Many-body effects in tracer particle diffusion with applications for single-protein dynamics on DNA

30% of the DNA in E. coli bacteria is covered by proteins. Such high degree of crowding affect the dynamics of generic biological processes (e.g. gene regulation, DNA repair, protein diffusion etc.) in ways that are not yet fully understood. In this paper, we theoretically address the diffusion constant of a tracer particle in a one dimensional system surrounded by impenetrable crowder particles. While the tracer particle always stays on the lattice, crowder particles may unbind to a surrounding bulk and rebind at another or the same location. In this scenario we determine how the long time diffusion constant ${\cal D}$ (after many unbinding events) depends on (i) the unbinding rate of crowder particles $k_{\rm off}$, and (ii) crowder particle line density $\rho$, from simulations (Gillespie algorithm) and analytical calculations. For small $k_{\rm off}$, we find ${\cal D}\sim k_{\rm off}/\rho^2$ when crowder particles are immobile on the line, and ${\cal D}\sim \sqrt{D k_{\rm off}}/\rho$ when they are diffusing; $D$ is the free particle diffusion constant. For large $k_{\rm off}$, we find agreement with mean-field results which do not depend on $k_{\rm off}$. From literature values of $k_{\rm off}$ and $D$, we show that the small $k_{\rm off}$-limit is relevant for in vivo protein diffusion on a crowded DNA. Our results applies to single-molecule tracking experiments.Comment: 10 pages, 8 figure

IFRS 8 - amerikansk standard i europeisk redovisning

Syftet med uppsatsen är att undersöka och analysera IASBs framgång och tillit som internationell standardsättare, då nya standarder utvecklas i samarbete med FASB. Undersökningen har genomförts utifrån en induktiv ansats. Metoden har gått ut på att analysera artiklar och comment letters, för att sedan knyta an denna empiri med vår teoretiska referensram. Det teoretiska perspektivet har i stor omfattning utgått ifrån att beskriva den institutionella teorin. Utifrån teorin undersöks vilka formella och i nformella regler, normer och värderingar som styr organisationen och den institutionella miljö där IASB verkar. I empirin framförs åsikter från comment letters, artiklar och dokument. I dessa återges olika åsikter om standarden IFRS 8 och ledningspespektivet. Användarna är den grupp som har lägst förtroende för IASB och är därmed de som är mest negativt inställda till IASB. Framställarna är generellt sett positiva till standarden och gentemot dessa har IASB en stark legitimitet för sitt agerande. IASB har starkt stöd från de flesta standardsättare och även ett flertal av instituten och regulatorerna. Genom IFRS 8 blir det amerikanska inflytandet över IASB tydligt, vilket innebär en balansgång för IASB, med FASB på ena sidan och sin trovärdighet på andra sidan

A multi-center study of their physicochemical characteristics, cell culture and in vivo experiments

PVP-capped silver nanoparticles with a diameter of the metallic core of 70 nm, a hydrodynamic diameter of 120 nm and a zeta potential of −20 mV were prepared and investigated with regard to their biological activity. This review summarizes the physicochemical properties (dissolution, protein adsorption, dispersability) of these nanoparticles and the cellular consequences of the exposure of a broad range of biological test systems to this defined type of silver nanoparticles. Silver nanoparticles dissolve in water in the presence of oxygen. In addition, in biological media (i.e., in the presence of proteins) the surface of silver nanoparticles is rapidly coated by a protein corona that influences their physicochemical and biological properties including cellular uptake. Silver nanoparticles are taken up by cell-type specific endocytosis pathways as demonstrated for hMSC, primary T-cells, primary monocytes, and astrocytes. A visualization of particles inside cells is possible by X-ray microscopy, fluorescence microscopy, and combined FIB/SEM analysis. By staining organelles, their localization inside the cell can be additionally determined. While primary brain astrocytes are shown to be fairly tolerant toward silver nanoparticles, silver nanoparticles induce the formation of DNA double-strand-breaks (DSB) and lead to chromosomal aberrations and sister-chromatid exchanges in Chinese hamster fibroblast cell lines (CHO9, K1, V79B). An exposure of rats to silver nanoparticles in vivo induced a moderate pulmonary toxicity, however, only at rather high concentrations. The same was found in precision-cut lung slices of rats in which silver nanoparticles remained mainly at the tissue surface. In a human 3D triple-cell culture model consisting of three cell types (alveolar epithelial cells, macrophages, and dendritic cells), adverse effects were also only found at high silver concentrations. The silver ions that are released from silver nanoparticles may be harmful to skin with disrupted barrier (e.g., wounds) and induce oxidative stress in skin cells (HaCaT). In conclusion, the data obtained on the effects of this well-defined type of silver nanoparticles on various biological systems clearly demonstrate that cell-type specific properties as well as experimental conditions determine the biocompatibility of and the cellular responses to an exposure with silver nanoparticles

