries. Through the assessments and lessons learned during the research program we conclude that several policy instruments can be effective and possible to implement. Particularly, we put forward the following policy instruments: “Information”; “Compulsory recycling of recyclable materials”; “Weight-based waste fee in combination with information and developed recycling systems”; “Mandatory labeling of products containing hazardous chemicals”, “Advertisements on request only and other waste minimization measures”; and “Differentiated VAT and subsidies for some services”. Compulsory recycling of recyclable materials is the policy instrument that has the largest potential for decreasing the environmental impacts with the configurations studied here. The effects of the other policy instruments studied may be more limited and they typically need to be implemented in combination in order to have more significant impacts. Furthermore, policy makers need to take into account market and international aspects when implementing new instruments. In the more long term perspective, the above set of policy instruments may also need to be complemented with more transformational policy instruments that can significantly decrease the generation of waste.
|
|
| 23. |
- Finnveden, Göran, et al.
(författare)
-
Policy Instruments towards a sustainable waste management
- 2016
-
Ingår i: Solid waste management: Policy and planning for a sustainable society. - : Apple Academic Press. - 9781771883740 - 9780429091650 ; , s. 185-246, s. 185-246
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)
|
|
| 24. |
- Finnveden, Göran, 1961-, et al.
(författare)
-
Regeringen måste satsa på resurseffektivt samhälle
- 2013
-
Ingår i: Dagens nyheter. - : AB Dagens nyheter. - 1101-2447. ; :2013-04-01
-
Tidskriftsartikel (populärvet., debatt m.m.)abstract
- Regeringen förbereder en avfallspolitisk proposition. Den kommer förhoppningsvis att klargöra vem som ska ha ansvaret att samla in våra förpackningar. Men fokus borde också ligga på hur vi kan gå mot ett samhälle där resurser används så effektivt som möjligt, skriver forskare på miljöområdet.
|
|
| 25. |
- Hagell, Peter, et al.
(författare)
-
Dyskinesias following neural transplantation in Parkinson's disease.
- 2002
-
Ingår i: Nature Neuroscience. - : Springer Science and Business Media LLC. - 1546-1726 .- 1097-6256. ; 5:7, s. 627-628
-
Tidskriftsartikel (refereegranskat)abstract
- Severe dyskinesias during the 'off' phases (periods of increased Parkinson's disease (PD) disability) have been observed following intrastriatal transplantation of human embryonic mesencephalic tissue. Here we retrospectively analyzed 14 patients who were followed for up to 11 years after grafting, and found that dyskinesias (abnormal involuntary movements and postures) increased during postoperative off phases, but were generally of mild to moderate severity. Dyskinesia severity was not related to the magnitude of graft-derived dopaminergic re-innervation, as judged by (18)F-labeled 6-L-fluorodopa (FD) positron emission tomography (PET), indicating that off-phase dyskinesias probably did not result from excessive growth of grafted dopaminergic neurons.
|
|
| 26. |
- Hagell, Peter, et al.
(författare)
-
Sequential bilateral transplantation in Parkinson's disease: effects of the second graft
- 1999
-
Ingår i: Brain. - : Oxford University Press (OUP). - 1460-2156. ; 122:6, s. 1121-1132
-
Tidskriftsartikel (refereegranskat)abstract
- Five parkinsonian patients who had received implants of human embryonic mesencephalic tissue unilaterally in the striatum 10-56 months earlier were grafted with tissue from four to eight donors into the putamen (four patients) or the putamen plus the caudate nucleus (one patient) on the other side, and were followed for 18-24 months. After 12-18 months, PET showed a mean 85% increase in 6-L-[18F]fluorodopa uptake in the putamen with the second graft, whereas there was no significant further change in the previously transplanted putamen. Two patients exhibited marked additional improvements after their second graft: 'on-off' fluctuations virtually disappeared, movement speed increased, and L-dopa could be withdrawn in one patient and reduced by 70% in the other. The improvement in one patient was moderate. Two patients with atypical features, who responded poorly to the first graft, worsened following the second transplantation. These findings indicate that sequential transplantation in patients does not compromise the survival and function of either the first or the second graft. Moreover, putamen grafts that restore fluorodopa uptake to normal levels can give improvements of major therapeutic value.
|
|
| 27. |
- Hansen, Christian, et al.
(författare)
-
A novel α-synuclein-GFP mouse model displays progressive motor impairment, olfactory dysfunction and accumulation of α-synuclein-GFP.
