Hydrodynamic Forces on Macromolecules Protruding from Lipid Bilayers Due to External Liquid Flows.

It has previously been observed that an externally applied hydrodynamic shear flow above a fluid lipid bilayer can change the local concentration of macromolecules that are associated with the lipid bilayer. The external liquid flow results in a hydrodynamic force on molecules protruding from the lipid bilayer, causing them to move in the direction of the flow. However, there has been no quantitative study about the magnitude of these forces. We here use finite element simulations to investigate how the magnitude of the external hydrodynamic forces varies with the size and shape of the studied macromolecule. The simulations show that the hydrodynamic force is proportional to the effective hydrodynamic area of the studied molecule, Ahydro, multiplied by the mean hydrodynamic shear stress acting on the membrane surface, σhydro. The parameter Ahydro depends on the size and shape of the studied macromolecule above the lipid bilayer and scales with the cross-sectional area of the molecule. We also investigate how hydrodynamic shielding from other surrounding macromolecules decreases Ahydro when the surface coverage of the shielding macromolecules increases. Experiments where the protein streptavidin is anchored to a supported lipid bilayer on the floor of a microfluidic channel were finally performed at three different surface concentrations, Φ = 1%, 6%, and 10%, where the protein is being moved relative to the lipid bilayer by a liquid flow through the channel. From photobleaching measurements of fluorescently labeled streptavidin we found the experimental drift data to be within good accuracy of the simulated results, less than 12% difference, indicating the validity of the results obtained from the simulations. In addition to giving a deeper insight into how a liquid flow can affect membrane-associated molecules in a lipid bilayer, we also see an interesting potential of using hydrodynamic flow experiments together with the obtained results to study the size and the intermolecular forces between macromolecules in membranes and lipid bilayers

Aspects on optimisation of High Dose Methotrexate treatment in children with Acute Lymphoblastic Leukaemia

Childhood Acute Lymphoblastic Leukaemia (ALL) has a unique place in the history of oncology, as it was the first cancer to be cured by drugs. It is therefore an important model upon which concepts of chemotherapy in other malignancies have been developed. Methotrexate is a major component of most contemporary childhood ALL treatment protocols. The main objectives of this thesis were to investigate how methotrexate concentration time data from high dose methotrexate intravenous infusions relate to renal toxicity, to investigate how methotrexate concentrations in the cerebrospinal fluid are related to systemic levels and risk of a central nervous system (CNS) relapse, to build a population pharmacokinetic model from methotrexate concentration time data and assess how pharmacokinetic parameter predict relapse risk. An increase in serum creatinine of more than 50% could identify individuals with a delayed elimination of methotrexate whereas markers of tubular function were not related to a delayed elimination of methotrexate. A relationship between cerebrospinal fluid (CSF) and systemic concentrations was described with statistics that handle both the inter- and intra patient variability. Applying this relationship to a larger population suggests that increased CSF methotrexate concentrations are related to a decreased risk of a CNS relapse. Using a population pharmacokinetic model body weight was found to give a better model fit to the data than body surface area. Thus, a dose calculated from body weight may result in more predictable methotrexate concentrations. Patients with an increased clearance and volume of distribution had an increased risk of relapse. Pharmacokinetic parameters adjusted for body weight were, however, not significantly correlated to relapse risk. This further indicates that body weight is a preferred anthropomorphic measurement for dose modification of high dose methotrexate intravenous infusions in childhood ALL. The clinical value of these findings should be evaluated in prospective, controlled clinical trials before they are put into clinical practice

