| 1. |
- Jonsson, Andreas P., et al.
(författare)
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Disulphide-reduced superoxide dismutase-1 in CNS of transgenic amyotrophic lateral sclerosis models
- 2006
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Ingår i: Brain. - : Oxford University Press. - 0006-8950 .- 1460-2156. ; 129:Pt 2, s. 451-644
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Tidskriftsartikel (refereegranskat)abstract
- Mutant forms of superoxide dismutase-1 (SOD1) cause amyotrophic lateral sclerosis (ALS) by an unknown noxious mechanism. Using an antibody against a novel epitope in the G127insTGGG mutation, mutant SOD1 was studied for the first time in spinal cord and brain of an ALS patient. The level was below 0.5% of the SOD1 level in controls. In corresponding transgenic mice the content of mutant SOD1 was also low, although it was enriched in spinal cord and brain compared with other tissues. In the mice the misfolded mutant SOD1 aggregated rapidly and 20% occurred in steady state as detergent-soluble protoaggregates. The misfolded SOD1 and the protoaggregates form, from birth until death, a potentially noxious burden that may induce the motor neuron injury. Detergent-resistant aggregates, as well as inclusions of mutant SOD1 in motor neurons and astrocytes, accumulated in spinal cord ventral horns of the patient and mice with terminal disease. The inclusions and aggregates may serve as terminal markers of long-term assault by misfolded SOD1 and protoaggregates.
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| 2. |
- Norrhem, Bosse, et al.
(författare)
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Security Arena, årsrapport 2008
- 2009
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- *** Allmänt ***För beskrivning av Security Arena Lindholmens övergripande verksamhet och organisation, samt definitioner av ett antal begrepp, se kapitlet Inledning.*** Inriktning på forskning och utveckling ***Konceptgenerering, pilotprojekt och studieuppdrag har bedrivits inom de temaområden som definierades i samband med att avtalet mellan Lindholmen Science Park (LSP) och Krisberedskapsmyndigheten (KBM) tecknades 2007. De definierade temaområdena är Samhällskritiska transporter,Mobilt bredband för säkerhet i samhället, Surveillance and Early Warning samt Metoder och system för säker och robust krishantering.Fokus inom temaprojekten har i år legat på farligt godstransporter, hamnsäkerhet, användning av kommersiella nät för samhällssäkerhet, samt teknik för avvikelsedetektering. Inom forskningstemat, Metoder och system för säker och robust krishantering, bedrivs fortsatt arbete i fem olika delprojekt.Ett antal nya experter har under året tillförts de befintliga expertgrupperna. Expertgrupperna har vidintervjutillfällen och under workshops aktivt bidragit med sin kunskap och problemformuleringar och därmed skapat relevanta förutsättningar för den forskning, koncept och pilotprojekt som utvecklats inom respektive temaprojekt.Under året har Security Arenas arbetsmodell med tidig användarmedverkan i forskning och konceptgenerering utvecklats vidare. Resultaten från arbetet visar tydligt att det via behovsanalyser med aktiv medverkan från områdesexperter går att utveckla relevanta koncept som i ett nästa steg leder till praktiska prov tillsammans med användargrupper.Förutom detta har en fördjupad marknadsutvecklingsanalys genomförts som en fortsättning på förra årets studie på samma tema.*** Samordning och samverkan ***Flera nya samarbeten som initierades under 2007 har vidareutvecklats under 2008. I maj genomfördes en gemensam övning med svensk och amerikansk medverkan inom området Maritime Domain Awareness (MDA) på Lindholmen Science Park. Övningen leddes av KBM och DHS och föregicks av ett planeringsarbete i en svensk planeringsgrupp, där också representanter från Security Arena Lindholmen ingick.I samarbete mellan Försvarsmakten, NATO, FMV och KBM genomfördes teknikexperimentet Quickwins under september 2008. Syftet var att visa på nya tekniska möjligheter till samverkan mellan civilt och militärt utvecklade system. Security Arena Lindholmen bidrog med ett antal tjänster utvecklade inom temaprojekten, samt genom att bygga upp en fiktiv ledningsplats där representanter från polis, räddningstjänst och SOS Alarm ledde verksamhet och medverkade under experimentet. Experimentet tilldrog sig stort intresse och förevisades för drygt 600 personer.Under året har även Security Arena Lindholmen, det europeiska CBRNE-centret i Umeå och Region Skåne träffats för att utveckla samarbetsmöjligheter. Vid första tillfället deltog även en representant för Linköpings universitet. Ambitionen är att utveckla och, om intresse finns, utökadetta nätverk under 2009. Nätverket har hittills resulterat i ett konkret projektsamarbete mellan Security Arena Lindholmen och CBRNE-centret.