- 2013
-
Ingår i: Neurobiology of Disease. - : Elsevier BV. - 0969-9961. ; 56C:April,30, s. 145-155
-
Tidskriftsartikel (refereegranskat)abstract
- Compelling evidence suggests that accumulation and aggregation of alpha-synuclein (α-syn) contribute to the pathogenesis of Parkinson's disease (PD). Here, we describe a novel Bacterial Artificial Chromosome (BAC) transgenic model, in which we have expressed wild-type human α-syn fused to green fluorescent protein (GFP), under control of the mouse α-syn promoter. We observed a widespread and high expression of α-syn-GFP in multiple brain regions, including the dopaminergic neurons of the substantia nigra pars compacta (SNpc) and the ventral tegmental area, the olfactory bulb as well as in neocortical neurons. With increasing age, transgenic mice exhibited reductions in amphetamine-induced locomotor activity in the open field, impaired rotarod performance and a reduced striatal dopamine release, as measured by amperometry. In addition, they progressively developed deficits in an odor discrimination test. Western blot analysis revealed that α-syn-GFP and phospho-α-syn levels increased in multiple brain regions, as the mice grew older. Further, we observed, by immunohistochemical staining for phospho-α-syn and in vivo by two-photon microscopy, the formation of α-syn aggregates as the mice aged. The latter illustrates that the model can be used to track α-syn aggregation in vivo. In summary, this novel BAC α-syn-GFP model mimics a unique set of aspects of PD progression combined with the possibility of tracking α-syn aggregation in neocortex of living mice. Therefore, this α-syn-GFP-mouse model can provide a powerful tool that will facilitate the study of α-syn biology and its involvement in PD pathogenesis.
|
|
| 28. |
- Hard, Joanna, et al.
(författare)
-
Conbase : a software for unsupervised discovery of clonal somatic mutations in single cells through read phasing
- 2019
-
Ingår i: Genome Biology. - : BMC. - 1465-6906 .- 1474-760X. ; 20
-
Tidskriftsartikel (refereegranskat)abstract
- Accurate variant calling and genotyping represent major limiting factors for downstream applications of single-cell genomics. Here, we report Conbase for the identification of somatic mutations in single-cell DNA sequencing data. Conbase leverages phased read data from multiple samples in a dataset to achieve increased confidence in somatic variant calls and genotype predictions. Comparing the performance of Conbase to three other methods, we find that Conbase performs best in terms of false discovery rate and specificity and provides superior robustness on simulated data, in vitro expanded fibroblasts and clonal lymphocyte populations isolated directly from a healthy human donor.
|
|
| 29. |
|
|
| 30. |
- Jägerskog, Ann-Sofie, 1977-, et al.
(författare)
-
Visualising the complex and the changing : Identifying critical aspects of social science models
- 2022
-
Ingår i: Earli SIG9 2022: Phenomenography and variation theory in practice. - Stockholm.
-
Konferensbidrag (refereegranskat)abstract
- Extended summaryWe live in a world that is rapidly changing and what we believe to be true today may very well be overturned tomorrow. Many of the issues raised in social studies education are characterized by changeability and complexity, such as conflicts, sustainable development, issues of justice, as well as political, social and economic processes. One common way of helping students to grasp the complex relations and the changeability involved in social studies related issues is to use models. Examples of models often used in social studies teaching are models illustrating sustainable development or political processes, as well as illustrations of the socio-economic cycle and diagrams visualizing relations between different factors in society. However, teacher experience as well as earlier research indicate that students often find it difficult to understand and interpret models (see for instance Roberts & Brugar, 2017; Jägerskog, 2020; Sundler, Dudas & Anderhag, 2017). In addition, there is a risk that these seemingly fixed models do not offer an understanding of the changeability in societal issues. The aim of this presentation is to discuss how phenomenography and variation theory (with a focus on critical aspects) can increase our understanding of how models used in social studies teaching can help students understand the complexity and changeability in societal issues. The aim is also to discuss the possible transferability of critical aspects between different kinds models used in social studies teaching. The presentation is based on a project aiming at identifying students’ understanding of two kinds of models (flowcharts and plot diagrams) often used in social studies teaching, and what students need to discern in order to develop the ability reason in a qualified way about the content illustrated. The material analysed consists of 46 recorded and transcribed small group discussions where students in year 6 and 8 in compulsory school and year 1 in upper secondary school discuss a question that concerns either a flowchart illustrating the democracy system in Sweden, a flowchart of the socio-economic cycle, a