A Monte Carlo study of the particle mobility in crowded nearly one-dimensional systems.

The study of crowding effects on particle diffusion is a large subject with implications in many scientific areas. The studies span from pure theoretical calculations to experiments actually measuring the movement of proteins diffusing in a cell. Even though the subject is important and has been studied heavily there are still aspects not fully understood.   This report describes a Monte Carlo simulation approach (Gillespie algorithm) to study the effects of crowding on particle diffusion in a quasi one-dimensional system. With quasi meaning that the particles diffuses on a one-dimensional lattice but has the possibility to disassociate from the lattice and then rebind at a latter stage. Different binding strategies are considered: rebinding to the same location and randomly choosing the binding location. The focus of the study is how these strategies affects the mobility (diffusion coefficient) of a tracer particle. The main result of this thesis is a graph showing the diffusion coefficient as a function of the binding rate for different binding strategies and particle densities. We provide analytical estimates for the diffusion coefficient in the unbinding rate limits which show good agreement with the simulations.Hur "trängsel" (från engelskans "crowding" t ex molecular crowding) påverkar diffusionsprocesser är viktigt inom många olika vetenskapliga områden. Forskningen som för tillfället utförs sträcker sig från rent teoretiska beräkningar till experiments där man kan följa enskilda proteiners rörelse i en cell. Även fast ämnet är viktig och väl undersökt finns det fortfarande många aspekter som man inte förstår till fullo. I det här examensarbetet beskrivs en Monte Carlo metod (Gillespie algoritmen) för att studera hur trängsel påverkar en partikel som diffunderar i ett "nästan" en-dimensonellt system. Det är nästan en-dimensionellt i det avsedde att partiklarna diffunderar på ett gitter men kan binda av från gittret och binda tillbaka i ett senare skedde. Olika metoder för hur partiklarna binder till gittret undersöks: Återbinding till avbindingsplatsen och slumpmässigt vald återbindingsplats. Fokus ligger på att förklara hur dessa påverkar mobiliteten (diffusionskonstanten) av en spårningspartikel (tracer particle). Resultatet är en graf som visar diffusionskonstanten för spårningspartikeln som en funktion av avbindingsfrekvens för olika bindingstrategier och partikeldensiteter. Vi ger också analytiska resultat i gränsvärdet för höga och låga avbindingstakter vilka stämmer bra överens med simuleringar