Förändringsarbete i försörjningskedjor - En studie på Findus Sverige

Att ha ett strukturerat arbetssätt för förändringsprocesser är viktigt för dagens försörjningskedjor, då dagens företag arbetar med flera och komplexa försörjningskedjor som ständigt är föremål för såväl stora som små förändringar. För att lyckas med en förändring i en organisation som ständigt är i rörelse, är det viktigt att ha en tydlig ledning av förändringen. Detta krav kommer att ställas på framtida ledare inom Supply Chain. Findus Sverige AB är idag en av Europas största aktörer på marknaden för frysta livmedel och arbetar med aktörer över hela världen. Företaget har väl utvecklade försörjningskedjor som ständigt förändras. De närmaste åren ska en stor förändring genomföras då ett nytt fryslager skall byggas vid fabriken i Bjuv. Den övergripande målsättningen med detta examensarbete är att skapa strukturerat sätt att arbeta med förändringar inom Findus Sverige AB. Studien är uppbyggd i tre delar: processkartläggning, datainsamling och skapande av nytt arbetssätt för förändring. Praktiskt kan rapporten användas för att skapa förståelse för vad som kan skapa problem vid förändringsarbete och hur dessa problem kan undvikas genom ett stukturerat arbetssätt. Rapporten utmynnar i en modell som ska ligga till grund för det framtida förändringsarbetet på Findus Sverige AB. Denna grund kan även appliceras på andra organisationer. Den kan i tillämpliga delar användas som grund för förändringsarbete även i andra organisationer

Inviwo -- A Visualization System with Usage Abstraction Levels

The complexity of today's visualization applications demands specific visualization systems tailored for the development of these applications. Frequently, such systems utilize levels of abstraction to improve the application development process, for instance by providing a data flow network editor. Unfortunately, these abstractions result in several issues, which need to be circumvented through an abstraction-centered system design. Often, a high level of abstraction hides low level details, which makes it difficult to directly access the underlying computing platform, which would be important to achieve an optimal performance. Therefore, we propose a layer structure developed for modern and sustainable visualization systems allowing developers to interact with all contained abstraction levels. We refer to this interaction capabilities as usage abstraction levels, since we target application developers with various levels of experience. We formulate the requirements for such a system, derive the desired architecture, and present how the concepts have been exemplary realized within the Inviwo visualization system. Furthermore, we address several specific challenges that arise during the realization of such a layered architecture, such as communication between different computing platforms, performance centered encapsulation, as well as layer-independent development by supporting cross layer documentation and debugging capabilities

Suppression-induced forgetting diminishes following a delay of either sleep or wake

We investigated the duration of suppression-induced forgetting (SIF), and the extent to which retrieval suppression differs between negative and neutral memories. We further examined if SIF was differently affected by sleep versus wake during the delay interval between retrieval suppression and re-test. Fifty participants first learned to associate neutral words with either neutral or negative images. Then, a subset of the words was shown again, and participants were asked to either recall (Think), or to suppress retrieval of (No-Think) the associated images. Finally, a memory test for all items was performed either immediately after the Think/No-Think (T/NT) phase (No Delay), or after a 3.5 h delay interval containing either sleep or wake. Results revealed a SIF effect only in the No Delay group, indicating that this forgetting effect dissipates already after a 3.5 h delay interval. Negative items were experienced as more intrusive than neutral ones during the T/NT phase

Auxin transport model for leaf venation.

The plant hormone auxin controls many aspects of the development of plants. One striking dynamical feature is the self-organization of leaf venation patterns which is driven by high levels of auxin within vein cells. The auxin transport is mediated by specialized membrane-localized proteins. Many venation models have been based on polarly localized efflux-mediator proteins of the PIN family. Here, we investigate a modelling framework for auxin transport with a positive feedback between auxin fluxes and transport capacities that are not necessarily polar, i.e. directional across a cell wall. Our approach is derived from a discrete graph-based model for biological transportation networks, where cells are represented by graph nodes and intercellular membranes by edges. The edges are not a priori oriented and the direction of auxin flow is determined by its concentration gradient along the edge. We prove global existence of solutions to the model and the validity of Murray's Law for its steady states. Moreover, we demonstrate with numerical simulations that the model is able connect an auxin source-sink pair with a mid-vein and that it can also produce branching vein patterns. A significant innovative aspect of our approach is that it allows the passage to a formal macroscopic limit which can be extended to include network growth. We perform mathematical analysis of the macroscopic formulation, showing the global existence of weak solutions for an appropriate parameter range.HJ is supported by the Gatsby Charitable Foundation (grant GAT3395-PR4). LMK is supported by the EPSRC grant EP/L016516/1 and the German National Academic Foundation

