1,232 research outputs found

    Investigating the impacts of training data set length (T) and the aggregation unit size (M) on the accuracy of the self-exciting point process (SEPP) hotspot method

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    This study examines the impacts of two variables; the training data lengths (T) and the aggregation unit sizes (M); on the accuracy of the self-exciting point process (SEPP) model during crime prediction. A case study of three crime types in the South Chicago area is presented, in which different combinations of values of T and M are used for 100 daily consecutive crime predictions. The results showed two important points regarding the SEPP model: first is that large values of T are likely to improve the accuracy of the SEPP model and second is that, a small aggregation unit, such as a 50m x 50m grid, is better in terms of capturing local repeat and near-repeat patterns of crimes

    Forkhead transcription factor FOXO3a levels are increased in Huntington disease because of overactivated positive autofeedback loop

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    Huntington disease (HD) is a fatal autosomal dominant neurodegenerative disorder caused by an increased number of CAG repeats in the HTT gene coding for huntingtin. Decreased neurotrophic support and increased mitochondrial and excitotoxic stress have been reported in HD striatal and cortical neurons. The members of the class O forkhead (FOXO) transcription factor family, including FOXO3a, act as sensor proteins that are activated upon decreased survival signals and/or increased cellular stress. Using immunocytochemical screening in mouse striatal Hdh7/7 (wild type), Hdh7/109 (heterozygous for HD mutation), and Hdh109/109 (homozygous for HD mutation) cells, we identified FOXO3a as a differentially regulated transcription factor in HD. We report increased nuclear FOXO3a levels in mutant Hdh cells. Additionally, we show that treatment with mitochondrial toxin 3-nitropropionic acid results in enhanced nuclear localization of FOXO3a in wild type Hdh7/7 cells and in rat primary cortical neurons. Furthermore, mRNA levels of Foxo3a are increased in mutant Hdh cells compared with wild type cells and in 3-nitropropionic acid-treated primary neurons compared with untreated neurons. A similar increase was observed in the cortex of R6/2 mice and HD patient post-mortem caudate tissue compared with controls. Using chromatin immunoprecipitation and reporter assays, we demonstrate that FOXO3a regulates its own transcription by binding to the conserved response element in Foxo3a promoter. Altogether, the findings of this study suggest that FOXO3a levels are increased in HD cells as a result of overactive positive feedback loop

    Problems in contemporary surgery : dedicated to Ulrich Karell's 100-th anniversary

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    • H. Kelk. Professor Ulrich Karell • L. Roostar. Professor U. Karell, Head of Tartu University hospital of surgery 1931-1944 • A. Peetsalu. Professor Ulrich Karell's scientific papers on abdominal surgery. Survey • J. Soplepmann, A. Peetsalu, M. Peetsalu, Т. Väli, A. Tein. Endoscopic findings in upper gastrointestinal tract hemorrhage in Tartu University surgical clinic: comparison of two periods, 1979-81 and 1989-91 • T. Varnja, M. Peetsalu, A. Peetsalu. Long-term results of proximal vagotomy and duodenoplasty in the treatment of duodenal obstruction • E. Sepp, P. Pree, P. Roosaar, M. Raag. Cytologic analysis concerning the influence of exogenous prostaglandins (PGE2) and vagotomy on some organs of the gastrointestinal tract • T. Väli, A. Tamm. Diagnostic criteria for lactose loading test after gastric surgery • L. Roostar, M. Murruste. Surgery of large bowel gunshot injuries • R. Rander, A. Loog. Т.-A. Suiting, T. Meren, A. Paa ps tel, R. Annus, M. Alver. Early mortality after 189 coronary bypass operations for acute myocardial infarction. Risk Factors and optimal timing • R. Paju, R. Kolk. Efficacy of transesophageal rapid left atrial pacing for termination of type I atrial flutter • R. Kolk, I. Roose. Comparative long-term follow-up of atrial and ventricular paced patients with symptomatic sick sinus syndrome • R. Tikk, A. Peetsalu. Epidemiology and surgical treatment of cholelithiasis in II surgical department of Tartu University hospital in 1979-1992 • H. Seepter, H. Tikko, H. Kokk, U. Lepner, R. Lumiste, Т. Vaasna. Management of benign biliary obstruction • P. Dmitriev, A. Lõhmus. A. Linnamäe. 25 years of renal transplantation in Tartu • Т. Väli, А. Peetsalu, А. Kõrgvee, Т. Tikk, A. Tein, J. Soplepmann, T. Vardja, K. Kokk, U. Sule. Experimental liver transplantation in Estonia as preparation for clinical liver transplantation Preliminary report. • E. Teeäär. Some aspects of the development of thyroid surgery in Estonia • E. Rebane, H. Tikko, E. Tünder, О. vasar, U. Lepner, A. Helberg, A. Pulges, T. Vaasna, J. Lieberg, S. Subo, T. Ellervee, V. Tamm, N. Põdramägi. Results of femoropopliteal and synchronous combined aortofemoral/femoropopliteal bypasses. • U. Lepner, H. Tikko, E. Rebane, V. Tamm. The management of occluded aortofemoral graft limb • O. Vasar, E. Tünder, N. Põdramägi. Surgical treatment of critical leg ischaemia in patients with multisegmental atherosclerosis • O. Milenin, E. Tünder, Ü. Hussar, T. Sillakivi, A. Pille. Comparison of different experimental models of transplantation of a segment of small intestine on vascularized pedicle • O. Milenin, E. Tünder. Ü. Hussar, T. Sillakivi. Split ileum freetissue transfer in oesophageal reconstruction • W. Haße. Treatment of oesophageal atresia • W. Haße. Clinical experience of treating omphalocele gastroscisis • (1962-1991) • M. Viigimaa, M. Zemtsovsky, U. Kiho. Prophylaxis of venous thromboembolism in orthopaedic surgeryhttp://tartu.ester.ee/record=b1076453~S1*es