Interaktion von Silbernanopartikeln mit Human- und Schweinehaut

The rising number of antibiotic-resistant bacteria strains point to the need of new strategies dealing with this threat. One mayor outcome in modern biomedical engineering is the development of nano-sized silver particles (AgNP).With its high antibiotic potential AgNP became one of the fastest growing products in nanotechnology. The particles can be found, e.g., in coatings for all kinds of surgical instruments or implants, in textiles, room sprays, creams and in wound dressings. Regarding the prevention and treatment of bacterial infections the negative effect on mammalian cells cannot be ignored. This is way this dissertation will focus its current research on the matter. The present study addresses the penetration of 70 nm-sized AgNP into the skin, the impact on skin cell viability and the induction of free radicals (ROS). The penetration of these non-fluorescent particles was explored by means of Raman microscopy and fluorescence lifetime imaging microscopy on porcine skin and transmission electron microscopy (TEM) as well as scanning transmission X-ray microscopy (STXM) on human excised skin. The experiments showed no uptake of the AgNP into the viable epidermis in intact skin. In terms of injured skin (e.g., wounds or burned skin) AgNP penetrate into the living tissue and come in contact with the cells, which is shown by TEM and STXM, and are taken-up and stored by the skin cells (HaCaT). The incubation with silver led to morphological changes of the nuclei and the cell membranes, which indicates cell death. Furthermore it was demonstrated that the presence of AgNP led to a decreasing cell viability and the production of inflammatory cytokines, i.a. IL-1, IL-6 and IL-8. It was also shown by another method of AgNP-synthesis that the major impact to the cell viability is due to the presence of silver ions (Ag+). Particles produced and stored under air (with a high Ag+ ions content) were compared to those synthesized and stored under the inert gas argon (Ar) with a low Ag+ ions concentration. It was found that Ag+ ions released during particle storage are responsible for most of the AgNP related cytotoxic effects. This was underlined by the detection of intracellular ROS induced in HaCaT cells incubated with the two AgNP types. ROS formation was investigated by means of electron paramagnetic resonance (EPR) spectroscopy. These experiments explored the high ROS induction by AgNP under oxygen in contrary to the particles under Ar. These results were also confirmed by investigations on one part of the antioxidant system i.e. measurement of the intracellular glutathione. In conclusion, the present results indicate no dermal uptake of AgNP. In the specific cases of injured skin the AgNP interact with the living cells and cause toxic effects, which might lead to irritation and inflammation. This is associated with an increasing ROS production and therefore the damage on cellular membranes, DNA or proteins. The use of AgNP (Ar) avoid the presence of released Ag+ ions and allow exploiting the beneficial properties of NP i.e. slow and sustained release of Ag+ ions. These results highlight the complexity of silver toxicity in medical applications, which need to be thoroughly evaluated for safe use of these nanomaterials in dermatology and other fields.Nanopartikel (NP) spielen eine immer größere Rolle im täglichen Leben. Sie besitzen spezielle Eigenschaften, die auf ihren vergrößerten Oberflächen-zu-Volumen-Verhältnis beruhen und sind z.B. besonders reaktiv. In dieser Arbeit werden NP auf ihre Interaktion mit Haut und Hautzellen untersucht. Vor allem Silbernanopartikel (AgNP), die sich auf Grund ihrer antibakteriellen Eigenschaften steigendem Interesse erfreuen, sind hier in den Fokus gerückt. Speziell in Beschichtungen für OP-Bestecke oder Implantaten, in Textilien, Raumsprays oder Wunddressings sind sie ein fester Bestandteil. Die hohe antibakterielle Wirkung ist eindeutig vorhanden, jedoch können auch Beeinträchtigungen von eukaryotischen Zellen nicht ausgeschlossen werden. Diese Arbeit untersucht die Aufnahme von NP in die Haut, die Wechselwirkung mit Hautzellen und Induktion von oxidativem Stress. Die Untersuchung der Penetration von ungelabelten Partikeln ist kompliziert und wurde hier durch den Einsatz von Raman Mikroskopie, Fluoreszenzlebensdauer Mikroskopie, Röntgenmikroskopie und Elektronenmikroskopie an exzidierter Humanhaut und Schweinehaut realisiert. Solange eine intakte Hautbarriere vorhanden war, konnte keine Penetration in der lebenden Hautschichten beobachtet werden. Jedoch treten Schädigungen der Hautbarriere häufig auf (z.B. durch Wunden, Verbrennungen, Operationen), was wiederum die Penetration der NP ermöglicht. So kommt es zum Kontakt zwischen AgNP und Zellen. Diese Situationen wurden simuliert und die Aufnahme in die Zellen konnte nachgewiesen werden. Dies führte zu morphologischen Änderungen der Zelle, wie z.B. der Auflösung des Zellkerns. Die Toxizität der AgNP auf Keratinozyten wurde untersucht und dabei sowohl eine AgNP-abhängige Verringerung der Zellviabilität als auch die Ausschüttung von inflammatorischen Mediatoren detektiert. Durch eine spezielle Synthesemethoden wurde AgNP bereitgestellt, welche eine hohe als auch eine niedrige Anzahl von Silberionen (Ag+) aufwiesen. Es wurde gezeigt, dass die Ag+ Ionen größtenteils die Verantwortung für die Toxizität tragen. Diese Toxizität konnte mittels der Elektronenspinresonanz-Spektroskopie auf oxidativen Stress zurückgeführt werden. Durch die Ag+ Ionen werden zum einen Membranen beschädigt und somit Radikale induziert, zum anderen inhibieren diese Ionen das antioxidative System der Zellen, welches für die oxidative Balance sorgt. Daraus entwickelt sich ein Überschuss an freien Radikalen, welcher letztendlich zum Zelltod führt. Zusammenfassend dokumentiert diese Arbeit, dass die hier untersuchten NP eine intakte Hautbarriere nicht überwinden können. Hautschädigungen führen jedoch zu einem Durchbruch der NP und zur Interaktion mit Hautzellen. Infolge verschiedener Kaskaden und Reaktionen wird das oxidative Gleichgewicht der Zellen gestört was zum Zelltod führt. Diese Effekte treten bei AgNP, die unter Argon (Ar) synthetisiert wurden verringert auf. Die Ergebnisse dieser Arbeit belegt die Toxizität von AgNP aber auch mögliche Lösungen. Deshalb sollte die Forschung weitergeführt werden, um den Nutzen zu erhöhen und Risiken einzuschränken

