| 1. |
- Abel, I, et al.
(författare)
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Overview of the JET results with the ITER-like wall
- 2013
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 53:10, s. 104002-
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Tidskriftsartikel (refereegranskat)abstract
- Following the completion in May 2011 of the shutdown for the installation of the beryllium wall and the tungsten divertor, the first set of JET campaigns have addressed the investigation of the retention properties and the development of operational scenarios with the new plasma-facing materials. The large reduction in the carbon content (more than a factor ten) led to a much lower Z(eff) (1.2-1.4) during L- and H-mode plasmas, and radiation during the burn-through phase of the plasma initiation with the consequence that breakdown failures are almost absent. Gas balance experiments have shown that the fuel retention rate with the new wall is substantially reduced with respect to the C wall. The re-establishment of the baseline H-mode and hybrid scenarios compatible with the new wall has required an optimization of the control of metallic impurity sources and heat loads. Stable type-I ELMy H-mode regimes with H-98,H-y2 close to 1 and beta(N) similar to 1.6 have been achieved using gas injection. ELM frequency is a key factor for the control of the metallic impurity accumulation. Pedestal temperatures tend to be lower with the new wall, leading to reduced confinement, but nitrogen seeding restores high pedestal temperatures and confinement. Compared with the carbon wall, major disruptions with the new wall show a lower radiated power and a slower current quench. The higher heat loads on Be wall plasma-facing components due to lower radiation made the routine use of massive gas injection for disruption mitigation essential.
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| 2. |
- Romanelli, F, et al.
(författare)
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Overview of the JET results
- 2011
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 51:9
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Tidskriftsartikel (refereegranskat)abstract
- Since the last IAEA Conference JET has been in operation for one year with a programmatic focus on the qualification of ITER operating scenarios, the consolidation of ITER design choices and preparation for plasma operation with the ITER-like wall presently being installed in JET. Good progress has been achieved, including stationary ELMy H-mode operation at 4.5 MA. The high confinement hybrid scenario has been extended to high triangularity, lower ρ*and to pulse lengths comparable to the resistive time. The steady-state scenario has also been extended to lower ρ*and ν*and optimized to simultaneously achieve, under stationary conditions, ITER-like values of all other relevant normalized parameters. A dedicated helium campaign has allowed key aspects of plasma control and H-mode operation for the ITER non-activated phase to be evaluated. Effective sawtooth control by fast ions has been demonstrated with3He minority ICRH, a scenario with negligible minority current drive. Edge localized mode (ELM) control studies using external n = 1 and n = 2 perturbation fields have found a resonance effect in ELM frequency for specific q95values. Complete ELM suppression has, however, not been observed, even with an edge Chirikov parameter larger than 1. Pellet ELM pacing has been demonstrated and the minimum pellet size needed to trigger an ELM has been estimated. For both natural and mitigated ELMs a broadening of the divertor ELM-wetted area with increasing ELM size has been found. In disruption studies with massive gas injection up to 50% of the thermal energy could be radiated before, and 20% during, the thermal quench. Halo currents could be reduced by 60% and, using argon/deuterium and neon/deuterium gas mixtures, runaway electron generation could be avoided. Most objectives of the ITER-like ICRH antenna have been demonstrated; matching with closely packed straps, ELM resilience, scattering matrix arc detection and operation at high power density (6.2 MW m-2) and antenna strap voltages (42 kV). Coupling measurements are in very good agreement with TOPICA modelling. © 2011 IAEA, Vienna.
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| 3. |
- Bergman, Åke, et al.
(författare)
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Science and policy on endocrine disrupters must not be mixed : a reply to a "common sense" intervention by toxicology journal editors
- 2013
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Ingår i: Environmental Health. - : BioMed Central (BMC). - 1476-069X. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- The "common sense" intervention by toxicology journal editors regarding proposed European Union endocrine disrupter regulations ignores scientific evidence and well-established principles of chemical risk assessment. In this commentary, endocrine disrupter experts express their concerns about a recently published, and is in our considered opinion inaccurate and factually incorrect, editorial that has appeared in several journals in toxicology. Some of the shortcomings of the editorial are discussed in detail. We call for a better founded scientific debate which may help to overcome a polarisation of views detrimental to reaching a consensus about scientific foundations for endocrine disrupter regulation in the EU.
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| 4. |
- Andersson, Evelyn, et al.