    Palverändurite usundilised arusaamad Santiago de Compostela ja Glastonbury palverännakust: välitööpõhiseid käsitlusi

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    Väitekirja elektrooniline versioon ei sisalda publikatsioone.Väitekiri käsitleb tänapäevase Euroopa rahvausundi ja nüüdisaegse palverännaku erinevaid aspekte Põhja-Hispaanias kulgeva Camino de Santiago (püha Jaakobuse tee) ja Edela-Inglismaal asuva Glastonbury näitel. Palverändu vaadeldakse kui jutustatud teekonda, kus juhtuvad imed ja toimuvad kohtumised üleloomulike olenditega: erineva religioosse taustaga palverändurid räägivad endaga juhtunud lugusid, muistendeid ja legende. Tähelepanu all on ka palverännakul valitsevad võimusuhted ja palverändurite hierarhia. Üks lugude läbivaid teemasid on autentse palveränduri identiteedi konstrueerimine; otsitakse vastust küsimusele, kellel on õigus otsustada selle üle, kes on tõeline palverändur, ning milliste põhjenduste kaudu otsus tehakse. Autori eesmärgiks ei ole mõisteid „palverännak“ ja „palverändur“ defineerida, vaid vaadelda nende tähendusvälja muutumist nii akadeemilises kui ka rahvapärases diskursuses. Uurimus kajastab ka erinevate uskumissüsteemide, eriti katoliikluse ja New Age’i kokkupõrkeid. Uurija tähelepanu all on inimesed ja nende usundilised praktikad, mitte „religioon“ ja „usk“ kui abstraktsioonid. Uuritakse seda, kuidas religiooni kogetakse ja praktiseeritakse nii üksikisiku kui ka kogukonna tasandil. Käsitletakse ka välitööde metodoloogia probleeme, eriti uurija rolli dialoogilises tööprotsessis. Töö põhiliseks allikaks on välitööd Camino de Santiagol ja Glastonburys. Väitekirja moodustavad sissejuhatus ja neli artiklit, mis on ilmunud rahvusvahelise levikuga publikatsioonides (Journal of Indian Folkloristics, Journal of Ethnology and Folkloristics) ja kirjastuse Equinox kogumikus Vernacular Religion in Everyday Life. Lisaks väitekirja aluseks olevatele artiklitele on Tiina avaldanud kaks raamatut, kus käsitleb oma välitööde kogemusi: „Peregrina päevik“ ilmus 2007. aastal Loomingu Raamatukogus; selle järjena ilmus 2009. aastal „Kas jääte ööseks? Hospitalera päevik“.This dissertation is based on the author’s extensive fieldwork conducted in two important destinations in the spiritual landscape of European vernacular religion – the Camino de Santiago in northern Spain and Glastonbury in southwest England. One of the aims of this dissertation is to provide insight into the phenomenon of contemporary pilgrimage while reflecting upon fieldwork experiences. One of the recurrent themes is the construction of the image of the ‘authentic’ pilgrim. The research has been carried out in the broad framework of vernacular religion, i.e. religion as it is experienced and practiced rather than as it is prescribed. By looking at the wide range of belief narratives expressed by pilgrims, Tiina Sepp studies pilgrimage as a narrated journey, including miracles and supernatural encounters. The co-existence of the different belief systems of Christianity and New Age and the conflicts and tension between them are explored. Throughout her fieldwork Tiina Sepp has observed people’s attitudes towards pilgrimage and their fellow pilgrims. By looking at different, competing narratives about the Camino de Santiago and Glastonbury, she looks into the power relationships that exist on the pilgrimage, describes how hierarchies of pilgrims are created and maintained, and reflects on the meaning of the words pilgrim and pilgrimage. With her markedly self-reflexive methodology, the author attempts to give voice to as many different people as possible: many primary narratives have been reproduced. The dissertation consists of an introduction and four articles that have been published in the international publications the Journal of Indian Folkloristics and the Journal of Ethnology and Folkloristics, as well as in Vernacular Religion in Everyday Life (a collection of articles published by Equinox). In addition to these four articles, Tiina Sepp has published two books in Estonian that deal with her fieldwork experiences

