| 1. |
- Alerstam, Thomas, et al.
(författare)
-
Flight speeds among bird species : allometric and phylogenetic effects.
- 2007
-
Ingår i: PLoS biology. - : Public Library of Science (PLoS). - 1544-9173 .- 1545-7885. ; 5:8, s. e197-
-
Tidskriftsartikel (refereegranskat)abstract
- Flight speed is expected to increase with mass and wing loading among flying animals and aircraft for fundamental aerodynamic reasons. Assuming geometrical and dynamical similarity, cruising flight speed is predicted to vary as (body mass)(1/6) and (wing loading)(1/2) among bird species. To test these scaling rules and the general importance of mass and wing loading for bird flight speeds, we used tracking radar to measure flapping flight speeds of individuals or flocks of migrating birds visually identified to species as well as their altitude and winds at the altitudes where the birds were flying. Equivalent airspeeds (airspeeds corrected to sea level air density, Ue) of 138 species, ranging 0.01-10 kg in mass, were analysed in relation to biometry and phylogeny. Scaling exponents in relation to mass and wing loading were significantly smaller than predicted (about 0.12 and 0.32, respectively, with similar results for analyses based on species and independent phylogenetic contrasts). These low scaling exponents may be the result of evolutionary restrictions on bird flight-speed range, counteracting too slow flight speeds among species with low wing loading and too fast speeds among species with high wing loading. This compression of speed range is partly attained through geometric differences, with aspect ratio showing a positive relationship with body mass and wing loading, but additional factors are required to fully explain the small scaling exponent of Ue in relation to wing loading. Furthermore, mass and wing loading accounted for only a limited proportion of the variation in Ue. Phylogeny was a powerful factor, in combination with wing loading, to account for the variation in Ue. These results demonstrate that functional flight adaptations and constraints associated with different evolutionary lineages have an important influence on cruising flapping flight speed that goes beyond the general aerodynamic scaling effects of mass and wing loading.
|
|
| 2. |
- Berthet, Pierre, et al.
(författare)
-
Functional Relevance of Different Basal Ganglia Pathways Investigated in a Spiking Model with Reward Dependent Plasticity
- 2016
-
Ingår i: Frontiers in Neural Circuits. - : FRONTIERS MEDIA SA. - 1662-5110. ; 10
-
Tidskriftsartikel (refereegranskat)abstract
- The brain enables animals to behaviorally adapt in order to survive in a complex and dynamic environment, but how reward-oriented behaviors are achieved and computed by its underlying neural circuitry is an open question. To address this concern, we have developed a spiking model of the basal ganglia (BG) that learns to dis-inhibit the action leading to a reward despite ongoing changes in the reward schedule. The architecture of the network features the two pathways commonly described in BG, the direct (denoted D1) and the indirect (denoted D2) pathway, as well as a loop involving striatum and the dopaminergic system. The activity of these dopaminergic neurons conveys the reward prediction error (RPE), which determines the magnitude of synaptic plasticity within the different pathways. All plastic connections implement a versatile four-factor learning rule derived from Bayesian inference that depends upon pre- and post-synaptic activity, receptor type, and dopamine level. Synaptic weight updates occur in the D1 or D2 pathways depending on the sign of the RPE, and an efference copy informs upstream nuclei about the action selected. We demonstrate successful performance of the system in a multiple-choice learning task with a transiently changing reward schedule. We simulate lesioning of the various pathways and show that a condition without the D2 pathway fares worse than one without D1. Additionally, we simulate the degeneration observed in Parkinson's disease (PD) by decreasing the number of dopaminergic neurons during learning. The results suggest that the D1 pathway impairment in PD might have been overlooked. Furthermore, an analysis of the alterations in the synaptic weights shows that using the absolute reward value instead of the RPE leads to a larger change in D1.
|
|
| 3. |
|
|
| 4. |
- Brandi, Maya, et al.
(författare)
-
Multiscale modeling through MUSIC multi-simulation : Modeling a dendritic spine using MOOSE and NeuroRD
- 2011
-
Ingår i: Front. Neuroinform. Conference Abstract. - : Frontiers Media SA.