plot diagram illustrating the relationship between different countries’ GDP and level of CO2 emissions, or a plot diagram illustrating the relationship between birthrate per woman in different countries and the amount of years girls in these countries attend to school. The transcribed material was analysed using phenomenographic methods and critical aspects were identified for the four different models investigated (Marton, 2015). Results show that the critical aspects identified in part can be understood as model and content specific, but in part as model generic. This means that although two flowcharts (or two plot diagrams) illustrate different content, the aspects identified as necessary for students to discern in order to reason about the content illustrated in a qualified way, are very similar. Although similarities are especially clear between models of the same kind (i.e between two different plot diagrams or two different flowcharts), similarities can also be found between the different kinds of models (i.e between flowcharts and diagrams).This raises questions concerning the transferability of critical aspects between different kinds of models and if aspects that reoccur in relation to different models, such as aspects of changeability and complexity, could be understood as especially characteristic for social studies models. ReferencesJägerskog, A., (2020). Making possible by making visible. Learning through visual representations in social science. (Doktorsavhandling). Stockholms universitet.Marton, F. (2015). Necessary conditions of learning. Routledge.Roberts, K. L., & Brugar, K. A. (2017). The view from here: Emergence of graphical literacy. Reading Psychology, 38(8), 733-777.Sundler, M., Dudas, C. & Anderhag, P. (2017). Från missförstånd till klarhet: hur kan undervisningen organiseras för att stötta elevers förståelse för växthuseffekten? Forskning om undervisning och lärande, 5(2), 6-29.
|
|
| 31. |
- Kefalopoulou, Zinovia, et al.
(författare)
-
Long-term clinical outcome of fetal cell transplantation for Parkinson disease : two case reports
- 2014
-
Ingår i: JAMA Neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 71:1, s. 7-83
-
Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE: Recent advances in stem cell technologies have rekindled an interest in the use of cell replacement strategies for patients with Parkinson disease. This study reports the very long-term clinical outcomes of fetal cell transplantation in 2 patients with Parkinson disease. Such long-term follow-up data can usefully inform on the potential efficacy of this approach, as well as the design of trials for its further evaluation.OBSERVATIONS: Two patients received intrastriatal grafts of human fetal ventral mesencephalic tissue, rich in dopaminergic neuroblasts, as restorative treatment for their Parkinson disease. To evaluate the very long-term efficacy of the grafts, clinical assessments were performed 18 and 15 years posttransplantation. Motor improvements gained gradually over the first postoperative years were sustained up to 18 years posttransplantation, while both patients have discontinued, and remained free of any, pharmacological dopaminergic therapy.CONCLUSIONS AND RELEVANCE: The results from these 2 cases indicate that dopaminergic cell transplantation can offer very long-term symptomatic relief in patients with Parkinson disease and provide proof-of-concept support for future clinical trials using fetal or stem cell therapies.
|
|
| 32. |
- Kurowska, Zuzanna, et al.
(författare)
-
Identification of Multiple QTLs Linked to Neuropathology in the Engrailed-1 Heterozygous Mouse Model of Parkinson's Disease
- 2016
-
Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
-
Tidskriftsartikel (refereegranskat)abstract
- Motor symptoms in Parkinson's disease are attributed to degeneration of midbrain dopaminergic neurons (DNs). Heterozygosity for Engrailed-1 (En1), one of the key factors for programming and maintenance of DNs, results in a parkinsonian phenotype featuring progressive degeneration of DNs in substantia nigra pars compacta (SNpc), decreased striatal dopamine levels and swellings of nigro-striatal axons in the SwissOF1-En1+/- mouse strain. In contrast, C57Bl/6-En1+/- mice do not display this neurodegenerative phenotype, suggesting that susceptibility to En1 heterozygosity is genetically regulated. Our goal was to identify quantitative trait loci (QTLs) that regulate the susceptibility to PD-like neurodegenerative changes in response to loss of one En1 allele. We intercrossed SwissOF1-En1+/- and C57Bl/6 mice to obtain F2 mice with mixed genomes and analyzed number of DNs in SNpc and striatal axonal swellings in 120 F2-En1+/- 17 week-old male mice. Linkage analyses revealed 8 QTLs linked to number of DNs (p = 2.4e-09, variance explained = 74%), 7 QTLs linked to load of axonal swellings (p = 1.7e-12, variance explained = 80%) and 8 QTLs linked to size of axonal swellings (p = 7.0e-11, variance explained = 74%). These loci should be of prime interest for studies of susceptibility to Parkinson's disease-like damage in rodent disease models and considered in clinical association studies in PD.
|
|
| 33. |
- Larsson, Miriam, et al.