    De Natuurlyke Historie Der Versteeningen Of Uitvoerige Afbeelding En Beschryving Van De Versteende Zaaken, Die Tot Heden Op Den Aardbodem Zyn Ontdekt / Aangevangen Door Georg Wolfgang Knorr Vervolgd En Omstandig Beredeneerd Door Johann Ernst Immanuel Walch ... Uit Het Hoog- In 'T Nederduitsch Vertaald Door M. Houttuyn ... ; Eerste Deel

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    DE NATUURLYKE HISTORIE DER VERSTEENINGEN OF UITVOERIGE AFBEELDING EN BESCHRYVING VAN DE VERSTEENDE ZAAKEN, DIE TOT HEDEN OP DEN AARDBODEM ZYN ONTDEKT / AANGEVANGEN DOOR GEORG WOLFGANG KNORR VERVOLGD EN OMSTANDIG BEREDENEERD DOOR JOHANN ERNST IMMANUEL WALCH ... UIT HET HOOG- IN 'T NEDERDUITSCH VERTAALD DOOR M. HOUTTUYN ... ; EERSTE DEEL De Natuurlyke Historie Der Versteeningen Of Uitvoerige Afbeelding En Beschryving Van De Versteende Zaaken, Die Tot Heden Op Den Aardbodem Zyn Ontdekt / Aangevangen Door Georg Wolfgang Knorr Vervolgd En Omstandig Beredeneerd Door Johann Ernst Immanuel Walch ... Uit Het Hoog- In 'T Nederduitsch Vertaald Door M. Houttuyn ... (-) De Natuurlyke Historie Der Versteeningen Of Uitvoerige Afbeelding En Beschryving Van De Versteende Zaaken, Die Tot Heden Op Den Aardbodem Zyn Ontdekt / Aangevangen Door Georg Wolfgang Knorr Vervolgd En Omstandig Beredeneerd Door Johann Ernst Immanuel Walch ... Uit Het Hoog- In 'T Nederduitsch Vertaald Door M. Houttuyn ... ; Eerste Deel (D. 1) (1) Cover (1) Exlibris (7) Afbeeding der Marmer-Groeve (13) Frontispiz (17) Titelblatt (18) Widmung (20) Voorrede (22) Naam-lyst der heeren intekenaaren (29) Korte inhoud van dit werk (30) Eerste deels eerste verzameling, van zeldzaamheden der natuur (36) Eerste deels tweede verzameling, van zeldzaamheden der natuur (52) Eerste deels derde verzameling, van zeldzaamheden der natuur (65) En oudheden des aardbodems beschryving van een nieuw plantdier (82) Tab. I - X.c. (100) Tab. XI - XX (136) Tab. XXI - XXX (179) Tab. XXXI - XXXVIII (210

    De Natuurlyke Historie Der Versteeningen Of Uitvoerige Afbeelding En Beschryving Van De Versteende Zaaken, Die Tot Heden Op Den Aardbodem Zyn Ontdekt / Aangevangen Door Georg Wolfgang Knorr Vervolgd En Omstandig Beredeneerd Door Johann Ernst Immanuel Walch ... Uit Het Hoog- In 'T Nederduitsch Vertaald Door M. Houttuyn ... ; Tweede Deel

