The objectives of this thesis are focused on research in machine learning for coreference resolution. Coreference resolution is a natural language processing task that consists of determining the expressions in a discourse that mention or refer to the same entity. The main contributions of this thesis are (i) a new approach to coreference resolution based on constraint satisfaction, using a hypergraph to represent the problem and solving it by relaxation labeling; and (ii) research towards improving coreference resolution performance using world knowledge extracted from Wikipedia. The developed approach is able to use entity-mention classi cation model with more expressiveness than the pair-based ones, and overcome the weaknesses of previous approaches in the state of the art such as linking contradictions, classi cations without context and lack of information evaluating pairs. Furthermore, the approach allows the incorporation of new information by adding constraints, and a research has been done in order to use world knowledge to improve performances. RelaxCor, the implementation of the approach, achieved results in the state of the art, and participated in international competitions: SemEval-2010 and CoNLL-2011. RelaxCor achieved second position in CoNLL-2011. / La resolució de correferències és una tasca de processament del llenguatge natural que consisteix en determinar les expressions d'un discurs que es refereixen a la mateixa entitat del mon real. La tasca té un efecte directe en la minería de textos així com en moltes tasques de llenguatge natural que requereixin interpretació del discurs com resumidors, responedors de preguntes o traducció automàtica. Resoldre les correferències és essencial si es vol poder “entendre” un text o un discurs. Els objectius d'aquesta tesi es centren en la recerca en resolució de correferències amb aprenentatge automàtic. Concretament, els objectius de la recerca es centren en els següents camps: + Models de classificació: Els models de classificació més comuns a l'estat de l'art estan basats en la classificació independent de parelles de mencions. Més recentment han aparegut models que classifiquen grups de mencions. Un dels objectius de la tesi és incorporar el model entity-mention a l'aproximació desenvolupada. + Representació del problema: Encara no hi ha una representació definitiva del problema. En aquesta tesi es presenta una representació en hypergraf. + Algorismes de resolució. Depenent de la representació del problema i del model de classificació, els algorismes de ressolució poden ser molt diversos. Un dels objectius d'aquesta tesi és trobar un algorisme de resolució capaç d'utilitzar els models de classificació en la representació d'hypergraf. + Representació del coneixement: Per poder administrar coneixement de diverses fonts, cal una representació simbòlica i expressiva d'aquest coneixement. En aquesta tesi es proposa l'ús de restriccions. + Incorporació de coneixement del mon: Algunes correferències no es poden resoldre només amb informació lingüística. Sovint cal sentit comú i coneixement del mon per poder resoldre coreferències. En aquesta tesi es proposa un mètode per extreure coneixement del mon de Wikipedia i incorporar-lo al sistem de resolució. Les contribucions principals d'aquesta tesi son (i) una nova aproximació al problema de resolució de correferències basada en satisfacció de restriccions, fent servir un hypergraf per representar el problema, i resolent-ho amb l'algorisme relaxation labeling; i (ii) una recerca per millorar els resultats afegint informació del mon extreta de la Wikipedia. L'aproximació presentada pot fer servir els models mention-pair i entity-mention de forma combinada evitant així els problemes que es troben moltes altres aproximacions de l'estat de l'art com per exemple: contradiccions de classificacions independents, falta de context i falta d'informació. A més a més, l'aproximació presentada permet incorporar informació afegint restriccions i s'ha fet recerca per aconseguir afegir informació del mon que millori els resultats. RelaxCor, el sistema que ha estat implementat durant la tesi per experimentar amb l'aproximació proposada, ha aconseguit uns resultats comparables als millors que hi ha a l'estat de l'art. S'ha participat a les competicions internacionals SemEval-2010 i CoNLL-2011. RelaxCor va obtenir la segona posició al CoNLL-2010.

Syftet med studien var att undersöka om bedömning av negativa beteenden, tortyr och mobbing, påverkas av mekanismerna moraliskt rättfärdigande, språklig omskrivning samt förskjutning av ansvar enligt Banduras (1986) teori om moraliskt frikopplande. Ett flerfaktoriellt experiment utfördes på 195 deltagare. Deltagarna ombads bedöma hur acceptabla negativa beteenden var, genom att läsa texter där det förekom skriftliga manipulationer av studiens oberoende variabler moraliskt rättfärdigande, språklig omskrivning samt förskjutning av ansvar. Resultatet visade att moraliskt rättfärdigande samt förskjutning av ansvar hade en effekt. Tortyr bedömdes mer acceptabelt då texten manipulerats med moraliskt rättfärdigande samt förskjutning av ansvar. Även mobbing bedömdes mer acceptabelt vid manipulation av moraliskt rättfärdigande. Dock bedömdes mobbing mindre acceptabelt vid förskjutning av ansvar än vid ingen manipulation i texten. En interaktionseffekt visades i tortyrfallet, tortyr blev mer acceptabelt när moraliskt rättfärdigande och språklig omskrivning kombinerades, än vid manipulation var för sig.

