Development of Robust and Standardized Cantilever Sensors Based on Biotin/Neutravidin Coupling for Antibody Detection

A cantilever-based protein biosensor has been developed providing a customizable multilayer platform for the detection of antibodies. It consists of a biotin-terminated PEG layer pre-functionalized on the gold-coated cantilever surface, onto which NeutrAvidin is adsorbed through biotin/NeutrAvidin specific binding. NeutrAvidin is used as a bridge layer between the biotin-coated surface and the biotinylated biomolecules, such as biotinylated bovine serum albumin (biotinylated BSA), forming a multilayer sensor for direct antibody capture. The cantilever biosensor has been successfully applied to the detection of mouse anti-BSA (m-IgG) and sheep anti-BSA(s-IgG) antibodies. As expected, the average differential surface stress signals of about 5.7 +/- 0.8 x 10(-3) N/m are very similar for BSA/m-IgG and BSA/s-IgG binding, i.e., they are independent of the origin of the antibody. A statistic evaluation of 112 response curves confirms that the multilayer protein cantilever biosensor shows high reproducibility. As a control test, a biotinylated maltose binding protein was used for detecting specificity of IgG, the result shows a signal of bBSA layer in response to antibody is 5.8 x 10(-3) N/m compared to bMBP. The pre-functionalized biotin/PEG cantilever surface is found to show a long shelf-life of at least 40 days and retains its responsivity of above 70% of the signal when stored in PBS buffer at 4 degrees C. The protein cantilever biosensor represents a rapid, label-free, sensitive and reliable detection technique for a real-time protein assay

Necessarily the old riddle necessary connections and the problem of induction

In this paper, I will discuss accounts to solve the problem of induction by introducing necessary connections. The basic idea is this: if we know that there are necessary connections between properties F and G such that F-ness necessarily brings about G-ness, then we are justified to infer that all, including future or unobserved, F s will be Gs. To solve the problem of induction with ontology has been proposed by David Armstrong and Brian Ellis. In this paper, I will argue that these attempts to solve the problem of induction fail. Necessary connections fail to reliably imply the respective regularities for two main reasons: Firstly, according to an argument originally presented by Helen Beebee, the respective necessary connections might be time-limited, and hence do not warrant inferences about future cases. As I will discuss, arguments against the possibility or explanatory power of time-limited necessary connections fail. Secondly, even time-unlimited necessary connections do not entail strict or non-strict regularities, and nor do they allow inferences about individual cases, which is an important function of inductive reasoning. Moreover, the proposed solution to the problem of induction would only apply to a tiny minority of inductive inferences. I argue that most inductive inferences are not easily reducible to the proposed inference pattern, as the vast majority of everyday inductive inferences do not involve necessary connections between fundamental physical properties or essences

Reorganisation of land holdings: Land development toolbox

Land reorganisation proceedings for re-regulation of the ownership-rights structure in rural areas are summarized under the term “reorganisation of land holdings” in Saxony. These have their legal basis in the Land Consolidation Act (FlurbG) or in section 8 of the Agricultural Adjustment Act (LwAnpG). Furthermore, land regulation can be conducted under the Building Code (BauGB). The goal is to develop capable, versatility structured agriculture and forestry, and to secure and improve rural areas as an attractive location for working, living, and recreation. Land management and land regulation serve “land development” and are thus in the area of tension of many different user interests

Comprehensive characterization of molecular interactions based on nanomechanics

Molecular interaction is a key concept in our understanding of the biological mechanisms of life. Two physical properties change when one molecular partner binds to another. Firstly, the masses combine and secondly, the structure of at least one binding partner is altered, mechanically transducing the binding into subsequent biological reactions. Here we present a nanomechanical micro-array technique for bio-medical research, which not only monitors the binding of effector molecules to their target but also the subsequent effect on a biological system in vitro. This label-free and real-time method directly and simultaneously tracks mass and nanomechanical changes at the sensor interface using micro-cantilever technology. To prove the concept we measured lipid vesicle (approximately 748*10(6) Da) adsorption on the sensor interface followed by subsequent binding of the bee venom peptide melittin (2840 Da) to the vesicles. The results show the high dynamic range of the instrument and that measuring the mass and structural changes simultaneously allow a comprehensive discussion of molecular interactions