*** Kunskapsutveckling och informationsspridning ***Två saker har tydligt bidragit till kunskapsutveckling under 2008. Det ena är den ökade mängden projekt och samarbeten som inneburit att ett större antal deltagare och användare fått praktiska erfarenheter av vårt arbete. Speciellt gäller detta de pilotprojekt och det experiment vi genomfört.Förutom forskare och industrirepresentanter har närmare 100 områdesexperter och slutanvändare medverkat.Det andra är de nationella och internationella konferenser och seminarier som medarbetare inom Security Arena Lindholmen deltagit i. Bland andra kan nämnas seminarierna i samband med Quickwins-experimentet i Enköping i september, ITS 2008 i New York i november och ett större antal vetenskapliga konferenser och workshops. Dessutom har en rad presentationer genomförts för besökare på Lindholmen.*** Inriktning 2009 ***Planeringen av 2009 års arbete skall göras i nära samarbete med den nya myndigheten, Myndigheten för samhällsskydd och beredskap (MSB). Inriktningen är att de definieradetemaområdena ligger fast. Inom respektive temaområde skall relevanta projekt påbörjas. Under 2009 är det även viktigt att tillsammans med MSB utforma en lämplig fortsättning på Security Arena Lindholmens arbete.
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| 3. |
- Andersson, Henrik, et al.
(författare)
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Bullervärden för samhällsekonomisk analys : beräkningar för väg- och järnvägsbuller
- 2009
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Noise is a significant social problem. For example, more than 20 per cent of the European Union's population is exposed to higher noise than what is considered acceptable. The transport sector is a major contributor to society's increasing noise problem, due to increased traffic volumes and urbanization exposing more people to noise. Road traffic is admittedly the largest individual noise source in the transport sector, but other transport modes such as aircraft and railways are also responsible for considerable noise emissions. Noise entails costs for the society. This fact, and that society has different needs, means that policies and projects to reduce noise levels need to be evaluated to secure an efficient resource allocation. Benefit cost analysis is a powerful tool to evaluate noise abatement, but it requires both benefits and costs to be measured in a common metric, i.e. in monetary values. Today's official monetary values for all modes are based on the impact of road-traffic noise on property prices. It is a well established fact that the disturbance which individuals experience differs between modes, and therefore there is a need to estimate monetary values based on the respective modes. This report focuses on road and rail noise, two noise sources with different characteristics. This study describes the need to revise the current official Swedish policy values for noise abatement. Current values for road-traffic noise show a progressive relationship between the social cost and the noise level that is too strong, and values for railway noise has been missing and instead based on results for road noise. Valuation of health effects should also be based on EKM since it is sanctioned within the EU, instead of the approach now proposed by ASEK based on estimated total social costs from noise exposure in relation to estimates from willingness to pay studies.
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| 4. |
- Andersson, Henrik, et al.
(författare)
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Property prices and exposure to multiple noise sources : hedonic regression with road and railway noise
- 2008
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- This study examines the effect of road and railway noise on property prices. It uses the hedonic regression technique on a Swedish data set that contains information about both road and railway noise for each property, and finds that road noise has a larger negative impact on the property prices than railway noise. This is in line with the evidence from the acoustical literature which has shown that individuals are more disturbed by road than railway noise, but contradicts recent results from a hedonic study on data of the United Kingdom.