Röjning för omställning från trakthyggesbruk till hyggesfritt skogsbruk – en fallstudie i Vätteskogen, Skinnskatteberg

För att anses hållbart ska modernt skogsbruk jämställa sociala, ekonomiska och biologiska värden. Svenskt skogsbruk har historiskt sett fokuserat på ett brukande med fokus på jämn och hög avverkningsnivå men idag går trenden mot ett mer mångsidigt brukande, även globalt. Tätortsnära skogar som kräver hänsyn till sociala värden är ett exempel på fall som förbisetts. Idag är många tätortsnära skogar i Sverige så kallade enskiktade trakthyggesbrukade skogar trots att sociala värden gynnas av hyggesfria metoder. Därav finns det ett behov att ställa om dessa trakthyggesbrukade skogar till skog som brukas hyggesfritt. Syftet med denna studie var att utvärdera tillvägagångssätt vid röjning för omföring från trakthyggesbruk till hyggesfritt skogsbruk. Ett delsyfte var att få utlåtande om resultatet av tillvägagångssätten från olika nyttjare av en tätortsnära skog. En fallstudie utfördes som fokuserar på omställning av en ungskogsavdelning i Vätteskogen, en tätortsnära skog i närheten av Skinnskatteberg, Västmanlands län från trakthyggesbruk till hyggesfritt skogsbruk genom röjning. Studien fokuserade på att utvärdera sex olika röjningsmetoder och deras lämplighet för hyggesfritt skogsbruk. Metoderna var: Mellanskiktsmetoden, Skiktat med flera trädslag, Kronobergsmetoden, Skiktat med färre trädslag, Toppröjningsmetoden samt Konventionell röjning. I förhållande till Konventionell röjning visade sig alla alternativa metoder öka variationen och höjdskiktningen genom ett högt antal stammar i de lägre höjdklasserna. Mellanskiktsmetoden tog minst tid i förhållande till prestationsnormen, näst minst tid tog Konventionell röjning. De två metoderna Skiktat med flera trädslag och Skiktat med färre trädslag tog cirka fyra gånger längre tid än prestationsnormen. En rundvandring där några av Vätteskogens intressenter fick betygsätta de olika metoderna resulterade i att metoden Skiktat med flera trädslag fick bäst betyg. Minst omtyckt var Toppröjningsmetoden och den oröjda referensytan. Slutsatserna ur studien är att de alternativa röjningsmetoderna visat större höjdvariation jämfört med Konventionell röjning samt att metoderna Skiktat med flera trädslag och Skiktat med färre trädslag uppskattades mest av intressenterna. Att statistiskt fastställa tidsåtgången för de alternativa röjningsmetoderna och följa de skogstillstånd som skapas av dem (skiktning samt behov av framtida skötsel) kvarstår.Modern forestry is supposed to consider both social, economic, and biological values to count as sustainable. Through history Swedish forestry has focused on even and high production levels but today winds have turned towards a more equal focus on all values, same thing globally. One example of cases that has been marginalized is recreational forests which host high social values. Many recreational forests in Sweden today are managed with rotation forestry (RF) though social values favors continuous cover forestry (CCF). Therefore, there is a demand for converting these forests to be managed with CCF methods. The objective of the study was to evaluate different ways of converting RF managed forests to CCF management by pre-commercial thinning (PCT). A part of the objective was to get an opinion from different users of a recreational forest. This study focuses on a case of converting a section of the forest “Vätteskogen” close to Skinnskatteberg, Västmanland county from RF to CCF. The forest section was mainly young forest, and the conversion work was done by PCT. The methods where: Conventional PCT, Mid-layer method, Layered with less tree species, Layered with several tree species, Top-PCT method and “Kronobergsmetoden”. All the alternative methods showed increased variation and layering with a high number of stems in the lower height classes compared to conventional PCT. The Mid-layer method took the least amount of time compared to the accomplishment norm for cleaning and close to that was the conventional PCT. The methods “Layered with several tree species” and “Layered with fewer tree species” both took around four times the accomplishment norm. A tour of the area where some of the stakeholders in “Vätteskogen” got to evaluate and grade the different methods resulted in that the “Layered with several tree species”-method got the highest score. The Top-PCT method and an un-thinned reference area got the lowest score. On the question of which method the respondents preferred they chose the “Layered with several tree species”- method. Conclusions of the study is that the alternative methods showed higher height variations compared to Conventional PCT. The methods Layered with fewer- and several tree species where the most popular among the respondents. To statistically secure how time consuming the alternative methods are and to follow the forest state that follow them remains