(författare)
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Genetic Polymorphisms in Monoamine Systems and Outcome of Cognitive Behavior Therapy for Social Anxiety Disorder
- 2013
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:11
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveThe role of genetics for predicting the response to cognitive behavior therapy (CBT) for social anxiety disorder (SAD) has only been studied in one previous investigation. The serotonin transporter (5-HTTLPR), the catechol-o-methyltransferase (COMT) val158met, and the tryptophan hydroxylase-2 (TPH2) G-703Tpolymorphisms are implicated in the regulation of amygdala reactivity and fear extinction and therefore might be of relevance for CBT outcome. The aim of the present study was to investigate if these three gene variants predicted response to CBT in a large sample of SAD patients.MethodParticipants were recruited from two separate randomized controlled CBT trials (trial 1: n = 112, trial 2: n = 202). Genotyping were performed on DNA extracted from blood or saliva samples. Effects were analyzed at follow-up (6 or 12 months after treatment) for both groups and for each group separately at post-treatment. The main outcome measure was the Liebowitz Social Anxiety Scale Self-Report.ResultsAt long-term follow-up, there was no effect of any genotype, or gene × gene interactions, on treatment response. In the subsamples, there was time by genotype interaction effects indicating an influence of the TPH2 G-703T-polymorphism on CBT short-term response, however the direction of the effect was not consistent across trials.ConclusionsNone of the three gene variants, 5-HTTLPR, COMTval158met and TPH2 G-703T, was associated with long-term response to CBT for SAD.
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| 5. |
- Andersson, Kent, 1967-, et al.
(författare)
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Förstudie angående DTAG-metodik
- 2010
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Rapport (populärvet., debatt m.m.)abstract
- Rapporten utgör slutrapport på FMV beställning ”förstudie angående DTAG-metodik”.RTO har genomfört en studie för att utröna hur NATO bäst identifierar och nyttjar eller skyddar sig mot potentialen i s.k. ”Disruptive Technology”, d.v.s. teknologi som på kort tid signifikant förändrar genomförandet av operationer. Sverige har medverkat i studien. Den tillämpning av metoden DTAG (Disruptive Technology Assessment Games) som beskrivs i RTO studierapport är utvecklad till stöd för beslutsfattning på lång sikt, d.v.s. avseende FoT, konceptutveckling, förbandsutveckling- och materielplanering. Idén bakom den här förstudien är emellertid att undersöka möjligheterna att överföra metoden till erfarenhetsanalys och planering i ett kortare tidsperspektiv - med bibehållande av de rapporterade positiva effekterna för erfarenhetsutbytet mellan personal inom försvarsfamiljen av alla kategorier.Rapporten inleds med en diskussion och beskrivning av möjliga anpassningar av DTAG för den nya föreslagna tillämpningen. Slutsatsen är att metoden har potential att effektivt återkoppla speldeltagarnas erfarenheter från uppdrag de deltagit i - dels från egen användning av tekniska system och dels från andra aktörers teknologi - till utvecklingen av de materielsystem som bedöms vara i drift inom en tidsperiod av ca fem år. En analys av identifierade styrkor, svagheter, möjligheter och risker leder sedan fram till ett förslag till implementering av metoden och förslag till fortsatt arbete. En positiv bieffekt med att arrangera en återkommande DTAG-aktivitet inom ramen för FHS, i samarbete med FMV och FM, är t.ex. en förbättrad erfarenhetsöverspridning till utbildningen av officerare.Förstudien rekommenderar en studie till FHS under 2011 med uppgifterna att:pröva och uppdatera metodramverket till förstudiens DTAG-tillämpningplanera och genomföra prov och försök med bemanning enl. förstudiens förslag till organisationgenomföra en litteraturstudie och utvärdera den tillämpade DTAG-metodenmed andra relevanta metoder och deras tillämpningar avseende: erfarenhetsåtermatning,konceptval och scenariebaserad analys, även i andra domäner än den militära.rapportera skriftligen med rekommendation om implementering av metoden i produktionsledningen av materielprocessen – inkl. lämpliga årliga återkommande tidpunkter för genomförande, m.h.t. rotationer och årliga avvägningar i materielplanen.Ett förslag till organisation, aktivitetsplan och en uppskattning av kostnaderna presenteras.
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| 6. |
- Andersson, Lisa, et al.
