Experimental Chemotherapy against Trypanosoma cruzi Infection Using Ruthenium Nitric Oxide Donors

The ruthenium NO donors of the group trans-[Ru(NO)(NH(3))(4)L](n+), where the ligand (L) is N-heterocyclic H(2)O, SO(3)(2 -), or triethyl phosphite, are able to lyse Trypanosoma cruzi in vitro and in vivo. Using half-maximal (50%) inhibitory concentrations against bloodstream trypomastigotes (IC(50)(try)) and cytotoxicity data on mammalian V-79 cells (IC(50)(V79)), the in vitro therapeutic indices (TIs) (IC(50)(V79)/IC(50)(try)) for these compounds were calculated. Compounds that exhibited an in vitro TI of >= 10 and trypanocidal activity against both epimastigotes and trypomastigotes with an IC(50)(try/epi) of <= 100 mu M were assayed in a mouse model for acute Chagas` disease, using two different routes (intraperitoneal and oral) for drug administration. A dose-effect relationship was observed, and from that, the ideal dose of 400 nmol/kg of body weight for both trans-[Ru(NO)(NH(3))(4)isn](BF(4))(3) (isn, isonicotinamide) and trans-[Ru(NO)(NH3) 4imN](BF4) 3 (imN, imidazole) and median (50%) effective doses (ED50) of 86 and 190 nmol/kg, respectively, were then calculated. Since the 50% lethal doses (LD(50)) for both compounds are higher than 125 mu mol/kg, the in vivo TIs (LD(50)/ED(50)) of the compounds are 1,453 for trans-[Ru(NO)(NH(3))(4)isn](BF(4))(3) and 658 for trans-[Ru(NO)(NH(3))(4)imN](BF(4))(3). Although these compounds exhibit a marked trypanocidal activity and are able to react with cysteine, they exhibit very low activity in T. cruzi -glycosomal glyceraldehyde-3-phosphate dehydrogenase tests, suggesting that this enzyme is not their target. The trans-[Ru(NO)(NH(3))(4)isn](BF(4))(3) and trans-[Ru(NO)(NH(3))(4)imN](BF(4))(3) compounds are able to eliminate amastigote nests in myocardium tissue at 400-nmol/kg doses and ensure the survival of all infected mice, thus opening a novel set of therapies to try against trypanosomatids.

Borgerlighetens ideal – arbetarnas verklighet. : En studie om Stora Tuna barnavårdsnämnds arbete 1903-1917.

Syftet med denna uppsats har varit att studera hur barnavårdsnämnden i Stora Tuna verkställde lagstiftningen om uppfostran åt vanartade och i sedligt avseende försummade barn. För att uppnå syftet med studien har barnavårdsnämndens ledamöter undersökts, lika så de anmälda barnen. Vad anmäldes de för, vilka blev konsekvenserna och vilka var det som stod för anmälningarna? Resultaten jämförs med tidigare forskning från andra platser. Huvudsakligen har protokoll från barnavårdsnämndens sammanträden mellan 1903 och 1917 använts för att besvara frågeställningarna.Resultatet visar att en klar majoritet av nämndens ledamöter representerade medelklassen eller överklassen, endast ett fåtal kom från arbetarklassen. Men de barn som anmäldes kom nästan uteslutande från arbetarklassen. Detta är något som den tidigare forskningen också framhåller. Pojkar anmäldes i betydligt högre utsträckning än flickor, men de flickor som anmäldes dömdes betydligt hårdare än pojkarna. Flickorna anmäldes främst på grund av de bristande hemförhållanden och påföljderna blev oftast att de skiljdes från hemmet till fosterhem eller till barnhem. Pojkarna anmäldes främst för stöld och den vanligaste påföljden blev en allvarlig varning. Polisen var den grupp som anmälde flest barn till nämnden.

