Till Kleopatras försvar. Att översätta en retorisk text

Historical novels as well as biographies often have a rethorical approach. People are accused. and. defended. This paper discusses the argumentative aspects of Cleopatra – a Life, written by the American Stacy Schiff. Using the analytical method in Vägar genom texten (Roads Through the Text) in which Lennart Hellspong and Per Ledin look into texts from the points of view of language, contents and the relation between the writer and the reader I have come to the conclusion that the argumentation shows at all levels of the text. The paper also points at some problems when translating from English into Swedish. The two languages have different possibilities at the semantic level as well as at the level of sentence

Dietary differences between elderly Iranians living in Sweden and Iran a cross-sectional comparative study

<p>Abstract</p> <p>Background</p> <p>During the last decades, global migration has increased and many immigrant groups have a higher prevalence than the native born population of several cardiovascular disease risk factors, including poor dietary habits. However, it is uncertain if dietary habits in immigrant populations reflect dietary habits in their country of origin or if the current diet is a consequence of the migration and possible change of dietary habits. The aim of this study was to examine possible dietary differences between elderly Iranians living in Stockholm, Sweden with elderly Iranians living in Tehran, Iran, taking into account sex, age, marital status, and education.</p> <p>Methods</p> <p>Dietary intakes were assessed by semi - quantitative food frequency questionnaire in a cross-sectional study of 121 Iranians living in Stockholm and 52 Iranians living in Tehran, aged 60-80. Differences in dietary habits between the two groups was analysed by bootstrapped regression analyses with 1000 replications.</p> <p>Results</p> <p>Iranians living in Sweden had significantly higher intake of protein, total fat, fiber than Iranians living in Iran, but lower consumption of carbohydrates. The observed differences in intake of macronutrients were reflected in consumed amount of all food items, which were higher among Iranians living in Iran with the exception of bread and grain consumption which was lower.</p> <p>Conclusions</p> <p>There are general differences in dietary habits between Iranians living in Iran and Iranians living in Sweden. Parts of observed differences in dietary habits may reflect a favourable adoption process to the Swedish dietary habits after migration. Meanwhile other differences are point of concern in light of the high prevalence of overweight, among Iranians living in Sweden and can have unfavourable impact in particular in the context of cardiovascular health.</p

In the eye of the storm : The auditor's role in the review of bonus and incentive programs

Bakgrund och problem: Sedan 1990-talet har bonus- och incitamentsprogramskandaler avlöst varandra. Detta fenomen har lett till ett minskat förtroende för näringslivets ersättningssystem varvid bonus- och incitamentsprogram av många ses som något negativt. Mediarapportering och efterföljande debatt rörande dessa skandaler behandlar sällan revisorns skyldigheter och ansvar vid godkännandet av företagets förvaltning i dessa fall trots att det i RS 310 framgår att revisorn ska granska dessa avtal. Frågan är hur det kommer sig att revisorn inte ifrågasätts i större utsträckning i de skandaler som uppdagats på senare tid?   Syfte: Att skapa en ökad förståelse för samt undersöka attityden till revisorns roll och ansvar beträffande bonus- och incitamentsprogram.   Metod: Uppsatsen är inspirerad av den hermeneutiska tolkningsmetoden där förståelsen är det centrala. Datainsamlingen är av kvalitativ karaktär och har gjorts med hjälp av semistrukturerade intervjuer både besöksintervjuer och telefonintervjuer.   Slutsatser: De två frågeställningarna i uppsatsen fick inga entydiga svar. Hur det kommer sig att revisorn inte ifrågasätts i större utsträckning i den senaste tidens skandaler kan enligt vissa respondenter bero på att revisorn felfritt skött sitt jobb och att det därför inte finns någon anledning att skriva om honom/henne. Andra respondenter menar att det är ett problem. Vilka problem revisorn ställs inför när principer ska möta verkligheten vid granskning av bonus- och incitamentsprogram tros enligt empirin främst vara den luddighet som uppstår vid principbaserade revisionsstandarder. En annan orsak kan vara det vänskapshot som kan uppstå i relationen mellan revisor och företag. Vad oenigheterna i respondenternas svar beror på är svårt att säga, det kan finnas många bakomliggande orsaker såsom olika förväntan på vad revisorn ska uträtta vid revision samt att revisorns regler till viss del är vaga och lite otydliga