No description available.

MRI can provide anatomical, functional, and physiological images at relatively high spatial resolution and is non-invasive and does not have depth limitation. However, the application of MRI to study the retina is difficult due to the very small size of the retina. This thesis details the development of MRI methods to image blood flow (BF), anatomy, and function of the retina and choroid, and their application to two diseases of the retina: diabetic retinopathy and retinal degeneration. A unique continuous arterial spin labeling technique was developed to image BF in mice and tested by imaging cerebral BF. This method was then applied to image layer-specific BF of the retina and choroid in mice, and to acquire BF functional MRI of the retina and choroid in response to hypoxic challenge. Additionally blood oxygen level dependent functional MRI of the mouse retina and choroid in response to hypoxic challenge was obtained using a balanced steady state free precession sequence which provides fast acquisition, has high signal to noise ratio, and does not have geometric distortion or signal dropout artifacts. In a mouse model of diabetic retinopathy, MRI detected reduced retinal BF in diabetic animals. Visual function in the diabetic mice, as determined by psychophysical tests, was also reduced. Finally, in a mouse model of retinal degeneration, BF and anatomical MRI detected reductions of retinal BF and the thickness of the retina. The studies detailed in this thesis demonstrate the feasibility of layer-specific MRI to study BF, anatomy, and function, in the mouse retina. Further, these methods were shown to provide a novel means of studying animal models of retinal disease in vivo.

Development of nanostructures as MR contrast agent will significantly improve the field of disease diagnostics. Contrast agents such as iron oxide nanoparticles are less toxic compared to more commonly used gadolinium based agents. A subclass of iron based nano particles are super paramagnetic iron oxide nano particles, (SPIOs) which are widely studied MR contrast agents useful in both imaging and drug delivery applications. In this work, SPIOs were synthesized and characterized and used for cellular tracking and multi modal labeling. A new solvent exchange method was utilized to coat different core size iron oxide nano particles. SPIOs were characterized for in-vivo imaging using MR and they had a very uniform size distribution which was determine using dynamic light scattering (DLS) and transmission electron microscopy. Furthermore, blood circulation half-life of 16nm SPIOs were determined through tail vein injection. SPIOs have many applications among which is the in vivo tracking of stem cells which is critical for determination of stem cells fate after injection. Magnetic Resonance (MR) as a non-invasive method can provide significant information about the fate of the cells as well as determination of the success rate of therapeutic cellular deliveries. Mesenchymal stem cells can be loaded with super paramagnetic iron oxide nano particles (SPIOs) and have their movements followed once planted in vivo. We present our findings on the effect of SPIO concentration and stem cell density on the MR signal and transverse relaxation time. Our preliminary results indicated that SPIOs do not cause mesenchymal stem cell cytotoxicity and do not affect proliferation ability up to 200 μg/ml concentration. The release of the nanoparticles was investigated 24 hours post internalization and the result showed that SPIOs will stay inside the cell. We also found that the contrast increases in a concentration dependent manner. Our results suggest that using MR with low concentration of SPIOs is a novel and promising method for tracking of mesenchymal stem cells. In this work SPIOs were also labeled with 64Cu to investigate their potential for multi modal positron emission tomography (PET) MR imaging. Dual modality PET MR SPIO contrast agent can be synthesized to image diseases such as cancer and atherosclerosis. The advantage is the non-invasive and early detection of disease at molecular lever before it has spread to late stages or in case of the atherosclerosis before the plaque has blocked the vessel. To develop a multi modal contrast agent, a positron emitter, 64Cu (half-life of 12.701 ± 0.002 hours), was used in labeling and synthesis was performed all in one step with the addition of 64Cu chelator, 14-PE DTPA followed by radiolabeling for both 6.5nm SPIO and 17nm SPIO. After labeling and purification with the desalting column, the amount of dissociated 64Cu in the solution was determined using radio thin layer chromotagraphy (TLC) and the particle was shown to have minimum amount of fee 64Cu. Serum stability of labeled SPIO was determined in vitro by incubating 64Cu-labeled SPIOs in mouse serum at 37 °C for 24 hr with constant shaking. Radio TLC result then revealed that 64Cu stays bounded to the SPIO after 24 hours in mouse serum. This means that 64Cu labeled SPIO has a great potential as a dual modality contrast agents and further in-vivo studies are required to verify the findings.