(författare)
-
Functional studies of the yeast Med5, Med15 and Med16 mediator tail subunits
- 2013
-
Ingår i: PLOS ONE. - : Public Library of Science (PLOS). - 1932-6203. ; 8:8
-
Tidskriftsartikel (refereegranskat)abstract
- The yeast Mediator complex can be divided into three modules, designated Head, Middle and Tail. Tail comprises the Med2, Med3, Med5, Med15 and Med16 protein subunits, which are all encoded by genes that are individually non-essential for viability. In cells lacking Med16, Tail is displaced from Head and Middle. However, inactivation of MED5/MED15 and MED15/MED16 are synthetically lethal, indicating that Tail performs essential functions as a separate complex even when it is not bound to Middle and Head. We have used the N-Degron method to create temperature-sensitive (ts) mutants in the Mediator tail subunits Med5, Med15 and Med16 to study the immediate effects on global gene expression when each subunit is individually inactivated, and when Med5/15 or Med15/16 are inactivated together. We identify 25 genes in each double mutant that show a significant change in expression when compared to the corresponding single mutants and to the wild type strain. Importantly, 13 of the 25 identified genes are common for both double mutants. We also find that all strains in which MED15 is inactivated show down-regulation of genes that have been identified as targets for the Ace2 transcriptional activator protein, which is important for progression through the G1 phase of the cell cycle. Supporting this observation, we demonstrate that loss of Med15 leads to a G1 arrest phenotype. Collectively, these findings provide insight into the function of the Mediator Tail module.
|
|
| 34. |
|
|
| 35. |
- Li, Jia-Yi, et al.
(författare)
-
Characterization of Lewy body pathology in 12- and 16-year-old intrastriatal mesencephalic grafts surviving in a patient with Parkinson's disease.
- 2010
-
Ingår i: Movement Disorders. - : Wiley. - 0885-3185. ; 25:8, s. 1091-1096
-
Tidskriftsartikel (refereegranskat)abstract
- We previously reported the occurrence of Lewy bodies in grafted human fetal mesencephalic neurons in two patients with Parkinson's disease. Here, we have used immunohistochemistry and electron microscopy to characterize the development of Lewy bodies in one of these cases. This patient was operated in putamen on both sides at 12 or 16 years before death, respectively. We demonstrate that 2% of the 12-year-old and 5% of the 16-year-old grafted, presumed dopaminergic neurons contained Lewy bodies immunoreactive for alpha-synuclein. Based on morphological analysis, two forms of alpha-synuclein-positive aggregates were distinguished in the grafts, the first a classical and compact Lewy body, the other a loose meshwork aggregate. Lewy bodies in the grafts stained positively for ubiquitin and thioflavin-S, and contained characteristic alpha-synuclein immunoreactive electron dense fibrillar structures on electron microscopy. Our data indicate that Lewy bodies develop gradually in transplanted dopaminergic neurons in a fashion similar to that in dopaminergic neurons in the host substantia nigra. (c) 2010 Movement Disorder Society.
|
|
| 36. |
- Li, Jia-Yi, et al.
(författare)
-
Lewy bodies in grafted neurons in subjects with Parkinson's disease suggest host-to-graft disease propagation.
- 2008
-
Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1546-170X .- 1078-8956. ; 14, s. 501-503
-
Tidskriftsartikel (refereegranskat)abstract
- Two subjects with Parkinson's disease who had long-term survival of transplanted fetal mesencephalic dopaminergic neurons (11-16 years) developed alpha-synuclein-positive Lewy bodies in grafted neurons. Our observation has key implications for understanding Parkinson's pathogenesis by providing the first evidence, to our knowledge, that the disease can propagate from host to graft cells. However, available data suggest that the majority of grafted cells are functionally unimpaired after a decade, and recipients can still experience long-term symptomatic relief.
|
|
| 37. |
- LI, WEN, et al.
(författare)
-
Extensive graft-derived dopaminergic innervation is maintained 24 years after transplantation in the degenerating parkinsonian brain.