IAS 36 punkt 134 : upplysningskrav rörande nedskrivningstest av goodwill

1 januari 2005 infördes nya redovisningsstandarder enligt IFRS/IAS. Alla börsnoterade bolag inom EU skall tillämpa de nya redovisningsreglerna. Syftet med införandet av de internationella redovisningsreglerna var att göra de finansiella rapporterna mer internationellt gångbara och jämförbara samt bidra till en mer rättvisande bild av företagets tillgångar. Uppsatsen granskar om företag uppfyller upplysningskraven enligt IAS 36 punkt 134 rörande att immateriella tillgångar med obestämbar nyttjandeperiod inte längre skrivs av utan årligen nedskrivningsprövas. Vi genomförde en undersökning av totalt tjugo företag från IT- och läkemedelsbranschen med redovisad goodwillpost. Vi granskade företagens årsredovisningar utifrån vår tolkningsmall av IAS 36 punkt 134. Baserat på resultatet av vår empiriska studie har vi bildat oss uppfattningen att det förekommer brister i företagens upplysningar. Vi har även genomfört samma undersökning på företagens årsredovisningar för 2005. Syftet var att ta reda på om någon förbättring gick att se då tidigare publicerad undersökning och artikel förutspått detta. Enligt vår studie har ingen märkbar förändring skett. Anledningen till att kraven inte uppfylls i större utsträckning tror vi kan vara en kombination av okunskap och svårigheter att tolka regelverket samt i vissa fall ovilja att lämna ut känslig information. Vår bedömning är att syftet med införandet av de nya standarderna inte uppnås i den utsträckning som vore önskvärd. Vi anser att de nya reglerna medför en mer subjektiv redovisning vilket minskar trovärdigheten och jämförbarheten. Målet med en mer rättvisande bild menar vi i vissa fall får stå tillbaka för försiktighetsprincipen

Stability Enhancement of a Dimeric HER2-Specific Affibody Molecule through Sortase A-Catalyzed Head-to-Tail Cyclization

Natural backbone-cyclized proteins have an increased thermostability and resistance towards proteases, characteristics that have sparked interest in head-to-tail cyclization as a method to stability-enhance proteins used in diagnostics and therapeutic applications, for example. In this proof-of principle study, we have produced and investigated a head-to-tail cyclized and HER2-specific ZHER2:342 Affibody dimer. The sortase A-mediated cyclization reaction is highly efficient (&gt;95%) under optimized conditions, and renders a cyclic ZHER3:342-dimer with an apparent melting temperature, Tm, of 68 °C, which is 3 °C higher than that of its linear counterpart. Circular dichroism spectra of the linear and cyclic dimers looked very similar in the far-UV range, both before and after thermal unfolding to 90 °C, which suggests that cyclization does not negatively impact the helicity or folding of the cyclic protein. The cyclic dimer had an apparent sub-nanomolar affinity (Kd ~750 pM) to the HER2-receptor, which is a ~150-fold reduction in affinity relative to the linear dimer (Kd ~5 pM), but the anti-HER2 Affibody dimer remained a high-affinity binder even after cyclization. No apparent difference in proteolytic stability was detected in an endopeptidase degradation assay for the cyclic and linear dimers. In contrast, in an exopeptidase degradation assay, the linear dimer was shown to be completely degraded after 5 min, while the cyclic dimer showed no detectable degradation even after 60 min. We further demonstrate that a site-specifically DyLight 594-labeled cyclic dimer shows specific binding to HER2-overexpressing cells. Taken together, the results presented here demonstrate that head-to-tail cyclization can be an effective strategy to increase the stability of an Affibody dimer