The interaction behavior of humic acids with uranium(VI) and the influence of humic substances on the migration behavior of uranium was investigated. A main focus of this work was the synthesis of four different humic acid model substances and their characterization and comparison to the natural humic acid from Aldrich. A radiometric method for the determination of humic acid functional groups was applied in addition to conventional methods for the determination of the functionality of humic acids. The humic acid model substances show functional and structural properties comparable to natural humic acids. Modified humic acids with blocked phenolic OH were synthesized to determine the influence of phenolic OH groups on the complexation behavior of humic acids. A synthesis method for 14C-labeled humic acids with high specific activity was developed. The complexation behavior of synthetic and natural humic acids with uranium(VI) was investigated by X-ray absorption spectroscopy, laser-induced fluorescence spectroscopy and FTIR spectroscopy. The synthetic model substances show an interaction behavior with uranium(VI) that is comparable to natural humic acids. This points to the fact that the synthetic humic acids simulate the functionality of their natural analogues very well. For the first time the influence of phenolic OH groups on the complexation behavior of humic acids was investigated by applying a modified humic acid with blocked phenolic OH groups. The formation of a uranyl hydroxy humate complex was identified by laserspectroscopic investigations of the complexation of Aldrich humic acid with uranium(VI)at pH 7. The migration behavior of uranium in a sandy aquifer system rich in humic substances was investigated in column experiments. A part of uranium migrates non-retarded through the sediment, bound to humic colloids. The uranium migration behavior is strongly influenced by the kinetically controlled interaction processes of uranium with the humic colloids. The influence of humic acids on the sorption of uranium(VI) onto phyllite was investigated in batch experiments using two different humic acids. The uranium(VI) sorption onto the rock phyllite is influenced by the pH-dependent sorption behavior of the humic acids.

Photoaffinity labeling is a quintessential technique in studying and analyzing the interaction between a ligand and receptor. Diazirines are one of the important photo-labile moieties used in photoaffinity labeling due to their superior photo labeling characteristics. Herein, we report the investigations we conducted with diazirine photolabels on (a) photochemical aspects leading to enhancement of their ambient light stability and (b) equipping them with fluorous tags to enable fluorous enrichment of labeled proteins. Furthermore, we report a pilot study to develop BACE-1 inhibitors, which have potential to be developed into photoaffinity probes. 3-Trifluoromethyl-3-phenyldiazirine offers good selectivity and protection against pseudolabeling but due to its photo lability, it undergoes decomposition even under ambient light. Thus the laboratory handling, including synthesis, of 3-trifluoromethyl-3-phenyldiazirine is cumbersome and restricted under constant darkness. Herein, we have designed, synthesized and evaluated two photolabels with enhanced stability to ambient light conditions in addition to the good selectivity and protection against pseudolabeling as offered by 3-trifluoromethyl-3-phenyldiazirine. It was also found that the aqueous solubility, a vital physical property for a photolabel, was also improved in the modified ambient light stable photolabels. Fluorous tags have found wide use in synthetic applications; herein we explore the possibility of its application in photoaffinity studies. We designed, synthesized and conducted photoactivation studies on two fluorous diazirine photolabels. The photoactivation studies unraveled an unanticipated photoreaction when the fluorous tag was directly connected to the diazirine ring, yielding a fluorous alkene. The more practical photolabel of the two was chosen as the target specific photoaffinity labeling moiety for fluorous proteomics. Upon conducting photolabeling experiments under various conditions, we found that the strong hydrophobic character of the fluorous tag renders the photoaffinity label insoluble in aqueous solutions and significantly alters the binding mode and affinity of the photoaffinity label to its target receptor. A library of 1,3-disubstituted 2-propanols was combinatorially prepared and tested as small molecule inhibitors of β-secretase (BACE-1). The initial screening of the 1,3-disubstituted 2-propanol library revealed a few low micromolar inhibitors for BACE-1. The compound that showed the best activity was chosen for further SAR studies, which resulted in a potent BACE-1 inhibitor with nanomolar inhibition. Investigation on the selectivity of these compounds for BACE-1 inhibition over cathepsin D revealed that these compound series possess very high selectivity. Furthermore, the physicochemical properties study showed that these compounds possessed the calculated parameters advantageous to cross the blood-brain barrier (BBB).