Interference cancellation detectors in a hardware implementation perspective

To combat interference between users in a DS/CDMA system, several multiuser detection schemes have been proposed. This paper presents a prestudy for a custom DSP implementation of a multi-user detector scheme based on non-decision directed interference cancellation. Two architectural implementation methods for asynchronous detection are suggested and mutually compared. Each of the architectures is shown to have its particular advantages and therefore, a design combining the methods described in this paper is worth future studies

Bcl11b mutations identified in murine lymphomas increase the proliferation rate of hematopoietic progenitor cells

<p>Abstract</p> <p>Background</p> <p>The telomeric region of mouse chromosome 12 has previously shown frequent allelic loss in murine lymphoma. The <it>Bcl11b </it>gene has been identified and suggested as a candidate tumor suppressor gene within this region. In this study, we aimed to elucidate whether <it>Bcl11b </it>is mutated in lymphomas with allelic loss, and whether the mutations we detected conferred any effect on cell proliferation and apoptosis.</p> <p>Methods</p> <p>Mouse lymphomas induced by 1,3-butadiene or 2',3'-dideoxycytidine were analysed for mutations in the <it>Bcl11b </it>gene using single strand conformation analysis and direct DNA sequencing. Effects on cell proliferation by the detected mutations were studied by expressing wild-type and mutant Bcl11b in the cytokine-dependent hematopoietic progenitor cell line FDC-P1, lacking endogenous Bcl11b expression.</p> <p>Results</p> <p>Missense and frameshift (FS) mutations were identified in 7 of 47 tumors (15%). Interestingly, all mutations were found between amino acids 778–844 which encode the three C-terminal DNA-binding zinc fingers. In FDC-P1 cells, wild-type Bcl11b suppressed cell proliferation, whereas the mutated versions (S778N, K828T, Y844C and FS823) enhanced proliferation several-fold.</p> <p>Conclusion</p> <p>The genetic alterations detected in this study suggest that the three C-terminal zinc fingers of Bcl11b are important for the DNA-binding. Cell proliferation was suppressed by overexpression of wild-type Bcl11b but enhanced by mutant Bcl11b, indicating that these mutations may be an important contributing factor to lymphomagenesis in a subset of tumors.</p

To what extent does smoking affect gingival bleeding response to supragingival plaque? Site‐specific analyses in a population‐based study

Background and objective - The aim of this study was to investigate the influence of smoking on the site‐specific association between bleeding on gingival probing and supragingival plaque and to assess whether this differs in different regions of the dentition. Methods - Data from a representative sample of 1911 adults (20‐79 years old) in Northern Norway were analyzed. Periodontal examinations consisted of full‐mouth recordings of periodontal probing depth (PD), bleeding on probing (BOP), and presence of supragingival plaque. Smoking status and background characteristics were self‐reported by questionnaire. The association between plaque and BOP was assessed in several three‐level (subject, tooth, and site) random intercept logistic regression models adjusted for PD, smoking status, socioeconomic factors, and body mass index. In a further model, it was assessed whether the association between supragingival plaque and BOP differed in different parts of the dentition. Results - For plaque‐free sites, bleeding tendency was lower in smokers, the odds ratio (OR) was 0.773 with a 95% confidence interval of 0.678‐0.881 as compared to non‐smokers (OR: 1; ref., P 2(4)= 32.043, P Conclusions - Smoking considerably attenuates the site‐specific association between plaque and BOP with a dose‐dependent effect. The effect of smoking did not differ across tooth types