Feasibility of Affibody Molecule-Based PNA-Mediated Radionuclide Pretargeting of Malignant Tumors

Affibody molecules are small (7 kDa), non-immunoglobulin scaffold proteins with a potential as targeting agents for radionuclide imaging of cancer. However, high renal re-absorption of Affibody molecules prevents their use for radionuclide therapy with residualizing radiometals. We hypothesized that the use of Affibody-based peptide nucleic acid (PNA)-mediated pretargeting would enable higher accumulation of radiometals in tumors than in kidneys. To test this hypothesis, we designed an Affibody-PNA chimera ZHER2:342-SR-HP1 containing a 15-mer HP1 PNA recognition tag and a complementary HP2 hybridization probe permitting labeling with both (125)I and (111)In. (111)In-ZHER2:342-SR-HP1 bound specifically to HER2-expressing BT474 and SKOV-3 cancer cells in vitro, with a KD of 6±2 pM for binding to SKOV-3 cells. Specific high affinity binding of the radiolabeled complementary PNA probe (111)In-/(125)I-HP2 to ZHER2:342-SR-HP1 pre-treated cells was demonstrated. (111)In-ZHER2:342-SR-HP1 demonstrated specific accumulation in SKOV-3 xenografts in BALB/C nu/nu mice and rapid clearance from blood. Pre-saturation of SKOV-3 with non-labeled anti-HER2 Affibody or the use of HER2-negative Ramos xenografts resulted in significantly lower tumor uptake of (111)In-ZHER2:342-SR-HP1. The complementary PNA probe (111)In/(125)I-HP2 accumulated in SKOV-3 xenografts when ZHER2:342-SR-HP1 was injected 4 h earlier. The tumor accumulation of (111)In/(125)I-HP2 was negligible without ZHER2:342-SR-HP1 pre-injection. The uptake of (111)In-HP2 in SKOV-3 xenografts was 19±2 %ID/g at 1 h after injection. The uptake in blood and kidneys was approximately 50- and 2-fold lower, respectively. In conclusion, we have shown that the use of Affibody-based PNA-mediated pretargeting enables specific delivery of radiometals to tumors and provides higher radiometal concentration in tumors than in kidneys.De två första författarna delar förstaförfattarskapet och de två sista författarna delar sistaförfattarskapet.</p

Site-specific conjugation of recognition tags to trastuzumab for peptide nucleic acid-mediated radionuclide HER2 pretargeting

Pretargeting is a promising strategy to reach high imaging contrast in a shorter time than by targeting with directly radiolabeled monoclonal antibodies (mAbs). One of problems in pretargeting is a site-specific, reproducible and uniform conjugation of recognition tags to mAbs. To solve this issue we propose a photoconjugation to covalently couple a recognition tag to a mAb via a photoactivatable Z domain. The Z-domain, a 58-amino acid protein derived from the IgG-binding B-domain of Staphylococcus aureus protein A, has a well-characterized binding site in the Fc portion of IgG. We tested the feasibility of this approach using pretargeting based on hybridization between peptide nucleic acids (PNAs). We have used photoconjugation to couple trastuzumab with the PNA-based hybridization probe, HP1. A complementary [Co-57]Co-labeled PNA hybridization probe ([Co-57]Co-HP2) was used as the secondary targeting probe. In vitro studies demonstrated that trastuzumab-ZHP1 bound specifically to human epidermal growth factor receptor 2 (HER2)-expressing cells with nanomolar affinity. The binding of the secondary [Co-57]Co-HP2 probe to trastuzumab-PNA-pretreated cells was in the picomolar affinity range. A two-fold increase in SKOV-3 tumor targeting was achieved when [Co-57]Co-HP2 (0.7 nmol) was injected 48 h after injection of trastuzumab-ZHP1 (0.5 nmol) compared with trastuzumab-ZHP1 alone (0.8 +/- 0.2 vs. 0.33 +/- 0.06 %ID/g). Tumor accumulation of [Co-57]Co-HP2 was significantly reduced by pre-saturation with trastuzumab or when no trastuzumab-ZHP1 was preinjected. A tumor-to-blood uptake ratio of 1.5 +/- 0.3 was achieved resulting in a clear visualization of HER2-expressing xenografts as confirmed by SPECT imaging. In conclusion, the feasibility of stable site-specific coupling of a PNA-based recognition tag to trastuzumab and successful pretargeting has been demonstrated. This approach can hopefully be used for a broad range of mAbs and recognition tags