De arbetssökande som har intervjuats har beskrivit att ett arbete är oerhört viktigt, för att fylla vardagen med något meningsfullt och bidra med något till omvärlden.   I tidigare forskning och dagspress har vi funnit att det kan innebära problem att få komma in på den svenska arbetsmarknaden för den individ som har ett utländsktklingande namn. Tidigare forskning visar på att det är enklare att få komma på en arbetsintervju om du har ett svensktklingande namn jämfört med ett utländsktklingande namn. Det vi vill lyfta fram i denna studie är de subjektiva upplevelserna respondenter upplever kring att vara arbetslös samt om deras namn kan utgöra ett hinder för att få komma på arbetsintervju. Denna kvalitativa studie syftar till att ta reda på om ett utländsktklingande namn har negativ påverkan på att få komma på arbetsintervju, huruvida de berörda i studien uppfattar namnets betydelse och sina egna möjligheter på arbetsmarknaden. Sex kvalitativa intervjuer har skett på Arbetsförmedlingen i Örebro. En har genomförts med en personal vid Arbetsförmedlingen och de andra fem har gjorts med individer med utländsktklingande namn som idag söker arbete.  Vårt urval har bestått av att intervjua arbetssökande individer i Örebro kommun.      Intervjuerna hade fokus på att undersöka huruvida ett utländskt namn har påverkan på individens möjligheter att få komma på arbetsintervju.   I intervjuerna har det dock framkommit att de arbetssökande anser att deras namn har viss betydelse när det gäller att få komma på arbetsintervju, ett svenskt namn väger tyngre än ett utländskt. Intervjupersonerna har påpekat att det kan vara andra attribut som spelar roll, exempelvis kultur, utbildning, utseende eller språkproblem. Arbetsgivare tar då det säkra före det osäkra, att kalla de med svenskt namn före de med utländsktklingande namn att få komma på arbetsintervju. / The applicants have described that having a job is extremely important to fill out the everyday life with something meaningful and to make a contribution to the society. From previous research and in the daily press, we have seen that in the labor market that it can be a problem if an individual has a foreign name. If you have a Swedish conformed name, it gets easier towards being called to a work interview. This study implied to study individuals with non-Swedish conformed names and their alleged difficulties with having a work interview. To contact the interview persons, help have been handed from the Work Employment Agency in Örebro, Sweden. Six qualitative interviews have been performed; five of these have been with individuals with foreign names, that currently are searching for work and one of these has been with one of the staff at the agency. The interviews have revealed that the name had some significance when it comes to being called to a work interview. A Swedish conformed name outweighs a foreign name in some cases. During the interviews focus was laid on how the applicants described their feelings and experiences of being declined a work interview because of their foreign names.  The interviewees pointed out that there may be other attributes that are important; such as culture, education, appearance or language difficulties. Employers will then rather be safe than sorry, therefore, they call those with Swedish conformed names instead of those with foreign names.

Investigation of RNA and DNA function often requires sequence-specific incorporation of various reporter and affinity probes. This can be achieved using AdoMet-dependent methyltransferases (MTases) as they can be active with synthetic AdoMet analogues equipped with transferable chains larger than the methyl group. These chains usually carry reactive groups that can be further chemically appended with required reporters. For this, azide-alkyne 1,3-cycloaddition (AAC), also called “click”, reaction is particularly attractive. This work shows that the HhaI cytosine-5 DNA MTase (variant Q82A/Y254S/N204A) catalyzes efficient sequence-specific transfer of hex-2-ynyl side chains containing terminal alkyne or azide groups from synthetic cofactor analogues to DNA. Both the enzymatic transfer and subsequent “click” coupling of a fluorophore can be performed even in cell lysates. For RNA labeling, the activity of an archaeal RNA 2‘-O-MTase C/D ribonucleoprotein complex (RNP) with synthetic cofactors was investigated. It was shown that synthetically reprogrammed guide RNA sequences can be used to direct the C/D RNP-dependent transfer of a prop-2-ynyl group to predetermined nucleotides in substrate RNAs. Followed by AAC this can be used for programmable sequence-specific labeling of a variety of RNA substrates in vitro. These new possibilities for specific labeling of nucleic acids can be adopted in biochemistry, biomedical, nanotechnology, etc. research. / Tiriant DNR ir RNR, neretai svarbu prijungti įvairius reporterinius ar giminingumo žymenis griežtai apibrėžtose (sekos) vietose – t.y. specifiškai. Tam galima pasitelkti fermentus metiltransferazes (MTazes). Natūraliai jos naudoja kofaktorių AdoMet, tačiau gali būti aktyvios ir su sintetiniais jo analogais, turinčiais ilgesnes nei metil- pernešamas grandines. Jei šios grandinės turi galines funkcines grupes, prie jų vėliau cheminių reakcijų pagalba galima prijungti norimus žymenis. Tam itin patogi azidų-alkinų cikloprijungimo (AAC), dar vadinama „click“, reakcija. Šiame darbe parodyta, kad DNR citozino-5 MTazė HhaI (variantas Q82A/Y254S/N204A) efektyviai katalizuoja sekai specifinę heks-2-inil- grandinių, turinčių galines alkinil- arba azido- grupes, pernašą nuo sintetinių kofaktorių ant DNR. Naudojant šią MTazės-kofaktorių sistemą bei AAC, visą specifinio DNR žymėjimo procesą galima atlikti netgi ląstelių lizate. RNR žymėjimui ištirtas archėjų RNR 2‘-O-MTazės C/D ribonukleoproteininio komplekso aktyvumas su sintetiniais kofaktoriais. Parodyta galimybė sintetiškai keičiant kreipiančiąją RNR, prop-2-inilgrupės pernašą nukreipti į norimas įvairių substratinių RNR sekos vietas ir po to AAC reakcijos pagalba prijungti fluoroforą. Taigi, sukurtas naujas molekulinis įrankis, leidžiantis be suvaržymų pasirinkti norimą pažymėti RNR seką. Šios naujos specifinio nukleorūgščių žymėjimo galimybės gali būti pritaikytos biochemijos, biomedicinos, nanotechnologijų ir kitose tyrimų srityse... [toliau žr. visą tekstą]

