Gradient echo-based quantitative MRI of human brain at 7T : Mapping of T1, MT saturation and local flip angle

Quantitative MRI (qMRI) refers to the process of deriving maps of MR contrast parameters, such as relaxation times, from conventional images. If the qMRI maps have a high degree of precision and a low degree of bias, they can be compared longitudinally, across subjects, and (ideally) between measurement protocols and research sites. They also provide a more direct biophysical interpretation of the pixel intensities. The increased magnetization of spins at ultra-high field (UHF) strengths of 7T and above could potentially be translated into higher spatial resolution and/or reduced scan time. This thesis tackles UHF-related challenges in qMRI, namely the increased inhomogeneity of the radio frequency (RF) field (B1) and increased specific absorption rate (SAR). The changing relaxation times (i.e. prolonged T1 and shortened T2) also needs to be accounted for.Here, spoiled gradient-recalled echo (GRE) techniques are employed to map (primarily) two structural MR parameters, i.e. the longitudinal relaxation time (T1) and the magnetization transfer (MT) saturation (MTsat). Because of its influence at UHF, emphasis is also put on mapping of the local flip angle. Primarily, qMRI is performed by the inversion of analytical signal equations, as opposed to numerical approaches.The process of implementing and modifying the dual flip angle (DFA) technique in conjunction with an MT-weighted GRE for 7T is described. Implementation is performed within the well-established multi-parameter mapping (MPM) framework and special attention is afforded to the reduction of biases as well as overcoming saftey restrictions imposed by SAR. An approach to obtain high-SNR low-bias flip angle maps at 7T, using the dual refocusing echo acquisition mode (DREAM) technique is also presented. This is important since high fidelity flip angle maps are a prerequisite in DFA-based T1-mapping and recommended for correcting MTsat at UHF. Furthermore, MPRAGE-based techniques are discussed. Firstly, it is demonstrated how to most effectively obtain B1-corrected MPRAGE images of “pure” T1 contrast using a sequential protocol This is followed by a description of T1-mapping using MP2RAGE. Finally, an innovative technique for simultaneous mapping of T1 and the local flip angle is introduced, dubbed “MP3RAGE”

Cultural and socio-political development in south Etruria. : The Biedano region in the 5th to 1st centuries BC

The town of Blera is situated in the southern parts of Etruria and has a history spanning more than 2,500 years. Its location between the two important Etruscan cities of Tarquinii and Caere has meant that Blera, for the entire Etruscan period (c. 750–50 BC), alternatively has found itself in either city’s sphere of interest. When Rome begins her expansion into Etruria, following the fall of the south Etruscan city of Veii in 396 BC, Blera is to be found in a conflict area between Tarquinii and Rome. The view of the Romanisation of Italy has shifted since the imperialistic interpretations of the early 20th century. According to this view, Roman culture and the Latin language were imposed on the native populations, considered part of an inevitable process. However, later scholarship has begun to question and challenge this view, developing alternative models for how to interpret the development. Rather than treating the Roman expansion on imperialistic grounds, it should be seen as a very complex political and social game, which in the end brought about the political unification of the Apennine peninsula under Rome. The driving mechanisms behind the development were the ambitions of Italy’s élite families. Their primary focus was to create and preserve power, influence, wealth and prestige for their own lineage. Their cities of origin, with belonging territories, became the tools with which they could achieve this. The consequence of this power struggle was that the city-states on the peninsula united in a federation, led by Rome. However, the creation of this new federal state did not immediately substitute the earlier local identities and cultures; the élite families of Etruria did not consider themselves “Roman”, because of their new alliances with Rome, but they could foresee that if they wanted to remain important and influential, Rome was the horse to bet on. The purpose of this thesis is to explore the cultural and socio-political development in the region where we find Blera when Rome and Tarquinii sought to expand their political influence. The main material groups studied for this thesis consist of the settlement types uncovered in earlier field surveys, tombs and necropoleis, the road network, epigraphic material, and the works of ancient authors

Marknadsmissbruksförordningen - Förhållandet till sanktionsavgifter och yttrandefriheten