(författare)
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Mutations in DMRT3 affect locomotion in horses and spinal circuit function in mice
- 2012
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 488:7413, s. 642-646
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Tidskriftsartikel (refereegranskat)abstract
- Locomotion in mammals relies on a central pattern-generating circuitry of spinal interneurons established during development that coordinates limb movement(1). These networks produce left-right alternation of limbs as well as coordinated activation of flexor and extensor muscles(2). Here we show that a premature stop codon in the DMRT3 gene has a major effect on the pattern of locomotion in horses. The mutation is permissive for the ability to perform alternate gaits and has a favourable effect on harness racing performance. Examination of wild-type and Dmrt3-null mice demonstrates that Dmrt3 is expressed in the dI6 subdivision of spinal cord neurons, takes part in neuronal specification within this subdivision, and is critical for the normal development of a coordinated locomotor network controlling limb movements. Our discovery positions Dmrt3 in a pivotal role for configuring the spinal circuits controlling stride in vertebrates. The DMRT3 mutation has had a major effect on the diversification of the domestic horse, as the altered gait characteristics of a number of breeds apparently require this mutation.
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| 7. |
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| 8. |
- Andersson, Mattias, et al.
(författare)
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A 7.5 mW 9 MHz CT Delta-Sigma Modulator in 65 nm CMOS with 69 dB SNDR and Reduced Sensitivity to Loop Delay Variations
- 2012
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Ingår i: IEEE Asian Solid State Circuits Conference (A-SSCC), 2012. ; , s. 245-248
-
Konferensbidrag (refereegranskat)abstract
- This paper presents a 3rd-order, 3-bit continuous time (CT) Delta-Sigma modulator for an LTE radio receiver. By adopting a return-to-zero (RZ) pulse in the innermost DAC, the modulator shows a reduced sensitivity to loop-delay variations, and the additional loop delay compensation usually needed in CT modulators can be omitted. The modulator has been implemented in a 65nm CMOS process, where it occupies an area of 0.2mmx0.4mm. It achieves an SNR of 71dB and an SNDR of 69dB over a 9MHz bandwidth with an oversampling ratio of 16. Power consumption is 7.5mW from a 1.2V supply, for a figure-of-merit of 181fJ/conversion.
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| 9. |
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| 10. |
- Andersson, Mattias, et al.
(författare)
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A Filtering Delta Sigma ADC for LTE and Beyond
- 2014
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Ingår i: IEEE Journal of Solid-State Circuits. - 0018-9200. ; 49:7, s. 1535-1547
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Tidskriftsartikel (refereegranskat)abstract
- Abstract in UndeterminedThis paper presents a filtering ADC for the LTE communication standard, where a second-order Delta-Sigma modulator (DSM) is incorporated into the third-order Chebychev channel-select filter (CSF) of the radio receiver. The CSF introduces an additional third-order suppression of both thermal and quantization DSM noise, while the CSF transfer function is maintained. A design method for the filtering ADC accounting for unavoidable DSM-DAC delays is developed and experimentally demonstrated. The 65 nm CMOS prototype is clocked at 576/288 MHz with an 18.5/9.0 MHz LTE bandwidth, has an in-band gain of 26 dB, an SNDR of 56.4/58.1 dB, an input-referred noise of 5 nV/root Hz, and an out-of-band (half-duplex) IIP3 of 20/12 dBV(rms), with a power consumption of 7.9/5.4 mW and an overall state-of-the art performance.
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| 11. |
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| 12. |
- Andersson, Martin, et al.
(författare)
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Open or Delete : Decision-makers’ Attitudes Toward E-mail Marketing Messages
- 2014
-
Ingår i: Advances in Social Sciences Research Journal. - : Scholar Publishing. - 2055-0286. ; 1:3, s. 133-144
-
Tidskriftsartikel (refereegranskat)abstract
- Organisations make use of e-mail marketing messages, with Swedish companies spending SEK40 million on this form of marketing communication. The purpose of this paper was to examine the attitudes of decision-makers in the Swedish manufacturing industry regarding e-mail marketing messages received.The authors used a quantitative research approach with an online-survey in order to collect the necessary data. The population was decision-makers within the manufacturing industry in Sweden and 1 777 responses from decision-makers were received and analysed.The majority of decision-makers tend to have negative attitudes toward e-mail marketing messages. Differences in attitudes exist between those of different ages and positions within companies. While respondents indicated that they check their e-mail frequently, no significant differences in attitudes to e-mail marketing messages could be identified. Marketers can attempt to improve attitudes among recipients by building relationships with the recipients prior to sending e-mail marketing messages, and paying attention to the layout and content of the e-mails.