-
Konferensbidrag (refereegranskat)abstract
- The nervous system encompasses structure and phenomena at different spatial and temporal scales from molecule to behavior. In addition, different scales are described by different physical and mathematical formalisms. The dynamics of second messenger pathways can be formulated as stochastic reaction-diffusion systems [1] while the electrical dynamics of the neuronal membrane is often described by compartment models and the Hodgkin-Huxley formalism. In neuroscience, there is an increasing need and interest to study multi-scale phenomena where multiple scales and physical formalisms are covered by a single model. While there exists simulators/frameworks, such as GENESIS and MOOSE [3], which span such scales (kinetikit/HH-models), most software applications are specialized for a given domain. Here, we report about initial steps towards a framework for multi-scale modeling which builds on the concept of multi-simulations [2]. We aim to provide a standard API and communication framework allowing parallel simulators targeted at different scales and/or different physics to communicate on-line in a cluster environment. Specifically, we show prototype work on simulating the effect on receptor induced cascades on membrane excitability. Electrical properties of a compartment model is simulated in MOOSE, while receptor induced cascades are simulated in NeuroRD [4,7] . In a prototype system, the two simulators are connected using PyMOOSE [5] and JPype [6]. The two models with their different physical properties (membrane currents in MOOSE, molecular biophysics in NeuroRD), are joined into a single model system. We demonstrate the interaction of the numerical solvers of two simulators (MOOSE, NeuroRD) targeted at different spatiotemporal scales and different physics while solving a multi-scale problem. We analyze some of the problems that may arise in multi-scale multi-simulations and present requirements for a generic API for parallel solvers. This work represents initial steps towards a flexible modular framework for simulation of large-scale multi-scale multi-physics problems in neuroscience. References 1. Blackwell KT: An efficient stochastic diffusion algorithm for modeling second messengers in dendrites and spines. J Neurosci Meth 2006, 157: 142-153. 2. Djurfeldt M, Hjorth J, Eppler JM, Dudani N, Helias M, Potjans TC, Bhalla US, Diesmann M, Hellgren Kotaleski J, Ekeberg Ö: Run-Time Interoperability Between Neural Network Simulators Based on the MUSIC Framework. Neurinform 2010, 8: 43-60. 3. Dudani N, Ray S, George S, Bhalla US: Multiscale modeling and interoperability in MOOSE. Neuroscience 2009, 10(Suppl 1): 54. 4. Oliveira RF, Terrin A, Di Benedetto G, Cannon RC, Koh W, Kim M, Zaccolo M, Blacwell KT: The Role of Type 4 Phosphdiesterases in Generating Microdomains of cAMP: Large Scale Stochastic Simulations.
|
|
| 5. |
- Djurfeldt, Mikael, 1967-, et al.
(författare)
-
Run-Time Interoperability Between Neuronal Network Simulators Based on the MUSIC Framework
- 2010
-
Ingår i: Neuroinformatics. - : Springer Science and Business Media LLC. - 1539-2791 .- 1559-0089. ; 8:1, s. 43-60
-
Tidskriftsartikel (refereegranskat)abstract
- MUSIC is an API allowing large scale neuron simulators using MPI internally to exchange data during runtime. We provide experiences from the adaptation of two neuronal network simulators of different kinds, NEST and MOOSE, to this API. A multi-simulation of a cortico-striatal network model involving both simulators is performed, demonstrating how MUSIC can promote inter-operability between models written for different simulators and how these can be re-used to build a larger model system. We conclude that MUSIC fulfills the design goals of being portable and simple to adapt to existing simulators. In addition, since the MUSIC API enforces independence between the applications, the multi-simulationcould be built from pluggable component modules without adaptation of the components to each other in terms of simulation time-step or topology of connections between the modules.
|
|
| 6. |
- Ejhed, Helene, et al.