Magnetic and structural characterization of CoFeZr thin films grown by combinatorial sputtering

We report on a detailed investigation of structural and magnetic properties of thin CoFeZr films, produced by combinatorial cosputtering, with compositions in the ranges 30-85 at.% Co, 12-63 at.% Fe, and 4-8 at.% Zr. Extended x-ray absorption fine structure and x-ray diffraction measurements reveal that alloys with a Zr content below 5 at.% are polycrystalline with a bcc structure, while an amorphous morphology is stabilized at Zr contents above 6 at.%. All samples display a growth-induced in-plane uniaxial anisotropy, which is closely related to the Zr concentration gradients across the wafers. A model for the angular dependence of the reduced remanence, including a Gaussian distribution of easy/hard anisotropy axes, is presented and successfully used to fit the data for all samples. The magnetic moments of the polycrystalline films approximately follow the Slater-Pauling curve, and the magnetic moments of the amorphous films follow a similar trend, but with about 20 % lower values. X-ray magnetic circular dichroism measurements show, for the amorphous films, that the Co moments are virtually constant at 1.7(2)mu(B)/atom

Unveiling the local structure of the amorphous metal Fe(1−x)Zrx\text {Fe}_{(1-x)}\text {Zr}_x Fe ( 1 - x ) Zr x combining first-principles-based simulations and modelling of EXAFS spectra

Abstract Amorphous alloys exhibit useful properties such as the excellent soft magnetic behaviour of Fe-based metallic glasses. The detailed structure of amorphous $$\text {Fe}_{(1-x)}\text {Zr}_x$$ Fe ( 1 - x ) Zr x with x = 0.07, 0.10, and 0.20 is in this work explored through a synergetic combination of atomistic simulations and experimental characterisation. Thin-film samples were investigated using X-ray diffraction and extended X-ray absorption fine structure (EXAFS), while the corresponding atomic structures were simulated using an efficient first-principles-based method called stochastic quenching (SQ). The simulated local atomic arrangements are investigated by constructing the radial- and angular-distribution functions, as well as by Voronoi tesselation. The radial distribution functions are then used to construct a model to fit simultaneously the experimental EXAFS data of multiple samples with different compositions, creating a simple yet accurate description of the atomic structures valid for any composition in the range x = 0.07 to 0.20, using a minimal number of free parameters. This approach significantly improves the accuracy of the fitted parameters and allows us to relate the compositional dependence of the amorphous structures with the magnetic properties. The proposed EXAFS fitting process can be generalised to other amorphous systems, contributing to the understanding of structure-property relationships and the development of amorphous alloys with tailored functional properties