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| 13. |
- Andersson, Martin, et al.
(författare)
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The opening of the North-South divide: Cumulative causation, household income disparity and the regional bonus in Taiwan 1976-2005
- 2012
-
Ingår i: Structural Change and Economic Dynamics. - : Elsevier BV. - 0954-349X .- 1873-6017. ; 23:2, s. 170-179
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Tidskriftsartikel (refereegranskat)abstract
- During the last decades regional income divergence seems to have reappeared in both developed and developing countries. In Taiwan – a renowned case of growth with equity – regional per capita income was converging until the early 1990s after which it began to diverge. With the help of modeled annual household survey data from 1976 to 2005 we indicate the magnitude of a regional bonus and discuss reasons behind the re-opening of the North-South income divide in Taiwan. Our analysis suggests that this process is a consequence of cumulative causation connected to the advent of the rise of ICT industry in conjunction with changes in Taiwan’s political economy which provided relatively more advantageous economic opportunities for the industrial structure of the leading region.
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| 14. |
- Andersson, Mattias, et al.
(författare)
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Theory and Design of a CT Delta Sigma Modulator with Low Sensitivity to Loop-Delay Variations
- 2013
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Ingår i: Analog Integrated Circuits and Signal Processing. - : Springer Science and Business Media LLC. - 0925-1030 .- 1573-1979. ; 76:3, s. 353-366
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Tidskriftsartikel (refereegranskat)abstract
- This paper presents a 3rd-order, 3-bit continuous-time (CT) \Updelta\Upsigma Δ Σ modulator for an LTE radio receiver. A return-to-zero (RZ) pulse, centered in the sampling period by a quadrature clock, is used in the innermost DAC to reduce the sensitivity to loop-delay variations in the modulator, and omit implementing the additional loop delay compensation usually needed in CT modulators. The performance and stability of the NRZ/NRZ/RZ feedback scheme is thoroughly analysed using a discrete-time model. The modulator has been implemented in a 65 nm CMOS process, where it occupies an area of 0.2 × 0.4 mm2. It achieves an SNR of 71 dB and an SNDR of 69 dB over a 9 MHz bandwidth with an oversampling ratio of 16, and a power consumption of 7.5 mW from a 1.2 V supply.
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| 15. |
- Axberg, Stefan, et al.
(författare)
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Lärobok i Militärteknik, vol. 9 : Teori och metod
- 2013. - 1
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Bok (övrigt vetenskapligt/konstnärligt)abstract
- Ämnet militärteknik utgår från att tekniska system är officerens arbetsredskap och att en förståelse för och kunskap om dessa verktyg är central för att kunna utöva professionen framgångsrikt. Denna nionde volym av Lärobok i Militärteknik, benämnd Teori och Metod, behandlar centrala begrepp, teorier och postulat samt metoder för värdering av teknik och består av ett antal texter författade av 16 forskare och lärare vid den militärtekniska avdelningen. Volymen riktar sig främst till de som inlett sin officersutbildning och utgörs till stora delar av ett kompilat av publicerade och opublicerade militärtekniska texter och kan sägas utgöra militärteknikens ”state of the art”.
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| 16. |
- Chapman, Henry N, et al.
(författare)
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Femtosecond X-ray protein nanocrystallography.
- 2011
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 470:7332, s. 73-7
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Tidskriftsartikel (refereegranskat)abstract
- X-ray crystallography provides the vast majority of macromolecular structures, but the success of the method relies on growing crystals of sufficient size. In conventional measurements, the necessary increase in X-ray dose to record data from crystals that are too small leads to extensive damage before a diffraction signal can be recorded. It is particularly challenging to obtain large, well-diffracting crystals of membrane proteins, for which fewer than 300 unique structures have been determined despite their importance in all living cells. Here we present a method for structure determination where single-crystal X-ray diffraction 'snapshots' are collected from a fully hydrated stream of nanocrystals using femtosecond pulses from a hard-X-ray free-electron laser, the Linac Coherent Light Source. We prove this concept with nanocrystals of photosystem I, one of the largest membrane protein complexes. More than 3,000,000 diffraction patterns were collected in this study, and a three-dimensional data set was assembled from individual photosystem I nanocrystals (∼200nm to 2μm in size). We mitigate the problem of radiation damage in crystallography by using pulses briefer than the timescale of most damage processes. This offers a new approach to structure determination of macromolecules that do not yield crystals of sufficient size for studies using conventional radiation sources or are particularly sensitive to radiation damage.