(författare)
-
Belastning och påverkan från dagvatten : Källor till föroreningar i dagvatten, potentiell effekt, och jämförelser med belastning från andra källor
- 2018
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- SMED har på uppdrag av Naturvårdsverket tagit fram denna rapport om föroreningar och belastning från dagvatten. Studien är en del av ett Regeringsuppdrag ”Föreslå etappmål om dagvatten”. Syftet med projektet har varit att ta fram en sammanställning om belastning av föroreningar från dagvatten till vattenrecipienter. Primära källor, potentiella toxiska och hormonstörande effekter samt belastning på ytvatten har sammanställts och beräknats av ett urval av prioriterade ämnen och Särskilda Förorenande Ämnen (SFÄ) och omfattande sammanlagt 22 st näringsämnen, metaller och organiska miljöföroreningar. Dessa ämnen valdes ut eftersom de är kända ämnen i dagvatten, prioriterade ämnen av Vattenmyndigheterna på grund av att de orsakar att god kemisk eller ekologisk status inte uppnås i många vattenförekomster samt att det var möjligt att göra beräkningar av belastning av dessa tack vare att det fanns data tillgängligt. Dessa 22 ämnen har sådana ekologiska, toxiska och/eller hormonstörande effekter i akvatisk miljö att belastningen av samtliga av dessa ämnen bör begränsas eller helt förhindras. Dagvattnets påverkan och effekter på miljön har sammanställts utifrån tillgänglig litteratur. Studierna är dock få och av varierande karaktär, vilket gör det svårt att dra några generella slutsatser gällande dagvattnet påverkan.Antalet föroreningar i dagvatten kan dock vara många fler än de 22 utvalda ämnena. Uppmätta halter i dagvatten har sammanställts från Naturvårdsverkets Screeningdatabas i denna rapport och visar att 74 st ämnen förekommer i samtliga prover av dagvatten där de har analyserats, och ytterligare 117 st ämnen förekommer i en del av dagvattenproverna. Många är ämnen som ännu inte är prioriterade av vattenförvaltningen. Bland annat förekommer ofta metaller och grundämnen, vissa dioxiner och furaner, alkylfenoler, antioxidanter, bekämpningsmedel, kolväten, LAS (Linear alkyl benzene sulfonate) och olika flamskyddsmedel. Resultat av belastningsberäkningarna visar att dagvatten är en betydande spridningsväg till belastningen i recipienter för vissa ämnen trots att arealen tätort är mindre än 1% av Sveriges totala yta. För metallerna kadmium, zink, bly och koppar så har bidragen från dagvatten beräknats till mellan 15% och 17% av den totala belastningen till recipienter i Sverige och kan anses vara betydande belastning. I mellan 451 och 1090 st enskilda vattenförekomstområden är belastningen från dagvatten den dominerande spridningsvägen (>50% av total belastning) till de olika metallerna. Dagvatten utgör 100% av belastningen i 17 st vattenförekomster för koppar, zink och bly, i 12 st vattenförekomster för kadmium och nickel och i enbart 3 st vattenförekomster för kvicksilver. För de organiska ämnena är uppgifterna om utsläpp väldigt osäkra eller saknas helt för många källor till total belastning i Sverige, så som läckage från olika marktyper, jordbruksmark och skog, men de tillgängliga data och beräkningarna som gjorts indikerar att dagvatten utgör en viktig spridningsväg för PAH16, DEHP, Nonylfenol, HCH, TBT, PBDE, PFOS och PCB7 till vattenrecipienter.Betydande bidrag (>25%) till belastningen i dagvatten kommer ifrån mark inom tätorter som används till ”industri, handelsplats, grus- och sandtag, hamn och deponiverksamhet” för samtliga metaller, för nonylfenol (58%), PFOS (54%), PAH16 (40%), HCH (23%), PCB7 (23%), PBDE (22%) och oktylfenol (18%). Industri och handelsplats utgör den största arealen inom den markanvändningsklassen och bör prioriteras i det fortsatta arbetet. Industri och handelsplatser har höga typhalter och höga avrinningskoefficienter som orsakar den höga belastningen. Belastningen i dagvatten av ftalaten DEHP kommer däremot till största del ifrån ytor av ”enstaka hus, mycket grönyta” (35%), ”bostadsområde, mindre grönyta” (29%) samt ”urbant grönområde, idrottsanläggning, flygfält gräs” (25%). Markanvändningsklassen ”enstaka hus, mycket grönyta” utgör den största arealen totalt inom tätorter i Sverige (35% av arean), vilket innebär att den ytan bidrar med generellt stor belastning.Det finns stora osäkerheter i resultaten beroende bland annat på brist på mätningar av ämnen i dagvatten. Beräkningarna i denna rapport baseras på markanvändning som sammanställts av SMED till HELCOM Pollution Load Compilation (PLC7) rapporteringen, typhalter och avrinningskoefficienter inom tätorter från Stormtac databasen samt rapporterade utsläpp i miljörapporter från avloppsreningsverk och industrier i Svenska Miljörapporteringsportalen. Framförallt för organiska ämnen är dataunderlaget litet, vilket gör dessa uppskattningar mer osäkra. Utökad miljöövervakning av metaller och organiska ämnen behövs för att kunna följa trender och sätta in rätt åtgärder uppströms vid källorna och nedströms genom rening av dagvatten.Det stora antalet ämnen som har uppmätts i dagvatten och den betydande belastningen som dagvatten har beräknats bidra med, indikerar trots osäkerheterna på att miljöproblemen med dagvatten kan vara omfattande. Påverkan i form av eventuella överskridanden av miljökvalitetsnormer i recipienterna har inte kunnat beräknas inom ramen för detta projekt.
|
|
| 7. |
- Eriksson, Mikael, et al.