Uppsatsen behandlar i två delar de nya reglerna om marknadsmanipulation och investeringsrekommendationer i Europeiska unionens förordning 596/2014 och svenska utredningen SOU 2014:46. Den ena delen behandlar bestämmelserna i förhållande till yttrandefriheten som den stadgas i yttrandefrihetsgrundlagen, regeringsformen och Europakonventionen. Den andra delen behandlar bestämmelserna i förhållande till Europakonventionen artikel 6, ifråga om huruvida de ska anses utgöra en anklagelse om brott eller ligga utanför definitionen. Det hela görs med utgångspunkt i två vanliga typer av inlägg om aktier på internet; rekommendationer i skrift samt podcasts med innehåll om aktier.This essay deals with the two parts of the new rules on market abuse and investment recommendations in EU Regulation 596/2014 and SOU 2014:46. The first part deals with the provisions in relation to the publication and freedom of expression as stipulated in the fundamental Law, the constitution and the ECHR. The second part deals with the provisions in relation to article 6 ECHR, as to whether they should be considered as a criminal charge or to be outside the definition. It’s all made on the basis of two common types of posts about stocks on the Internet; recommendations in writing as well as podcasts with content about stocks

Erkännandet av stater politik eller juridik? Erkännande teorier och dess effekter

This essay will debate the topic of state recognition in public international law. The purpose of the essay is to explore state recognition and determine the legal effects of recognition. The following questions aim to pinpoint the purpose of this essay: which state recognition theories exist and how does one differ from the other? And what legal effects does recognition have? Before discussing state recognition it is essential to examine what a state actually is. The common ground is generally found in the Montevideo Convention on Rights and Duties of States, where the basic requirements for an entity to achieve statehood is defined. The requirements consist of the following four criteria: a permanent population; a defined territory; government and a capacity to enter into relations with other states. If an entity fulfil these prerequisites the question arises what impact recognition has on an entity’s statehood? The two primary theories in state recognition are the constitutive theory and the declaratory theory. The constitutive theory emphasise the view that a state exist only when recognized by other states, and before recognition the state is solely an entity. The declaratory theory has a different point of view, this theory suggests that recognition only is a confirmation on the statehood of a state. And thus the entity already before the recognition exist as a sate, but with the recognition confirmation of statehood is given. Neither of these two theories have been able to extinguish the other, and there is no unanimous practice in public international law. Maybe this diversity in state recognition depends on the political part of recognition, and the fact that states are the legislative power and at the same time should be the law abiding citizens in public international law, thus having a foot in both camps. This makes the line of illegal acts and developing public international law somewhat hazy. The effects of recognition does not necessarily have to be limited to a certain effect, a state recognition may be declaratory in some cases and constitutive in other. This is noted in collective-recognitions by admission of an entity as a new member of the UN and collective non-recognitions for instance from the UN. The conclusion is that recognition may have declaratory and constitutive effects, and the reason for both these theories survival are that both are needed in today’s public international law to create stability in the international community.Uppsatsen behandlar ämnet erkännandet av stater, vilket är en folkrättslig disciplin. Syftet med uppsatsen är att försöka avgöra om erkännandet är deklaratoriskt eller konstitutivt, samt se vilka juridiska effekter ett erkännande har. Syftet genomförs med följande frågeställningar: vilka erkännande teorier existerar och hur skiljer sig de sig åt? Samt utröna vilka juridiska effekter ett erkännande har. För att kunna diskutera erkännandet av stater behövs en översiktlig redogörelse för vad som faktiskt är en stat. Den gängse meningen brukar vara att Montevideokonventionen från 1933 innehåller de kriterier som är grundläggande för att en entitet ska kunna utgöra en stat. Konventionens första artikel uppställer fyra stycken grundläggande kriterier: kravet på en permanent befolkning, ett styre, ett definierat territorium och en förmåga att ingå och upprätthålla mellanstatliga relationer. Uppfyller en entitet dessa kriterier övergår sedan frågan vilken betydelse ett erkännande har för en entitet status som stat. De två primära teorierna om erkännande är den deklaratoriska teorin och den konstitutiva teorin. Den konstitutiva teorin menar att en stat blir en stat i och med själva erkännandet från en annan stat inte innan. Den deklaratoriska teorin går till skillnad från den konstitutiva ut på att ett erkännande endast har bekräftande effekt, det vill säga entiteten är redan en stat men det blir nu bekräftat av en stat. Inte någon av de två teorierna är dominant inom folkrätten, möjligen bottnar det i att staterna är inkonsekventa i sina erkännanden, vilka till viss del är politiska. Staterna skapar de lagar de själva ska leva under, och gränsen mellan en orätt och en utveckling av folkrätten är väldigt diffus då staterna sitter på dubbla stolar. Och effekten av erkännandet behöver inte begränsas av teorierna till en bestämd effekt, ett erkännande kan ha konstitutiva effekter i vissa fall och deklaratoriska i ett annat. Vilket noteras vid kollektiva erkännanden genom inval i FN, och icke-erkännanden från exempelvis FN. Slutsatsen blir att ett erkännande kan både ha konstitutiva och deklaratoriska effekter och anledningen till att inte någon av erkännande teorierna har slagit ut den andra är då båda behövs i dagens folkrätt för att skapa ett stabilt internationellt plan