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| 17. |
- Crosby, Jacy, et al.
(författare)
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Loss-of-Function Mutations in APOC3, Triglycerides, and Coronary Disease
- 2014
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 371:1, s. 22-31
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Tidskriftsartikel (refereegranskat)abstract
- Background Plasma triglyceride levels are heritable and are correlated with the risk of coronary heart disease. Sequencing of the protein-coding regions of the human genome (the exome) has the potential to identify rare mutations that have a large effect on phenotype. Methods We sequenced the protein-coding regions of 18,666 genes in each of 3734 participants of European or African ancestry in the Exome Sequencing Project. We conducted tests to determine whether rare mutations in coding sequence, individually or in aggregate within a gene, were associated with plasma triglyceride levels. For mutations associated with triglyceride levels, we subsequently evaluated their association with the risk of coronary heart disease in 110,970 persons. Results An aggregate of rare mutations in the gene encoding apolipoprotein C3 (APOC3) was associated with lower plasma triglyceride levels. Among the four mutations that drove this result, three were loss-of-function mutations: a nonsense mutation (R19X) and two splice-site mutations (IVS2+1G -> A and IVS3+1G -> T). The fourth was a missense mutation (A43T). Approximately 1 in 150 persons in the study was a heterozygous carrier of at least one of these four mutations. Triglyceride levels in the carriers were 39% lower than levels in noncarriers (P<1x10(-20)), and circulating levels of APOC3 in carriers were 46% lower than levels in noncarriers (P = 8x10(-10)). The risk of coronary heart disease among 498 carriers of any rare APOC3 mutation was 40% lower than the risk among 110,472 noncarriers (odds ratio, 0.60; 95% confidence interval, 0.47 to 0.75; P = 4x10(-6)). Conclusions Rare mutations that disrupt APOC3 function were associated with lower levels of plasma triglycerides and APOC3. Carriers of these mutations were found to have a reduced risk of coronary heart disease. (Funded by the National Heart, Lung, and Blood Institute and others.)
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| 18. |
- Dey, Anil, et al.
(författare)
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Laboratory instructions as a cause of student dissonance
- 2010
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Ingår i: [Host publication title missing].
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Konferensbidrag (refereegranskat)abstract
- Improving the quality of education is the goal of all pedagogical research. By using student surveys and course evaluations problem areas can be identified in most courses offered by universities. In this paper we perform a large-scale student survey in order to find the causes of, and remedies to, a widespread student dissonance in a mandatory course with over 100 students at Lund University. Our research shows that aiming for deeper learning, without providing time and a stimulating environment, can be worse than settling for expository learning. This problem has persisted for years despite attempts by the course administrators to solve the problem. We propose that major improvements can be achieved, both in learning and pass rates, primarily by improving the lab instructions but also by using a more intellectually stimulating lab equipment.
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| 19. |
- Ederle, Joerg, et al.