Stora Torget in Uppsala : a study on use and experience

Diskussionen om den sociala aspekten av stadsplanering är ständigt aktuell. I stadskärnorna är parkerna och torgen viktiga offentliga ytor där människor kan mötas, men torgens funktion har varierat under historien. Vad fyller torgen egentligen för funktion idag? Jag har i min uppsats undersökt Stora torget i Uppsala. Det är en viktig knutpunkt i staden, med mycket mänsklig aktivitet och som står inför en trolig framtida förändring. Syftet med arbetet har varit att komma fram till hur ett centralt torg används och upplevs av människor. Stora torget undersöktes genom att utföra observationer och analyser på platsen. Resultaten visar att få människor uppehåller sig på torget och att de flesta mest passerar eller väntar på bussen. Aktiviteter på Stora torget är starkt kopplade till affärernas öppettider och vädret spelar stor roll för om människor uppehåller sig på torget. Sollägen, bra utblickar och att det går att stå eller sitta med ryggen skyddad påverkar vilka områden på torget som upplevs som behagliga och attraktiva. Busstrafiken är ett negativt inslag och hinder på Stora torget som orsakar buller och en känsla av otrygghet. Dock bidrar också busstrafiken till torgets funktion som mötesplats och ger ett flöde av människor till och från platsen vilket diskuteras i slutet av uppsatsen. Vidare diskuteras och stärks också resultatet med referenser till Jan Gehl och Kell Åström.The social aspect in urban planning is becoming more common and important in Sweden. Parks and squares in the city centers are important public places where people can meet, but the function of the squares have changed during the history. What function do the squares have today? I have in my thesis investigated Stora torget in Uppsala. It is an important node in the city, with a lot of human activity and it is facing a likely future change. The purpose of this thesis have been to determine how a central square is used and perceived by people. Stora torget was investigated by making observations and analysis. The results shows that few people are staying at the square and that most people just pass through or are waiting for the bus. Activities at Stora torget is highly linked to the stores opening hours and the weather also plays a major part in whether people are staying at the square or not. Sun aspects, good views and whether you can stay at the square with your back covered are factors that affect what areas of the square, that is perceived as pleasant and attractive. The bus traffic is a negative element and obstacle on Stora torget that cause noise and insecurity. However, the traffic also contribute to the square's function as a meeting point and provides a flow of people to and from the place, which is discussed in the end of the thesis. The result is also discussed and strengthened with references to Jan Gehl and Kell Åström

I tensed the laws and the laws won: non-eternalist humeanism

In this paper, I propose a variant of a Humean account of laws called "Open Future Humeanism" (OFH), which holds that since the laws supervene partly on future events, there are at any instant infinitely many possible future courses of events. I argue that if one wants to take the openness of the future that OFH proposes ontologically serious, then OFH is best represented within a growing block view of time. I further discuss some of OFH’s problems which stem from the fact that in this view, there are no laws as long as time progresses. These problems can be solved by adding a temporal operator to the laws, so that at any instant, we get a set of tensed laws which held up to and including that instant

The effects of diversity on creativity: A literature review and synthesis

In today's complex business world, the diversities within organizations, within teams, and of individual employees have emerged as a source of competitive advantage that can enhance creativity at multiple levels of analysis. However, the relationship between diversity and creativity at and across the individual, team, and organizational levels remains a topic of debate, despite ongoing scholarly interest. In this article, we address this debate by conducting a comprehensive multilevel review of 119 empirical studies that explores the effects of diversity on creativity. To structure this body of literature, we review studies based on their levels of analysis as well as the degrees of job-relatedness and the observability of diversity attributes they investigate. This approach helps to enable the discussion of the differential effects that numerous diversity attributes can have on creativity at the individual, team, and organizational levels, thus uncovering promising avenues for future research. Our multilevel perspective particularly points toward the heightened need for more cross-level and dynamic research designs and for extending conceptual ideas well known at one level of analysis to phenomena less understood at other levels of analysis. These approaches should improve the understanding of the complex, and therefore still puzzling, role of diversity for creativity

Molecular strategies to assess Botrytis cinerea in the context of viticulture and oenology