Bias field correction of MPRAGE by an external reference - The poor man's MP2RAGE

Purpose: To implement and evaluate a sequential approach to obtain semi-quantitative T1-weighted MPRAGE images, unbiased by B1 inhomogeneities at 7T.Methods: In the reference gradient echo used for normalization of the MPRAGE image, flipangle (αGE) and acquisition voxel size (Vref) was varied to optimize tissue contrast and acquisition time (Tacq). The finalized protocol was implemented at three different resolutions and the reproducibility was evaluated. Maps of T1 were derived based on the normalized MPRAGE through forward signal modelling.Results: A good compromise between tissue contrast and SNR was reached at αGE=3°. Areduction of the reference GE Tacq by a factor of 4, at the cost of negligible bias, was obtained by increasing Vref with a factor of 8 relative the MPRAGE resolution. The coefficient-ofvariation in segmented WM was 9±5% after normalization, compared to 24±12% before. The T1 maps showed no obvious bias and had reasonable values with regard to literature, especially after optional B1 correction through separate flip angle mapping.Conclusion: A non-interleaved acquisition for normalization of MPRAGE offers a simplealternative to MP2RAGE to obtain semi-quantitative purely T1-weighted images. Theseimages can be converted to T1 maps analogously to the established MP2RAGE approach. Scan time can be reduced by increasing Vref which has a miniscule effect on image quality

Radiofrequency bias correction of magnetization prepared rapid gradient echo MRI at 7.0 Tesla using an external reference in a sequential protocol

At field strengths of 7 T and above, T1-weighted imaging of human brain suffers increasingly from radiofrequency (RF) B1 inhomogeneities. The well-known MP2RAGE (magnetization prepared two rapid acquisition gradient echoes) sequence provides a solution but may not be readily available for all MR systems. Here, we describe the implementation and evaluation of a sequential protocol to obtain normalized magnetization prepared rapid gradient echo (MPRAGE) images at 0.7,0.8, or 0.9-mm isotropic spatial resolution. Optimization focused on the reference gradient-recalled echo (GRE) that was used for normalization of the MPRAGE. A good compromise between white-gray matter contrast and the signal-to-noise ratio (SNR) was reached at a flip angle of 3° and total scan time was reduced by increasing the reference voxel size by a factor of 8 relative to the MPRAGE resolution. The average intra-subject coefficient-of-variation (CV) in segmented white matter (WM) was 7.9 ±3.3% after normalization, compared to 20 ±8.4% before. The corresponding inter-subject average CV in WM as 7.6 ±7.6% and 13 ±7.8%. Maps of T1 derived from forward signal modelling showed no obvious bias after correction by a separately acquired flip angle map. To conclude, a non-interleaved acquisition for normalization of MPRAGE offers a simple alternative to MP2RAGE to obtain semi-quantitative purely T1-weighted images. These images can be converted to T1 maps, analogously to the established MP2RAGE approach. Scan time can be reduced by increasing the reference voxel size which has only a miniscule effect on image quality

Glucuronoyl Esterase Screening and Characterization Assays Utilizing Commercially Available Benzyl Glucuronic Acid Ester

Research on glucuronoyl esterases (GEs) has been hampered by the lack of enzyme assays based on easily obtainable substrates. While benzyl d-glucuronic acid ester (BnGlcA) is a commercially available substrate that can be used for GE assays, several considerations regarding substrate instability, limited solubility and low apparent affinities should be made. In this work we discuss the factors that are important when using BnGlcA for assaying GE activity and show how these can be applied when designing BnGlcA-based GE assays for different applications: a thin-layer chromatography assay for qualitative activity detection, a coupled-enzyme spectrophotometric assay that can be used for high-throughput screening or general activity determinations and a HPLC-based detection method allowing kinetic determinations. The three-level experimental procedure not merely facilitates routine, fast and simple biochemical characterizations but it can also give rise to the discovery of different GEs through an extensive screening of heterologous Genomic and Metagenomic expression libraries