(författare)
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Carotid artery stenting compared with endarterectomy in patients with symptomatic carotid stenosis (International Carotid Stenting Study): an interim analysis of a randomised controlled trial
- 2010
-
Ingår i: The Lancet. - 1474-547X. ; 375:9719, s. 985-997
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Tidskriftsartikel (refereegranskat)abstract
- Background Stents are an alternative treatment to carotid endarterectomy for symptomatic carotid stenosis, but previous trials have not established equivalent safety and efficacy. We compared the safety of carotid artery stenting with that of carotid endarterectomy. Methods The International Carotid Stenting Study (ICSS) is a multicentre, international, randomised controlled trial with blinded adjudication of outcomes. Patients with recently symptomatic carotid artery stenosis were randomly assigned in a 1:1 ratio to receive carotid artery stenting or carotid endarterectomy. Randomisation was by telephone call or fax to a central computerised service and was stratified by centre with minimisation for sex, age, contralateral occlusion, and side of the randomised artery. Patients and investigators were not masked to treatment assignment. Patients were followed up by independent clinicians not directly involved in delivering the randomised treatment. The primary outcome measure of the trial is the 3-year rate of fatal or disabling stroke in any territory, which has not been analysed yet. The main outcome measure for the interim safety analysis was the 120-day rate of stroke, death, or procedural myocardial infarction. Analysis was by intention to treat (ITT). This study is registered, number ISRCTN25337470. Findings The trial enrolled 1713 patients (stenting group, n=855; endarterectomy group, n=858). Two patients in the stenting group and one in the endarterectomy group withdrew immediately after randomisation, and were not included in the ITT analysis. Between randomisation and 120 days, there were 34 (Kaplan-Meier estimate 4.0%) events of disabling stroke or death in the stenting group compared with 27 (3.2%) events in the endarterectomy group (hazard ratio [HR] 1.28, 95% CI 0.77-2.11). The incidence of stroke, death, or procedural myocardial infarction was 8.5% in the stenting group compared with 5.2% in the endarterectomy group (72 vs 44 events; HR 1.69, 1.16-2.45, p=0.006), Risks of any stroke (65 vs 35 events; HR 1.92, 1.27-2.89) and all-cause death (19 vs seven events; HR 2.76, 1.16-6.56) were higher in the stenting group than in the endarterectomy group. Three procedural myocardial infarctions were recorded in the stenting group, all of which were fatal, compared with four, all non-fatal, in the endarterectomy group. There was one event of cranial nerve palsy in the stenting group compared with 45 in the endarterectomy group. There were also fewer haematomas of any severity in the stenting group than in the endarterectomy group (31 vs 50 events; p=0.0197). Interpretation Completion of long-term follow-up is needed to establish the efficacy of carotid artery stenting compared with endarterectomy. In the meantime, carotid endarterectomy should remain the treatment of choice for patients suitable for surgery.
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| 20. |
- Hantke, Max F., et al.
(författare)
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High-throughput imaging of heterogeneous cell organelles with an X-ray laser
- 2014
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Ingår i: Nature Photonics. - : Springer Science and Business Media LLC. - 1749-4885 .- 1749-4893. ; 8:12, s. 943-949
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Tidskriftsartikel (refereegranskat)abstract
- We overcome two of the most daunting challenges in single-particle diffractive imaging: collecting many high-quality diffraction patterns on a small amount of sample and separating components from mixed samples. We demonstrate this on carboxysomes, which are polyhedral cell organelles that vary in size and facilitate up to 40% of Earth's carbon fixation. A new aerosol sample-injector allowed us to record 70,000 low-noise diffraction patterns in 12 min with the Linac Coherent Light Source running at 120 Hz. We separate different structures directly from the diffraction data and show that the size distribution is preserved during sample delivery. We automate phase retrieval and avoid reconstruction artefacts caused by missing modes. We attain the highest-resolution reconstructions on the smallest single biological objects imaged with an X-ray laser to date. These advances lay the foundations for accurate, high-throughput structure determination by flash-diffractive imaging and offer a means to study structure and structural heterogeneity in biology and elsewhere.
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| 21. |
- Hasse, Dirk, et al.
(författare)
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Structure of the Homodimeric Glycine Decarboxylase P-protein from Synechocystis sp PCC 6803 Suggests a Mechanism for Redox Regulation
- 2013
-
Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 288:49, s. 35333-35345
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Tidskriftsartikel (refereegranskat)abstract
- Glycine decarboxylase, or P-protein, is a pyridoxal 5-phosphate (PLP)-dependent enzyme in one-carbon metabolism of all organisms, in the glycine and serine catabolism of vertebrates, and in the photorespiratory pathway of oxygenic phototrophs. P-protein from the cyanobacterium Synechocystis sp. PCC 6803 is an (2) homodimer with high homology to eukaryotic P-proteins. The crystal structure of the apoenzyme shows the C terminus locked in a closed conformation by a disulfide bond between Cys(972) in the C terminus and Cys(353) located in the active site. The presence of the disulfide bridge isolates the active site from solvent and hinders the binding of PLP and glycine in the active site. Variants produced by substitution of Cys(972) and Cys(353) by Ser using site-directed mutagenesis have distinctly lower specific activities, supporting the crucial role of these highly conserved redox-sensitive amino acid residues for P-protein activity. Reduction of the 353-972 disulfide releases the C terminus and allows access to the active site. PLP and the substrate glycine bind in the active site of this reduced enzyme and appear to cause further conformational changes involving a flexible surface loop. The observation of the disulfide bond that acts to stabilize the closed form suggests a molecular mechanism for the redox-dependent activation of glycine decarboxylase observed earlier.