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| 5. |
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| 6. |
- Byström, Roberth, 1971-
(författare)
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SOD1´s Law : An Investigation of ALS Provoking Properties in SOD1
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Proteins are the most important molecules in the cell since they take care of most of the biological functions which resemble life. To ensure that everything is working properly the cell has a rigorous control system to monitor the proper function of its proteins and sends old or dysfunctional proteins for degradation. Unfortunately, this system sometimes fails and the once so vital proteins start to misbehave or to accumulate and in the worst case scenario these undesired processes cause the death of their host. One example is Amyotrophic Lateral Sclerosis (ALS); a progressive and always fatal neurodegenerative disorder that is proposed to derive from accumulation of aberrant proteins. Over 140 mutations in the human gene encoding the cytosolic homodimeric enzyme Cu/Zn-Superoxide Dismutase (SOD1) are linked to ALS. The key event in SOD1 associated ALS seems to be the pathological formation of toxic protein aggregates as a result of initially unfolded or partly structured SOD1-mutants. Here, we have compared the folding behaviour of a set of ALS associated SOD1 mutants. Based on our findings we propose that SOD1 mediated ALS can be triggered by a decrease in protein stability but also by mutations which reduce the net charge of the protein. Both findings are in good agreement with the hypothesis for protein aggregation. SOD1 has also been found to be able to interact with mitochondrial membranes and SOD1 inclusions have been detected in the inter-membrane space of mitochondria originating from the spinal cord. The obvious question then arose; does the misfolding and aggregation of SOD1 involve erroneous interactions with membranes? Here, we could show that there is an electrostatically driven interaction between the reduced apo SOD1 protein including ALS associated SOD1-mutants and charged lipid membrane surfaces. This association process changes the secondary structures of these mutants in a way quite different from the situation found in membrane free aqueous environment. However, the result show that mutants interact with charged lipid vesicles to lesser extent than wildtype SOD1. This opposes the correlation between decreased SOD1 stability and disease progression. We therefore suggest that the observed interaction is not a primary cause in the ALS mechanism.
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| 7. |
- Dahlgren, Markus, et al.
(författare)
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Design, Synthesis, and Multivariate Quantitative Structure-Activity Relationship of Salicylanilides-Potent Inhibitors of Type III Secretion in Yersinia
- 2007
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Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 50:24, s. 6177-6188
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Tidskriftsartikel (refereegranskat)abstract
- Analogues to the salicylanilide N-(4-Chlorophenyl)-2-acetoxy-3,5-diiodobenzamide, 1a, an inhibitor of type III secretion (T3S) in Yersinia, were selected, synthesized, and biologically evaluated in three cycles. First, a set of analogues with variations in the salicylic acid ring moiety was synthesized to probe possible structural variation. A basic structure-activity relationship was established and then used to cherry-pick compounds from a principal component analysis score plot of salicylanilides to generate a second set. A third set with increased likelihood of biological activity was designed using D-optimal onion design. A quantitative structure-activity relationship model using hierarchical partial least-square regression to latent structures (Hi-PLS) was computed using PLS score vectors of building blocks correlated to the % inhibition of T3S as a response. A PLS discriminant analysis (PLS-DA) model was derived using the same descriptor set as that for the Hi-PLS model. Both models were validated with an external test set.
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| 8. |
- Dahlin, Andreas, 1980, et al.
(författare)
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High-Resolution Microspectroscopy of Plasmonic Nanostructures for Miniaturized Biosensing
- 2009
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Ingår i: Analytical Chemistry. - : American Chemical Society. - 0003-2700 .- 1520-6882. ; 81:16, s. 6572-6580
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Tidskriftsartikel (refereegranskat)abstract
- In this article, we demonstrate how to perform microscale spectroscopy of plasmonic nanostructures in order to minimize the noise when determining the resonance peak wavelength. This is accomplished using an experimental setup containing standard optical components mounted on an ordinary light microscope. We present a detailed comparison between extinction spectroscopy in transmission mode and scattering spectroscopy under dark field illumination, which shows that extinction measurements provide higher signal-to-noise in almost all situations. Furthermore, it is shown that rational selection of nanostructure, hardware components, and data analysis algorithms enables tracking of the particle plasmon resonance wavelength from a 10 mu m x 50 mu m area with a resolution of 10(-3) nm in transmission mode. We investigate how the temporal resolution, which can be improved down to 17 Ins, affects, the noise characteristics. In addition, we show how data can be acquired from an area as small as 2 mu m x 10 mu m (similar to 240 particles) at the expense of higher noise on longer time scales. In comparison with previous work on macroscopic sensor designs, this represents a sensor miniaturization of 5 orders of magnitude, without any loss in signal-to-noise performance. As a model system, we illustrate biomolecular detection using gold nanodisks prepared by colloidal lithography. The microextinction measurements of nanodisks described here provide detection of protein surface coverages as low as 40 pg/cm(2) (less than0.1% of saturated binding). In fact, the miniaturized system provides a detection limit in terms of surface coverage comparable to state of the art macroscopic sensors, while simultaneously being as close to single protein molecule detection as sensors based on a single nanoparticle.
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| 9. |
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| 10. |
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