One of the most destructive pathogens in agriculture is the fungus Botrytis cinerea. It infects a wide range of crops, including grapes and vines. Due to its multiple and complex modes of attack, controlling the disease is a challenge in itself, but this is aggravated by growing concerns about traditional treatment strategies, climate change and the problematic predictability of infection sites. This work provides fundamental information on the laccase enzyme, a key component in overcoming plant defences, at the genomic level to understand potential differences in Botrytis cinerea strains based on regionality, vintage and laccase activity. To this end, eight strains were selected based on their origin, vintage and laccase activity and next generation sequencing was performed. The strains were then analysed using bioinformatic tools to assess differences in laccase genome regions. The study also investigated a classification method of Botrytis cinerea by molecular fingerprinting. Based on available microsatellite markers, 59 strains were analysed by SSR-PCR and the effectiveness of two methods, agarose gel electrophoresis and capillary sequencing, was compared. The aim of this aspect was to develop a simple method for strain differentiation and to evaluate potential markers for regionality, vintage and laccase activity. It also aimed to provide information on the general strain diversity in vineyards. The established strain differentiation method was used for a study on growth- and laccasemodulating properties of polyphenols. The last major part of this study was to optimise a qPCR method for the early detection of Botrytis cinerea on grapes, before it is visible to the eye. The detection method was adapted to reliably quantify biomass without cross-amplification of other pathogens relevant in vineyards, and the influence of different Botrytis cinerea strains on the quantification result was investigated. In addition to refining the method, the early detection limit was evaluated under laboratory conditions. The results of the bioinformatic evaluation of the genome indicate that different laccase gene regions are highly variable among each other and among different strains. While regional and evolutionary aspects seem to influence the genomic relationship, there was no clear correlation for laccase activity. There was also no clear correlation in the promoter and terminator regions of the genes. The results highlight the importance of gene expression studies, transcriptomics and proteomics, but also provide new targets for further research by analysing either highly conserved or evolutionarily changing laccase gene regions. This is particularly true for laccase gene regions that have not been the focus of previous experiments. The results for the molecular biology methods underline the diversity of Botrytis cinerea in vineyards. Strains from locally distant regions showed a similar level of differences as strains from locally closer regions. Although the complexity of Botrytis cinerea is high, it seems that general assumptions based on research on specific strains can be adapted to different regions, but it has to be considered that some strain characteristics can influence experimental results. Almost all strains could be assigned individual fingerprints with both methods implemented, although the capillary sequencer gave slightly better differentiation than agarose gel electrophoresis. However, the difference was marginal and agarose gel electrophoresis is much cheaper and can be performed by untrained personnel. The effectiveness for strain differentiation also became evident in the study of growth- and laccase- modulating properties, where a classification of strains for the research question was possible to discuss and interpret the obtained data. For the qPCR quantification and early detection method, the cross amplification of Cladosporium sp., Trichothecium roseum and especially Penicillium expansum could be excluded. There were some effects of the choice of strain on the quantification result. The detection of Botrytis cinerea in grapes under laboratory conditions was possible four days before it was visible to the naked eye. This component of the research signifies a substantial advancement in the implementation of this methodology in viticulture, enabling precises targeted treatments, thereby enhancing predictability while reducing the necessity for treatments. The findings offer invaluable insights into the Botrytis cinerea fungus, providing a foundation for research and agriculture concurrently. The results of the study have the potential to provide an important basis for the monitoring of the evolving strains of Botrytis cinerea in the context of climate change

Mammographic features and risk of breast cancer death among women with invasive screen-detected cancer in BreastScreen Norway 1996–2020

Objectives We explored associations between mammographic features and risk of breast cancer death among women with small ( Methods We included data from 17,614 women diagnosed with invasive breast cancer as a result of participation in BreastScreen Norway, 1996–2020. Data on mammographic features (mass, spiculated mass, architectural distortion, asymmetric density, density with calcification and calcification alone), tumour diameter and cause of death was obtained from the Cancer Registry of Norway. Cox regression was used to estimate hazard ratios (HR) with 95% confidence intervals (CI) for breast cancer death by mammographic features using spiculated mass as reference, adjusting for age, tumour diameter and lymph node status. All analyses were dichotomised by tumour diameter (small versus large). Results Mean age at diagnosis was 60.8 (standard deviation, SD=5.8) for 10,160 women with small tumours and 60.0 (SD=5.8) years for 7454 women with large tumours. The number of breast cancer deaths was 299 and 634, respectively. Mean time from diagnosis to death was 8.7 (SD=5.0) years for women with small tumours and 7.2 (4.6) years for women with large tumours. Using spiculated mass as reference, adjusted HR for breast cancer death among women with small tumours was 2.48 (95% CI 1.67–3.68) for calcification alone, while HR for women with large tumours was 1.30 (95% CI 1.02–1.66) for density with calcifcation. Conclusions Small screen-detected invasive cancers presenting as calcification and large screen-detected cancers presenting as density with calcifcation were associated with the highest risk of breast cancer death. Clinical relevance statement Small tumours (<15 mm) presented as calcification alone and large tumours (≥ 15 mm) presented as density with calcification were associated with the highest risk of breast cancer death among women with screen-detected invasive breast cancer diagnosed 1996–2020