- 2016
-
Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 113:23, s. 6544-6549
-
Tidskriftsartikel (refereegranskat)abstract
- Clinical trials using cells derived from embryonic ventral mesencephalon have shown that transplanted dopaminergic neurons can survive and function in the long term, as demonstrated by in vivo brain imaging using 18F-fluorodopa and 11C-raclopride positron emission tomography. Here we report the postmortem analysis of a patient with Parkinson’s disease who 24 y earlier underwent unilateral transplantation of embryonic dopaminergic neurons in the putamen and subsequently exhibited major motor improvement and recovery of striatal dopaminergic function. Histopathological analysis showed that a dense, near-normal graft-derived dopaminergic reinnervation of the putamen can be maintained for a quarter of a century despite severe host brain pathology and with no evidence of immune response. In addition, ubiquitin- and α-synuclein–positive inclusions were seen, some with the appearance of typical Lewy bodies, in 11–12% of the grafted dopaminergic neurons, reflecting the spread of pathology from the host brain to the transplants. Because the clinical benefits induced by transplantation in this patient were gradually lost after 14 y posttransplantation, our findings provide the first reported evidence, to our knowledge, that even a viable dopaminergic graft giving rise to extensive striatal reinnervation may lose its efficacy if widespread degenerative changes develop in the host brain.
|
|
| 38. |
- Mandel, Ronald J., et al.
(författare)
-
The Importance of Graft Placement and Task Complexity for Transplant-Induced Recovery of Simple and Complex Sensorimotor Deficits in Dopamine Denervated Rats
- 1990
-
Ingår i: European Journal of Neuroscience. - : Wiley. - 1460-9568 .- 0953-816X. ; 2:10, s. 888-894
-
Tidskriftsartikel (refereegranskat)abstract
- The present study examined the role of graft placement and behavioural task complexity in determining the functional efficacy of intrastriatal grafts of dopamine-rich fetal ventral mesencephalon (VM) placed in the dopamine (DA) depleted striatum. The functional effects of two different striatal placements of VM grafts were evaluated using tests of drug-induced motor asymmetry, simple sensorimotor orienting response, and a more complex sensorimotor integrative task (disengage behaviour), in which the rat has to perform the orienting response while in the act of eating. Rats with complete unilateral 6-hydroxydopamine (6-OHDA) lesions of the mesostriatal DA pathway, received either implants of dissociated fetal VM in the central or ventrolateral portions of the denervated striatum. Nongrafted lesioned rats served as controls. Nine weeks after grafting, the rats were tested on separate days for disengage behaviour, sensorimotor orientation, and amphetamine-induced rotational behaviour. Consistent with previous findings, the two graft placements had differential effects on drug-induced motor asymmetry and sensorimotor responses: the centrally placed VM grafts reversed amphetamine-induced rotational asymmetry but had little effect on the sensorimotor deficit, whereas the ventrolaterally placed grafts reversed the sensorimotor orientation deficits without any effect on the drug-induced rotation. In contrast, fetal VM grafts, regardless of their placement, did not ameliorate the observed deficits in disengage behaviour; that is the grafted rats that had recovered their sensorimotor response in the absence of food were unable to perform the same orienting response while eating. These results provide evidence that functional intrastriatal VM grafts which are capable of restoring sensorimotor responses or motor asymmetry fail to affect lesion-induced deficits in a task that requires more complex sensorimotor integration. It is suggested that the degree of anatomical integration of the grafted DA neurons into the host circuitry will determine the efficacy of the grafts to influence more complex sensorimotor integrative deficits in the DA lesion model.
|
|
| 39. |
- Piccini, P, et al.
(författare)
-
Delayed recovery of movement-related cortical function in Parkinson's disease after striatal dopaminergic grafts
- 2000
-
Ingår i: Annals of Neurology. - 1531-8249. ; 48:5, s. 689-695
-
Tidskriftsartikel (refereegranskat)abstract
- Intrastriatal transplantation of dopaminergic neurones aims to repair the selective loss of nigrostriatal projections and the consequent dysfunction of striatocortical circuitries in Parkinson's disease (PD). Here, we have studied the effects of bilateral human embryonic dopaminergic grafts on the movement-related activation of frontal cortical areas in 4 PD patients using H2 15O positron emission tomography and a joystick movement task. At 6.5 months after transplantation, mean striatal dopamine storage capacity as measured by 18F-dopa positron emission tomography was already significantly elevated in these patients. This was associated with a modest clinical improvement on the Unified Parkinson's Disease Rating Scale, whereas the impaired cortical activation was unchanged. At 18 months after surgery, there was further significant clinical improvement in the absence of any additional increase in striatal 18F-dopa uptake. Rostral supplementary motor and dorsal prefrontal cortical activation during performance of joystick movements had significantly improved, however. Our data suggest that the function of the graft goes beyond that of a simple dopamine delivery system and that functional integration of the grafted neurones within the host brain is necessary to produce substantial clinical recovery in PD.
|
|
| 40. |
- Piccini, P, et al.