Applicatiion of Almost ideal demand system for a pharmaceutical

This thesis is an application of the Almost Ideal Demand System approach of Deaton and Muellbauer,1980, for a particular pharmaceutical, Citalopram, in which GORMAN´s (1971) multi-stage budgeting approach is applied basically since it is one of the most useful approach in estimating demand for differentiated products. Citalopram is an antidepressant drug that is used in the treatment of major depression. As for most other pharmaceuticals whose the patent has expired, there exist branded and generic versions of Citalopram. This paper is aimed to define its demand system with two stage models for the branded version and five generic versions, and to show whether generic versions are able to compete with the branded version. I calculated the own price elasticities, and it made me possible to compare and make a conclusion about the consumers’ choices over the brand and generic drugs. Even though the models need for being developed with some additional variables, estimation results of models and uncompensated price elasticities indicated that the branded version has still power in the market, and generics are able to compete with lower prices. One important point that has to be taken into consideration is that the Swedish pharmaceutical market faced a reform on October 1, 2002, that aims to make consumer better informed about the price and decrease the overall expenditures for pharmaceuticals. Since there were not significantly enough generic sales to take into calculation before the reform, my paper covers sales after the reform.

Kön, kroppsbild och dysfunktionella tankar : en sambandsstudie

Body esteem is the affective aspect of body image, which is shaped by social experience. Compared with men, women have a more negative body image, which is more frequently correlated with depression and dysfunctional thoughts, especially in the case of eating disorders. The purpose of the present study was to examine gender differences in body esteem and its subcategories, and to find out whether there exists a stronger link between negative body esteem and higher levels of dysfunctional thoughts in women. The relationship between body esteem, dysfunctional thoughts and mental illness was examined. Participants were 73 college students doing social sciences and sports training educations. Body esteem questionnaire and dysfunctional thoughts questionnaire as well as a self made questionnaire on mental illness were used. Results showed that women had a more negative body esteem compared to men, especially considering weight. In women, there was a medium-strong negative relation between body esteem and dysfunctional thoughts. The results indicate that the norms for female body ideal that abound in the Western society have a negative affect on women's thinking and body image.Key words: Gender, body esteem, dysfunctional thoughts, mental illness.

Detecting Major Genes Controlling Robustness of Chicken Body Weight Using Double Generalized Linear Models

Detecting both the majors genes that control the phenotypic mean and those controlling phenotypic variance has been raised in quantitative trait loci analysis. In order to mapping both kinds of genes, we applied the idea of the classic Haley-Knott regression to double generalized linear models. We performed both kinds of quantitative trait loci detection for a Red Jungle Fowl x White Leghorn F2 intercross using double generalized linear models. It is shown that double generalized linear model is a proper and efficient approach for localizing variance-controlling genes. We compared two models with or without fixed sex effect and prefer including the sex effect in order to reduce the residual variances. We found that different genes might take effect on the body weight at different time as the chicken grows.

Minimization of stock weight during close-die forging of a spindle

In this paper, Finite Element method and full-scale experiments have been used to study a hot forging method for fabri-cation of a spindle using reduced initial stock size. The forging sequence is carried out in two stages. In the first stage, the hot rolled cylindrical billet is pre-formed and pierced in a closed die using a spherical nosed punch to within 20 mm of its base. This process of piercing or impact extrusion leads to high strains within the work piece but requires high press loads. In the second stage, the resulting cylinder is placed in a die with a flange chamber and upset forged to form a flange. The stock mass is optimized for complete die filling. Process parameters such as effective strain distribution, material flow and forging load in different stages of the process are analyzed. It is concluded from the simulations that minor modifications of piercing punch geometry to reduce contact between the punch and emerging vertical walls of the cylinder appreciably reduces the piercing load. In the flange chamber, a die surfaces angle of 52° instead of 45° is pro-posed to ensure effective material flow and exert sufficient tool pressure to achieve complete cavity filling. In order to achieve better compression, it is also proposed to shorten both the length of the inserted punch and the die “tongues” by a few mm.