Ett grönt mellanrum i Gottsunda

Arbetet syftar till att uppmärksamma de bostadsnära och naturlika mellanrummens upplevelsevärden genom att undersöka karaktären och kvaliteter hos ett grönt mellanrum i Gottsunda. Med idéförslag i form av tillägg visar arbetet på hur mellanrummets karaktär kan förstärkas. I takt med att storstäderna växer minskar grönytorna. Studier har visat att människor har behov av varierad grönska i städer för att må bra. Framförallt erbjuder naturen återhämtning, detta gäller även för den bostadsnära natur som finns i stadsmiljö. En typ av bostadsnära natur är de, ibland svårdefinierade och naturlika, grönområden som ofta finns insprängda i stadsstukturer. De kan beskrivas som gröna mellanrum som har blivit över eller sparats mellan stadsdelar eller kvarter. Förtätningen av städerna leder till att dessa typer av grönområden frekvent exploateras trots att de erbjuder lättillgänglig naturvistelse. Det krävs ofta att dessa områden är skyddade eller har höga ekologiska värden för att de ska sparas. Om ett område har höga upplevelsevärden är dock risken mindre att de bebyggs. Som framtida landskapsarkitekter besitter vi metoder och verktyg för att se, beskriva och analysera landskapet runt oss. Genom landskapsarkitektens expertis kan vi därför bidra med att lyfta upplevelsevärdet som ett viktigt ämne i diskussionen om de gröna mellanrummens framtid. Arbetet har inneburit flera platsstudier för att uppleva och få en förståelse för det gröna mellanrummet i Gottsunda och dess omgivningar. Genom att besöka området flera gånger, vid olika tidpunkter och med olika metoder har vi insett att mellanrummet är komplext och svårt att sammanfatta i en karaktär. Att skissa har varit vår främsta metod genom arbetet och ett verktyg för att kommunicera och dokumentera tankar, idéer och kunskaper om området. De många besöken och de olika metoderna gjorde att vi upplevde att de olika karaktärsdragen i området förändrades beroende på tidpunkt och väder. Därför valde vi att beskriva upplevelsen av området och dess karaktärsdrag ur fyra olika perspektiv; i ett större sammanhang, utifrån, inifrån och som något i förändring. Utifrån dessa fyra perspektiv gestaltade vi sedan fyra idéförslag. Tillsammans och var för sig förstärker idéförslagen olika karaktärer som vi har identifierat samt visar på ett omhändertagande av platsen. Att utgå från vår upplevelse, att se det unika med platsen, dess karaktär och att undersöka platsen med hjälp av skissandet som främsta verktyg har visat sig vara positivt för vår kreativitet och har gjort att vi har fått en djupare förståelse för platsen. Med detta arbete och våra idéförslag vill vi belysa de gröna mellanrummen och problematiken kring dess försvinnande i dagens stadsplanering. Vi vill också visa på vikten av att besöka en plats många gånger, att låta platsupplevelsen ta tid och att en plats karaktär kan tydliggöras på olika sätt, med olika medel och genom olika perspektiv.This thesis aims to highlight the experiential values of green spaces by investigating the character and qualities of a green space in Gottsunda. With designed additions this thesis shows how the character of the green space can be emphasized. In Sweden the green areas in the cities are decreasing as a result of the urbanisation. Studies have shown that people have a need of varied types av greenery in the cities for their well-being. Nature is restorative and this also applies to urban nature located close to our homes. One type of urban nature are the anonymous and nature-like green areas that has been leftover in the city structure. These type of green spaces are often exploited as a result of the densification of the cities even though they offer an easy access to nature. Laws of protection and high ecological values are often requirements for its preservation. High experiential values may reduce the risk of this type of green spaces to be exploited. As future landscape architects we have the methods to see, describe and analyse the landscapes around us. Therefore we can contribute by conveying the values of the green spaces as an important topic to the debate about the future of the green spaces. In this thesis we have done several site surveys to experience and to get knowledge of the green space in Gottsunda and its surroundings. By visiting the place several times and by using different methods, we realized that the green space is complex and hard to summarize into one character. Sketching was the main method throughout the whole process and a tool for communicating and documenting our thoughts, ideas and knowledge about the place. The different methods during the site surveys made us experience the place through different perspectives and made us experience a variety of characters, which also changed depending on time and weather. We therefore choose to describe the experience of the area and its characters from four different perspectives; in a larger context, from the outside, from within and as something in change. A design proposal was developed for each one of these perspectives. Together and by themselves they highlight and emphasize the different characters we have experienced and they all show signs of care of the green space. Starting from our experience of a place, seeing the uniqueness of the place, its character and exploring the place by sketching has proven to be positive for our creativity and have lead to a deeper understanding of the place. With this thesis we want to highlight the green spaces and their role in urban planning. We also want to inspire others to take the time to get to know a place by visiting a site many times. The character of a place can be emphasized in different ways, with different means and through different perspectives