(författare)
-
Dopamine release from nigral transplants visualized in vivo in a Parkinson's patient
- 1999
-
Ingår i: Nature Neuroscience. - : Springer Science and Business Media LLC. - 1546-1726 .- 1097-6256. ; 2:12, s. 1137-1140
-
Tidskriftsartikel (refereegranskat)abstract
- Synaptic dopamine release from embryonic nigral transplants has been monitored in the striatum of a patient with Parkinson's disease using [11C]-raclopride positron emission tomography to measure dopamine D2 receptor occupancy by the endogenous transmitter. In this patient, who had received a transplant in the right putamen 10 years earlier, grafts had restored both basal and drug-induced dopamine release to normal levels. This was associated with sustained, marked clinical benefit and normalized levels of dopamine storage in the grafted putamen. Despite an ongoing disease process, grafted neurons can thus continue for a decade to store and release dopamine and give rise to substantial symptomatic relief.
|
|
| 41. |
- Sandahl, Johan, 1974-, et al.
(författare)
-
Överdrivna slutsatser om gymnasieelevers demokratikunskaper
- 2022
-
Ingår i: Skola & Samhälle [S.O.S] Webbtidskrift. - : Föreningen Skola & Samhälle - webbtidskrift. - 2001-6727.
-
Tidskriftsartikel (populärvet., debatt m.m.)abstract
- Rapporten från Stiftelsen Rättsfonden om gymnasieelevers kunskaper om demokrati har både metodologiska och teoretiska brister. Eftersom rapporten saknar stöd för flera av de rekommendationer som lämnas är risken att föreslagna förändringar inte gör någon skillnad eller i värsta fall leder i fel riktning, skriver Johan Sandahl med flera, alla forskare i samhällsvetenskapernas didaktik.
|
|
| 42. |
- Tväråna, Malin, 1974-, et al.
(författare)
-
Att utmana bilden av systemet : elever läser visualiseringar av samhällssystem
- 2024
-
Ingår i: Nordidactica. - : Karlstads universitet. - 2000-9879. ; 14:1, s. 112-138
-
Tidskriftsartikel (refereegranskat)abstract
- Visuella modeller används i samhällskunskap för att beskriva centrala samhällssystem och strukturer som hör till ämnets kanon. Samtidigt saknas kunskap om elevers förmåga att läsa och använda dessa representationer. I studien undersöktes hur elever på mellanstadiet, högstadiet och gymnasiet förstod två olika flödesscheman över det samhällsekonomiska kretsloppet och det demokratiska systemet. 22 transkriberade gruppsamtal analyserades med hjälp av fenomenografi och variationsteori. Kritiska aspekter som identifierades rör urskiljandet av flödesschemat som en helhet snarare än många delar, att se relationerna mellan modellens enheter som ömsesidiga, att förstå att det representerade systemet är konstruerat och inte naturgivet samt att urskilja att det representerade systemet står i relation till externa faktorer. Resultaten utgör didaktiska utgångspunkter för undervisning som utvecklar elevers förmåga att läsa och använda modeller i diskussioner om komplexa samhällssystem.
|
|
| 43. |
- Tväråna, Malin, 1974-, et al.
(författare)
-
Att utmana bilden av systemet - elever läser visualiseringar av samhällssystem
- 2024
-
Ingår i: Nordidactica. - : Karlstads universitet. - 2000-9879. ; 14:1, s. 112-138
-
Tidskriftsartikel (refereegranskat)abstract
- Visuella modeller används i samhällskunskap för att beskriva centrala samhällssystem och strukturer som hör till ämnets kanon. Samtidigt saknas kunskap om elevers förmåga att läsa och använda dessa representationer. I studien undersöktes hur elever på mellanstadiet, högstadiet och gymnasiet förstod två olika flödesscheman över det samhällsekonomiska kretsloppet och det demokratiska systemet. 22 transkriberade gruppsamtal analyserades med hjälp av fenomenografi och variationsteori. Kritiska aspekter som identifierades rör urskiljandet av flödesschemat som en helhet snarare än många delar, att se relationerna mellan modellens enheter som ömsesidiga, att förstå att det representerade systemet är konstruerat och inte naturgivet samt att urskilja att det representerade systemet står i relation till externa faktorer. Resultaten utgör didaktiska utgångspunkter för undervisning som utvecklar elevers förmåga att läsa och använda modeller i diskussioner om komplexa samhällssystem.
|
|
| 44. |
|
|
| 45. |
- Tväråna, Malin, 1974-, et al.