(författare)
-
Low-Dose Tamoxifen for Mammographic Density Reduction : A Randomized Controlled Trial
- 2021
-
Ingår i: Journal of Clinical Oncology. - 0732-183X. ; 39:17, s. 1899-
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Tamoxifen prevents breast cancer in high-risk women and reduces mortality in the adjuvant setting. Mammographic density change is a proxy for tamoxifen therapy response. We tested whether lower doses of tamoxifen were noninferior to reduce mammographic density and associated with fewer symptoms.PATIENTS AND METHODS: Women, 40-74 years of age, participating in the Swedish mammography screening program were invited to the 6-month double-blind six-arm randomized placebo-controlled noninferiority dose-determination KARISMA phase II trial stratified by menopausal status (EudraCT 2016-000882-22). In all, 1,439 women were accrued with 1,230 participants accessible for intention-to-treat analysis. The primary outcome was proportion of women treated with placebo, 1, 2.5, 5, and 10 mg whose mammographic density decreased at least as much as the median reduction in the 20 mg arm. The noninferior margin was 17%. Secondary outcome was reduction of symptoms. Post hoc analyses were performed by menopausal status. Per-protocol population and full population were analyzed in sensitivity analysis.RESULTS: The 1,439 participants, 566 and 873 pre- and postmenopausal women, respectively, were recruited between October 1, 2016, and September 30, 2019. The participants had noninferior mammographic density reduction following 2.5, 5, and 10 mg tamoxifen compared with the median 10.1% decrease observed in the 20 mg group, a reduction confined to premenopausal women. Severe vasomotor symptoms (hot flashes, cold sweats, and night sweats) were reduced by approximately 50% in the 2.5, 5, and 10 mg groups compared with the 20 mg group.CONCLUSION: Premenopausal women showed noninferior magnitude of breast density decrease at 2.5 mg of tamoxifen, but fewer side effects compared with the standard dose of 20 mg. Future studies should test whether 2.5 mg of tamoxifen reduces the risk of primary breast cancer.
|
|
| 8. |
- Hellgren, Mikael, et al.
(författare)
-
Efficiency of an AC Conductive In-Road Charging System for Electric Vehicles-Analysis of Pilot Project Data
- 2020
-
Ingår i: SAE International Journal of Alternative Powertrains. - : SAE International. - 2167-4191 .- 2167-4205 .- 2691-3747. ; 9:1
-
Tidskriftsartikel (refereegranskat)abstract
- This article describes the conductive in-road charging system as developed in the eRoadArlanda project, a pilot project for the development of in-road charging system for both heavy and light vehicles intended for application in motorways. The results of an analysis of measurements collected during the integration tests of this system are presented and discussed. The results focus on the end-to-end efficiency of the in-road charging system and aim to provide researchers in the field with a reference for this technology and configuration for use in the future development of such infrastructure. The analysis of the measurement data addresses losses in the low-voltage side of the AC conductive charging system as well as the vehicle-mounted isolated rectifier/converter connected to the vehicle DC system. An exploratory analysis of data collected over a 6-month testing period in varying weather conditions is used to provide insight into factors affecting the overall efficiency of the system. A discussion of the results includes the effects of cable dimensioning, rectifier performance and placement, and the use of salt for deicing.
|
|
| 9. |
- Huss, Mikael, et al.