Evaluation of an antibody-PNA conjugate as a clearing agent for antibody-based PNA-mediated radionuclide pretargeting

Radionuclide molecular imaging of cancer-specific targets is a promising method to identify patients for targeted antibody therapy. Radiolabeled full-length antibodies however suffer from slow clearance, resulting in high background radiation. To overcome this problem, a pretargeting system based on complementary peptide nucleic acid (PNA) probes has been investigated. The pretargeting relies on sequential injections of primary, PNA-tagged antibody and secondary, radiolabeled PNA probe, which are separated in time, to allow for clearance of non-bound primary agent. We now suggest to include a clearing agent (CA), designed for removal of primary tumor-targeting agent from the blood. The CA is based on the antibody cetuximab, which was conjugated to PNA and lactosaminated by reductive amination to improve hepatic clearance. The CA was evaluated in combination with PNA-labelled trastuzumab, T-ZHP1, for radionuclide HER2 pretargeting. Biodistribution studies in normal mice demonstrated that the CA cleared ca. 7 times more rapidly from blood than unmodified cetuximab. Injection of the CA 6 h post injection of the radiolabeled primary agent [131I]I-T-ZHP1 gave a moderate reduction of the radioactivity concentration in the blood after 1 h from 8.5 ± 1.8 to 6.0 ± 0.4%ID/g. These proof-of-principle results could guide future development of a more efficient CA.De två första författarna delar förstaförfattarskapetDe två sista författarna delar sistaförfattarskapet</p

Development of an optimal imaging strategy for selection of patients for affibody-based PNA-mediated radionuclide therapy

Affibody molecules are engineered scaffold proteins, which demonstrated excellent binding to selected tumor-associated molecular abnormalities in vivo and highly sensitive and specific radionuclide imaging of Her2-expressing tumors in clinics. Recently, we have shown that peptide nucleic acid (PNA)-mediated affibody-based pretargeted radionuclide therapy using beta-emitting radionuclide Lu-177 extended significantly survival of mice bearing human Her2-expressing tumor xenografts. In this study, we evaluated two approaches to use positron emission tomography (PET) for stratification of patients for affibody-based pretargeting therapy. The primary targeting probe Z(HER2:342)SR-HP1 and the secondary probe HP2 (both conjugated with DOTA chelator) were labeled with the positron-emitting radionuclide Ga. Biodistribution of both probes was measured in BALB/C nu/nu mice bearing either SKOV-3 xenografts with high Her2 expression or DU-145 xenografts with low Her2 expression. (68)GaHP2 was evaluated in the pretargeting setting. Tumor uptake of both probes was compared with the uptake of pretargeted Lu-177-HP2. The uptake of both Ga-68-Z(HER2:342)SR-HP1 and Ga-68-HP2 depended on Her2-expression level providing clear discrimination of between tumors with high and low Her2 expression. Tumor uptake of Ga-68-HP2 correlated better with the uptake of Lu-177-HP2 than the uptake of Ga-68 Z(HER2:342) SR-HP1. The use of Ga-68-HP2 as a theranostics counterpart would be preferable approach for clinical translation