Tiriant DNR ir RNR, neretai svarbu prijungti įvairius reporterinius ar giminingumo žymenis griežtai apibrėžtose (sekos) vietose – t.y. specifiškai. Tam galima pasitelkti fermentus metiltransferazes (MTazes). Natūraliai jos naudoja kofaktorių AdoMet, tačiau gali būti aktyvios ir su sintetiniais jo analogais, turinčiais ilgesnes nei metil- pernešamas grandines. Jei šios grandinės turi galines funkcines grupes, prie jų vėliau cheminių reakcijų pagalba galima prijungti norimus žymenis. Tam itin patogi azidų-alkinų cikloprijungimo (AAC), dar vadinama „click“, reakcija. Šiame darbe parodyta, kad DNR citozino-5 MTazė HhaI (variantas Q82A/Y254S/N204A) efektyviai katalizuoja sekai specifinę heks-2-inil- grandinių, turinčių galines alkinil- arba azido- grupes, pernašą nuo sintetinių kofaktorių ant DNR. Naudojant šią MTazės-kofaktorių sistemą bei AAC, visą specifinio DNR žymėjimo procesą galima atlikti netgi ląstelių lizate. RNR žymėjimui ištirtas archėjų RNR 2‘-O-MTazės C/D ribonukleoproteininio komplekso aktyvumas su sintetiniais kofaktoriais. Parodyta galimybė sintetiškai keičiant kreipiančiąją RNR, prop-2-inilgrupės pernašą nukreipti į norimas įvairių substratinių RNR sekos vietas ir po to AAC reakcijos pagalba prijungti fluoroforą. Taigi, sukurtas naujas molekulinis įrankis, leidžiantis be suvaržymų pasirinkti norimą pažymėti RNR seką. Šios naujos specifinio nukleorūgščių žymėjimo galimybės gali būti pritaikytos biochemijos, biomedicinos, nanotechnologijų ir kitose tyrimų srityse... [toliau žr. visą tekstą] / Investigation of RNA and DNA function often requires sequence-specific incorporation of various reporter and affinity probes. This can be achieved using AdoMet-dependent methyltransferases (MTases) as they can be active with synthetic AdoMet analogues equipped with transferable chains larger than the methyl group. These chains usually carry reactive groups that can be further chemically appended with required reporters. For this, azide-alkyne 1,3-cycloaddition (AAC), also called “click”, reaction is particularly attractive. This work shows that the HhaI cytosine-5 DNA MTase (variant Q82A/Y254S/N204A) catalyzes efficient sequence-specific transfer of hex-2-ynyl side chains containing terminal alkyne or azide groups from synthetic cofactor analogues to DNA. Both the enzymatic transfer and subsequent “click” coupling of a fluorophore can be performed even in cell lysates. For RNA labeling, the activity of an archaeal RNA 2‘-O-MTase C/D ribonucleoprotein complex (RNP) with synthetic cofactors was investigated. It was shown that synthetically reprogrammed guide RNA sequences can be used to direct the C/D RNP-dependent transfer of a prop-2-ynyl group to predetermined nucleotides in substrate RNAs. Followed by AAC this can be used for programmable sequence-specific labeling of a variety of RNA substrates in vitro. These new possibilities for specific labeling of nucleic acids can be adopted in biochemistry, biomedical, nanotechnology, etc. research.