(författare)
-
Vad möjliggör modellen? : Elevers förståelse av visuella modeller i samhällskunskap.
- 2021
-
Konferensbidrag (refereegranskat)abstract
- Många viktiga samhällsfrågor om försörjning, kulturmöten, klimatutmaningar och ekonomiska, sociala och politiska processer utmärks av komplexa relationer och samband som kan vara svåra att få grepp om. I skolans samhällskunskapsundervisning används ofta visuella representationer för att illustrera och förtydliga samband inom denna typ av samhällsfrågor. Såväl lärares erfarenheter som tidigare forskning (till exempel Roberts & Brugar, 2017; Sundler, Dudas & Anderhag, 2017) visar dock att elever ofta har svårt att tolka och förstå de visuella representationer som används i undervisningen. Elever riskerar att gå miste om stora, ofta centrala, delar av innehållet (Jägerskog, 2020), i både läromedel och i nyhetsflöden och andra media, vilket utgör ett stort problem i relation till skolans och samhällskunskapsämnets medborgarbildande uppdrag. Denna studie ingår i projektet ”Säger bilden mer än tusen ord?” och syftar till att utveckla kunskap om elevers förståelse av två visuella representationer, flödesscheman och plotdiagram, som ofta används i samhällskunskapsundervisning, och om vad elever behöver urskilja för att kunna utveckla en mer kvalificerad förmåga att läsa dessa visuella modeller över olika ämnesinnehåll.I studien har elever i årskurs 6, 8 och år 1 på gymnasiet genomfört korta diskussionsuppgifter som spelats in och analyserats med hjälp av fenomenografi (Marton 2015). Uppgifterna behandlade antingen ett flödesscheman över det parlamentariska systemet, ett flödesschema över det samhällsekonomiska systemet, ett plot-diagram som beskriver relationen mellan olika länders medelinkomst och nivå av CO2-utsläpp eller ett plotdiagram som beskriver relationen mellan olika länders nativitet och utbildningsnivå hos flickor. Såväl uppgiftsdesign som analys av materialet har involverat hela projektgruppen. Den fenomenografiska analysen möjliggör identifiering av vad som behöver synliggöras i undervisning där modellerna används, men inte en analys av undervisningspraktiken. Detta fokuseras istället i forskningsprojektets senare skede, då resultatet från denna kartläggningsstudie kommer att användas för att pröva och undersöka undervisning i en learning study (Carlgren, Eriksson & Runesson 2017).Resultatet av studien beskriver ett antal aspekter av ett flödesschema som förefaller vara kritiska för elever att urskilja om de ska kunna läsa flödesschemat som en modell av ett samhällsvetenskapligt system, som det parlamentariska respektive det samhällsekonomiska systemet. Dessa är (i) att flödesschemat representerar en helhet snarare än ett antal enskilda enheter, (ii) att relationerna mellan de olika enheterna i flödesschemat är ömsesidiga, (iii) att det representerade systemet inte är naturgivet utan konstituerat av mänskliga handlingar samt (iv) att det representerade systemet står i relation till externa faktorer. Vissa av dessa aspekter framstår som svårare att få syn på i relation till vissa ämnesinnehåll (specifika samhällssystem). Aspekter som på motsvarande sätt är kritiska för att elever ska kunna läsa plotdiagram som en modell över relationen mellan samhällsfaktorer (som medelinkomst och nivå av CO2-utsläpp eller nativitet och flickors utbildningsnivå) är (i) det övergripande mönstret hos den representerade relationen, (ii) att detta mönster inte är konstant utan generellt, och (iii) att mönstret behöver relateras till faktorer utanför de som finns för att kunna diskuteras.Resultaten är relevanta för samhällskunskapslärare på flera olika skolstadier och den kunskap som utvecklas genom projektet kan i förlängningen användas av lärare för att planera, genomföra och utvärdera sin undervisning.
|
|
| 46. |
- Tväråna, Malin, et al.