(författare)
-
An experimentally constrained computational model of NMDA oscillations in lamprey CPG neurons
- 2008
-
Ingår i: Journal of Computational Neuroscience. - : Springer Science and Business Media LLC. - 0929-5313 .- 1573-6873. ; 15:1, s. 108-121
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Rhythmicity is a characteristic of neural networks responsible for locomotion. In many organisms, activation of N-methyl-D-aspartate (NMDA) receptors leads to generation of rhythmic locomotor patterns. In addition, single neurons can display intrinsic, NMDA-dependent membrane potential oscillations when pharmacologically isolated from each other by tetrodotoxin (TTX) application. Such NMDA-TTX oscillations have been characterized, for instance, in lamprey locomotor network neurons. Conceptual and computational models have been put forward to explain the appearance and characteristics of these oscillations. Here, we seek to refine the understanding of NMDA-TTX oscillations by combining new experimental evidence with computational modelling. We find that, in contrast to previous computational predictions, the oscillation frequency tends to increase when the NMDA concentration is increased. We develop a new, minimal computational model which can incorporate this new information. This model is further constrained by another new piece of experimental evidence: that regular-looking NMDA-TTX oscillations can be obtained even after voltage-dependent potassium and high-voltage-activated calcium channels have been pharmacologically blocked. Our model conforms to several experimentally derived criteria that we have set up and is robust to parameter changes, as evaluated through sensitivity analysis. We use the model to re-analyze an old NMDA-TTX oscillation model, and suggest an explanation of why it failed to reproduce the new experimental data that we present here.
|
|
| 10. |
- Huss, Mikael, 1974-
(författare)
-
Computational modeling of the lamprey CPG : from subcellular to network level
- 2007
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Due to the staggering complexity of the nervous system, computer modelling is becoming one of the standard tools in the neuroscientist's toolkit. In this thesis, I use computer models on different levels of abstraction to compare hypotheses and seek un- derstanding about pattern-generating circuits (central pattern generators, or CPGs) in the lamprey spinal cord. The lamprey, an ancient and primitive animal, has long been used as a model system for understanding vertebrate locomotion. By examining the lamprey spinal locomotor network, which is a comparatively simple prototype of pattern-generating networks used in higher animals, it is possible to obtain insights about the design principles behind the spinal generation of locomotion. A detailed computational model of a generic spinal neuron within the lamprey locomotor CPG network is presented. This model is based, as far as possible, on published experimental data, and is used as a building block for simulations of the whole CPG network as well as subnetworks. The model construction process itself revealed a number of interesting questions and predictions which point toward new laboratory experiments. For example, a novel potential role for KNaF channels was proposed, and estimates of relative soma/dendritic conductance densities for KCaN and KNaS channels were given. Apparent inconsistencies in predicted spike widths for intact vs. dissociated neurons were also found. In this way, the new model can be of benefit by providing an easy way to check the current conceptual understanding of lamprey spinal neurons. Network simulations using this new neuron model were then used to address aspects of the overall coordination of pattern generation in the whole lamprey spinal cord CPG as well as rhythm-generation in smaller hemisegmental networks. The large-scale simulations of the whole spinal CPG yielded several insights: (1) that the direction of swimming can be determined from only the very rostral part of the cord, (2) that reciprocal inhibition, in addition to its well-known role of producing alternating left-right activity, facilitates and stabilizes the dynamical control of the swimming pattern, and (3) that variability in single-neuron properties may be crucial for accurate motor coordination in local circuits. We used results from simulations of smaller excitatory networks to propose plausible mechanisms for obtaining self-sustaining bursting activity as observed in lamprey hemicord preparations. A more abstract hemisegmental network model, based on Izhikevich neurons, was used to study the sufficient conditions for obtaining bistability between a slower, graded activity state and a faster, non-graded activity state in a recurrent excitatory network. We concluded that the inclusion of synaptic dynamics was a sufficient condition for the appearance of such bistability. Questions about rhythmic activity intrinsic to single spinal neurons – NMDA-TTX oscillations – were addressed in a combined experimental and computational study. We showed that these oscillations have a frequency which grows with the concentration of bath-applied NMDA, and constructed a new simplified computational model that was able to reproduce this as well as other experimental results. A combined biochemical and electrophysiological model was constructed to examine the generation of IP3-mediated calcium oscillations in the cytosol of lamprey spinal neurons. Important aspects of these oscillations were captured by the combined model, which also makes it possible to probe the interplay between intracellular biochemical pathways and the electrical activity of neurons. To summarize, this thesis shows that computational modelling of neural circuits on different levels of abstraction can be used to identify fruitful areas for further experimental research, generate experimentally testable predictions, or to give insights into possible design principles of systems that are currently hard to perform experiments on.
|
|