Optimering över finita diskreta mått

Artificiell intelligens och neurala nätverk är just nu ett mycket omdebatterat ämne. I denna rapport undersöks metoder för optimering av mått, vilka kan användas i implementationen av bayesianska neurala nätverk. Dessa nätverk kan potentiellt förhindra överanpassning till träningsdata, och möjliggör kvantifiering av osäkerheten för utdata. Med hjälp av Python och PyTorch har tre modeller designade för bayesiansk regression implementerats: optimering över diskreta mått, polynomisk modell och linjärkombination av normalfördelade stokastiska variabler. Dessa har distinkta tillvägagångsätt att modellera data. I synnerhet undersöks hur effektivt och exakt de kan anpassas till given data. Linjärkombination av stokastiska variabler beskriver ett mått som en summa av stokastiska variabler multiplicerat med en godtycklig funktion. Genom att anta att stokastiska variablerna är normalfördelade kan stora förenklingar göras vilket gör algoritmen relativt okomplicerad. Vid testning påvisar denna metod god förmåga att modellera data med hög precision, men konvergerar långsammast. Det polynomiska neurala nätverket efterliknar linjärkombinationen vid fallet att funktionerna är termer i ett polynom. Lösningsgången är dock annorlunda då ett neuralt nätverk används och att stokastiska variablernas parametrar inte beräknas explicit. Istället matar nätverket ut en sammansatt funktion för medelvärde respektive standardavvikelse. Denna metod har något sämre precision men snabbare konvergenstid. Optimeringsalgoritmen över finita diskreta mått är tidigare outforskad i samband med neurala nätverk och automatisk differentiering. Här görs inga antagelser om måttets form utan det representeras helt av ett finit antal diskreta atomer. Atomernas massa justeras för att minimera en målfunktion men måttet bibehåller dess totala massa. Med denna metod kan valfri funktion beskrivas och stokastiska variablerna kan antas vara beroende eller oberoende. Testning tyder på att denna metod kräver fler datapunkter att träna på för att erhålla en acceptabel precision men är den snabbaste att konvergera av de tre. Olika målfunktioner undersöks, men det fastställs att log-likelihoodfunktionen är den bästa för stokastiska variabler. Denna används sedan för alla tester. Det kvarstår att undersöka metodernas effektivitet i större nätverk då denna rapport endast behandlar enklare problem med ett få antal parametrar. Slutsatsen är att vidare forskning för optimeringsalgoritmen över finita diskreta mått krävs innan metoden är tillämpbar i stora bayesianska neurala nätverk

Combining Substrate Specificity Analysis with Support Vector Classifiers Reveals Feruloyl Esterase as a Phylogenetically Informative Protein Group

Our understanding of how fungi evolved to develop a variety of ecological niches, is limited but of fundamental biological importance. Specifically, the evolution of enzymes affects how well species can adapt to new environmental conditions. Feruloyl esterases (FAEs) are enzymes able to hydrolyze the ester bonds linking ferulic acid to plant cell wall polysaccharides. The diversity of substrate specificities found in the FAE family shows that this family is old enough to have experienced the emergence and loss of many activities. In this study we evaluate the relative activity of FAEs against a variety of model substrates as a novel predictive tool for Ascomycota taxonomic classification. Our approach consists of two analytical steps; (1) an initial unsupervised analysis to cluster the FAEs substrate specificity data which were generated by cultivation of 34 Ascomycota strains and then an analysis of the produced enzyme cocktail against 10 substituted cinnamate and phenylalkanoate methyl esters, (2) a second, supervised analysis for training a predictor built on these substrate activities. By applying both linear and non-linear models we were able to correctly predict the taxonomic Class (∼86% correct classification), Order (∼88% correct classification) and Family (∼88% correct classification) that the 34 Ascomycota belong to, using the activity profiles of the FAEs. The good correlation with the FAEs substrate specificities that we have defined via our phylogenetic analysis not only suggests that FAEs are phylogenetically informative proteins but it is also a considerable step towards improved FAEs functional prediction.published_or_final_versio