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| 22. |
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| 23. |
- Knappe, Christoph, et al.
(författare)
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Thickness dependent variations in surface phosphor thermometry during transient combustion in an HCCI engine
- 2013
-
Ingår i: Combustion and Flame. - : Elsevier BV. - 0010-2180. ; 160:8, s. 1466-1475
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Tidskriftsartikel (refereegranskat)abstract
- Phosphor thermometry is a semi-invasive measurement technique which is commonly used for temperature determination in combustion applications. Surface temperature measurements using thermographic phosphors rely on the assumption that the phosphor layer is thin enough in order to adopt the surface temperature non-intrusively. This work compares the temperature information, recorded from two opposing sides of phosphor films, coated on a translucent part of the combustion chamber wall inside a car engine. The film thickness was varied between 5 and 72 mu m and two different phosphors were studied; CdWO4 and La2O2S:Eu. For both phosphors, the results showed no significant differences. Being subject to unsteady heat transfer during fired engine operation, phosphor coatings above 20 mu m in thickness experienced a significant temperature gradient between the front- and the backside of the coating, whereas thinner layers did not seem to be affected within the limits of measurement accuracy and precision. Cycle-to-cycle variations of the global gas temperature were not found to correlate with phosphor temperature variations. However, a strong temperature correlation between opposite sides of the phosphor coating was observed for film thicknesses below 20 mu m during engine cycle-to-cycle variations. (C) 2013 The Combustion Institute. Published by Elsevier Inc. All rights reserved.
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| 24. |
- Liu, Meng, 1976, et al.
(författare)
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Targeting the protein prenyltransferases efficiently reduces tumor development in mice with K-RAS-induced lung cancer
- 2010
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 107:14, s. 6471-6476
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Tidskriftsartikel (refereegranskat)abstract
- RAS and RHO proteins, which contribute to tumorigenesis and metastasis, undergo posttranslational modification with an isoprenyl lipid by protein farnesyltransferase (FTase) or protein geranylgeranyltransferase-I (GGTase-I). Inhibitors of FTase and GGTase-I were developed to block RAS-induced malignancies, but their utility has been difficult to evaluate because of off-target effects, drug resistance, and toxicity. Moreover, the impact of FTase deficiency and combined FTase/GGTase-I deficiency has not been evaluated with genetic approaches. We found that inactivation of FTase eliminated farnesylation of HDJ2 and H-RAS, prevented H-RAS targeting to the plasma membrane, and blocked proliferation of primary and K-RAS(G12D)-expressing fibroblasts. FTase inactivation in mice with K-RAS-induced lung cancer reduced tumor growth and improved survival, similar to results obtained previously with inactivation of GGTase-I. Simultaneous inactivation of FTase and GGTase-I markedly reduced lung tumors and improved survival without apparent pulmonary toxicity. These data shed light on the biochemical and therapeutic importance of FTase and suggest that simultaneous inhibition of FTase and GGTase-I could be useful in cancer therapeutics.
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| 25. |
- Lundberg, Martin, et al.
(författare)
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Multiplexed Homogeneous Proximity Ligation Assays for High-throughput Protein Biomarker Research in Serological Material
- 2011
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Ingår i: Molecular & Cellular Proteomics. - 1535-9476 .- 1535-9484. ; 10:4, s. M110.004978-
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Tidskriftsartikel (refereegranskat)abstract
- A high throughput protein biomarker discovery tool has been developed based on multiplexed proximity ligation assays in a homogeneous format in the sense of no washing steps. The platform consists of four 24-plex panels profiling 74 putative biomarkers with sub-pM sensitivity each consuming only 1 mu l of human plasma sample. The system uses either matched monoclonal antibody pairs or the more readily available single batches of affinity purified polyclonal antibodies to generate the target specific reagents by covalently linking with unique nucleic acid sequences. These paired sequences are united by DNA ligation upon simultaneous target binding forming a PCR amplicon. Multiplex proximity ligation assays thereby converts multiple target analytes into real-time PCR amplicons that are individually quantified using microfluidic high capacity qPCR in nano liter volumes. The assay shows excellent specificity, even in multiplex, by its dual recognition feature, its proximity requirement, and most importantly by using unique sequence specific reporter fragments on both antibody-based probes. To illustrate the potential of this protein detection technology, a pilot biomarker research project was performed using biobanked plasma samples for the detection of colorectal cancer using a multivariate signature.
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