(författare)
-
Visualising complexity and changeability - critical aspects of teaching visual models in economics
- 2023
-
Ingår i: EARLI 2023. - Leuven : European Association for Research on Learning and Instruction (EARLI). ; , s. 104-104
-
Konferensbidrag (refereegranskat)abstract
- The aim of this presentation is to discuss how models used in social studies teaching can help students grasp the complexity and changeability in economic issues and systems in the context of social science education (SSE). Models are often used in SSE teaching to help students grasp complexity and changeability. However, students often find models difficult to understand and there is a risk that seemingly fixed models do not offer an understanding of the changeability in societal issues. The project investigates students’ conceptions of two different models that are commonly used in SSE (one flowchart and one plot diagram) and what aspects that need to be discerned in order for students to reason in a qualified way about the content illustrated. Results from a phenomenographic analysis of 21 group discussions (with students from both compulsory and upper secondary school) show that the critical aspects identified in part can be understood as model and content specific, but in part as model generic. By comparing the critical aspects for the two different models, it is evident that in order to read both models, aspects pertaining to structure, casual expansion, and human agency are important.
|
|
| 47. |
- von Malmborg, Fredrik, 1971-, et al.
(författare)
-
Improving energy efficiency of buildings
- 2023
-
Ingår i: Handbook on climate change and technology. - Cheltenham : Edward Elgar Publishing. - 9781800882119 ; , s. 163-178
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)
|
|
| 48. |
- Wenning, Gregor K, et al.
(författare)
-
Short- and long-term survival and function of unilateral intrastriatal dopaminergic grafts in Parkinson's disease
- 1997
-
Ingår i: Annals of Neurology. - : Wiley. - 1531-8249 .- 0364-5134. ; 42:1, s. 95-107
-
Tidskriftsartikel (refereegranskat)abstract
- Six patients with Parkinson's disease were followed for 10 to 72 months after human embryonic mesencephalic tissue from four to seven donors was grafted unilaterally into the putamen (4 patients) or putamen plus caudate (2 patients). After 8 to 12 months, positron emission tomography showed a 68% increase of 6-L-[18F]-fluorodopa uptake in the grafted putamen, no change in the grafted caudate, and minor decreases in nongrafted striatal regions. There was therapeutically valuable improvement in 4 patients, but only modest changes in the other 2, both of whom developed atypical features. Patient 4 was without L-dopa from 32 months and had normal fluorodopa uptake in the grafted putamen at 72 months. Overall, the L-dopa dose was reduced by a mean of 10 and 20%, "off" time was reduced by 34 and 44%, and the "off" phase Unified Parkinson's Disease Rating Scale motor score by 18 and 26%, and the duration of the response to a single L-dopa dose increased by 45 and 58% during the first and second years after surgery, respectively. Rigidity and hypokinesia improved bilaterally, but mainly contralateral to the implant. No consistent changes in dyskinesias were observed. We conclude that transplantation of embryonic mesencephalic tissue leads to highly reproducible survival of dopaminergic neurons, inducing clinically valuable improvements in most recipients.
|
|
| 49. |
- Widner, H, et al.
(författare)
-
Bilateral fetal mesencephalic grafting in two patients with parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)
- 1992
-
Ingår i: New England Journal of Medicine. - 0028-4793. ; 327:22, s. 63-1556
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Intracerebral transplantation of fetal dopaminergic neurons is a promising new approach for the treatment of Parkinson's disease. Patients with parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) have a relatively stable lesion limited to the nigrostriatal system, rendering them ideal candidates for transplantation. Improvement of motor function after neural grafting has previously been observed in nonhuman primates with MPTP-induced parkinsonism.METHODS: We grafted human fetal tissue from the ventral mesencephalon (obtained six to eight weeks after conception) bilaterally to the caudate and putamen in two immunosuppressed patients with severe MPTP-induced parkinsonism, using a stereotaxic technique. The patients were assessed regularly with clinical rating scales, timed tests of motor performance, and [18F]fluorodopa positron-emission tomography during the 18 months before the operation and the 22 to 24 months after the operation.RESULTS: Both patients had substantial, sustained improvement in motor function and became much more independent. Postoperatively, the second patient's maintenance dose of levodopa was decreased to 150 mg daily, which was 30 percent of the original dose. Striatal uptake of fluorodopa was unchanged 5 to 6 months postoperatively but was markedly and bilaterally increased at 12 to 13 and 22 to 24 months in both patients, closely paralleling the patients' clinical improvement. There were no serious complications.CONCLUSIONS: Bilateral implantation of fetal mesencephalic tissue can induce substantial long-term functional improvement in patients with parkinsonism and severe dopamine depletion and is accompanied by increased uptake of fluorodopa by the striatum. The results in these patients resemble those obtained in MPTP-treated primates and suggest that this will be a useful model for the assessment of transplantation therapies in Parkinson's disease.
|
|
| 50. |
|
|