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    DE NATUURLYKE HISTORIE DER VERSTEENINGEN OF UITVOERIGE AFBEELDING EN BESCHRYVING VAN DE VERSTEENDE ZAAKEN, DIE TOT HEDEN OP DEN AARDBODEM ZYN ONTDEKT / AANGEVANGEN DOOR GEORG WOLFGANG KNORR VERVOLGD EN OMSTANDIG BEREDENEERD DOOR JOHANN ERNST IMMANUEL WALCH ... UIT HET HOOG- IN 'T NEDERDUITSCH VERTAALD DOOR M. HOUTTUYN ... ; TWEEDE DEEL De Natuurlyke Historie Der Versteeningen Of Uitvoerige Afbeelding En Beschryving Van De Versteende Zaaken, Die Tot Heden Op Den Aardbodem Zyn Ontdekt / Aangevangen Door Georg Wolfgang Knorr Vervolgd En Omstandig Beredeneerd Door Johann Ernst Immanuel Walch ... Uit Het Hoog- In 'T Nederduitsch Vertaald Door M. Houttuyn ... (-) De Natuurlyke Historie Der Versteeningen Of Uitvoerige Afbeelding En Beschryving Van De Versteende Zaaken, Die Tot Heden Op Den Aardbodem Zyn Ontdekt / Aangevangen Door Georg Wolfgang Knorr Vervolgd En Omstandig Beredeneerd Door Johann Ernst Immanuel Walch ... Uit Het Hoog- In 'T Nederduitsch Vertaald Door M. Houttuyn ... ; Tweede Deel (D. 2) (1) Cover (1) Exlibris (7) Titelblatt (12) Widmung (14) Eerste hoofdstuk, van de Conchyliologie (18) Het tweede Hoofdstuk, handelende van de Ammonieten en Nautilieten (52) Derde hoofdstuk, van de Orthokeratieten, Lituieten en Helicieten (69) Vierde hoofdstuk van verscheiderley versteende schulpen (81) Vyfde hoofdstuk van de eigentlyk zogenaamde versteende Cochlieten (112) Het zesde hoofdstuk van verscheiderley versteende Hoorens (123) Het zevende hoofdstuk van de versteende Schroefhoorens (137) Het agtste hoofdstuk van de Ostracieten (147) Het negende hoofdstuk van de Echinieten (168) Tab. I, I.a., A - A.VIII. (200) Tab. B. - B.VII. (226) Tab. C. - C.VIII. (276) Tab. D. - D.XIII. (306) Tab. E. - E.VI. (350

    Utilising stimulated raman scattering microscopy to study intracellular distribution of label-free ponatinib in live cells

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    Despite advancements in the drug discovery process, drug attrition rate in the late stages of clinical trials still remains high. Better understanding of drug efficacy in the pre-clinical stage would potentially translate into increased clinical trial success rate and reduce the economic burden of failed trials. However, visualising intracellular drug uptake and distribution at high resolution to improve the pre-clinical drug discovery process is still a challenge for scientists. Stimulated Raman scattering (SRS) microscopy represents a powerful imaging tool for visualising drug molecules inside cells with high resolution, without the need for additional labels, or nanoparticle sensors as used in many other optical imaging technologies. It provides Raman imaging with minimal spectral distortion and a quantitative output, allowing accurate determination of intracellular drug concentrations. Ponatinib is a clinically approved tyrosine kinase inhibitor that targets BCR-ABL and is used to treat chronic myeloid leukaemia (CML). Drug resistance is a widespread problem in CML treatment, where ponatinib resistant patients have very limited treatment options. Ponatinib has an alkyne moiety in its structure that makes it inherently Raman active in the cellular silent region of the Raman spectrum. In this thesis, SRS microscopy was used to image intracellular ponatinib label-free with high sensitivity and specificity in live human CML cell lines, in the context of ponatinib resistance. SRS imaging of ponatinib was optimised in Chapter 3, enabling ponatinib imaging at nanomolar treatment concentrations as well as determination of absolute ponatinib concentrations in both ponatinib sensitive and resistant CML cells. In Chapter 4, it was determined that ponatinib is sequestered into the lysosomes, with a higher lysosomal concentration found in drug resistant cells. This was associated with increased lysosome biogenesis. Target engagement studies showed that treatment with chloroquine reduced ponatinib accumulation in lysosomes, but did not resensitise cells to ponatinib, confirming a BCR-ABL independent resistance mechanism in this CML cell model. To demonstrate further utility of SRS microscopy, it was applied to spheroid imaging in Chapter 5. CML cell lines formed three-dimensional (3D) cell ‘aggregates’ rather than spheroids with tight cell-cell contacts, and could not be used for SRS imaging. However, spheroid growth was successfully optimised in a breast cancer cell line T47D; and live T47D spheroids were imaged using SRS microscopy
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