Mastering : Undersökning av hur masteringsteknikers ideal och tidigare erfarenheter påverkar masteringsprocessen av inspelad musik

Genom att undersöka hur mycket av några masteringsteknikers personliga ideal och tidigare erfarenheter, med musikalisk bakgrund och smak, som hörs från masteringsprocesser av förelagda inspelningar av musik inom olika musikstilar är syftet att bidra med kunskap om hur mycket av de tidigare musikaliska influenserna en masteringstekniker tar med sig in i en masteringsprocess, och ses som användbar för fortsatt forskning inom ljud- och musikproduktion. Jag har låtit tre masteringstekniker under enskilda sessioner mastra tre ljudsekvenser, där jag även har observerat deras tillvägagångssätt, utfört intervjuer och sedan på egen hand granskat materialet genom att lyssna och titta på deras bearbetningar av ljuden. Slutligen har jag låtit fem vana lyssnare bedöma och kommentera mastringarna i form av en lyssningsundersökning. Utifrån observationerna, samtalen och min granskning tyder resultatet på att det personliga idealet och tidigare erfarenheten främst hörs i mastringar utförda av personer som är djupt rotade i sin favoritgenre och låter de idealen och arbetsmönstren även påverka mastringar inom främmande musikstilar.  

Genetic heterogeneity of within-family variance of body weight in Atlantic salmon (Salmo salar)

BACKGROUND: Canalization is defined as the stability of a genotype against minor variations in both environment and genetics. Genetic variation in degree of canalization causes heterogeneity of within-family variance. The aims of this study are twofold: (1) quantify genetic heterogeneity of (within-family) residual variance in Atlantic salmon and (2) test whether the observed heterogeneity of (within-family) residual variance can be explained by simple scaling effects. RESULTS: Analysis of body weight in Atlantic salmon using a double hierarchical generalized linear model (DHGLM) revealed substantial heterogeneity of within-family variance. The 95% prediction interval for within-family variance ranged from ~0.4 to 1.2 kg2, implying that the within-family variance of the most extreme high families is expected to be approximately three times larger than the extreme low families. For cross-sectional data, DHGLM with an animal mean sub-model resulted in severe bias, while a corresponding sire-dam model was appropriate. Heterogeneity of variance was not sensitive to Box-Cox transformations of phenotypes, which implies that heterogeneity of variance exists beyond what would be expected from simple scaling effects. CONCLUSIONS: Substantial heterogeneity of within-family variance was found for body weight in Atlantic salmon. A tendency towards higher variance with higher means (scaling effects) was observed, but heterogeneity of within-family variance existed beyond what could be explained by simple scaling effects. For cross-sectional data, using the animal mean sub-model in the DHGLM resulted in biased estimates of variance components, which differed substantially both from a standard linear mean animal model and a sire-dam DHGLM model. Although genetic differences in canalization were observed, selection for increased canalization is difficult, because there is limited individual information for the variance sub-model, especially when based on cross-sectional data. Furthermore, potential macro-environmental changes (diet, climatic region, etc.) may make genetic heterogeneity of variance a less stable trait over time and space.

Vilhelm Ekelund och den fransk-italienska kultursfären : Några nedslag i de tidiga prosaverken - från Antikt ideal (1909) till Attiskt i fågelperspektiv (1919)

Vilhelm Ekelund och den fransk-italienska kultursfären: Några nedslag i de tidiga prosaverken – från Antikt ideal (1909) till Attiskt i fågelperspektiv (1919). (Vilhelm Ekelund and the French and Italian cultural heritage: A study of his early prose – from Antikt ideal (1909) to Attiskt i fågelperspektiv (1919)). The Swedish poet, essayist and aphorist Vilhelm Ekelund was not only influenced by German literature and philosophy, he also wrote extensive literary criticism on the subject of Romance language authors. This article discusses Ekelund’s relationship to some of the most influential French and Italian writers – as it can be seen in his work during the period 1909-1919. This relationship was ambiguous: he paid homage to French authors such as Montaigne, Montesquieu, Stendhal and Comte – as well as to the Italian poet and philosopher Leopardi – but he also severely criticized such distinguished writers as Baudelaire, Rousseau and Maupassant. One conclusion of this article is that the authors praised by Ekelund all venerate the Greek and Roman cultural heritage, whereas the despised novelists and poets were, in his opinion, either too “modern” or too “feminine” – both highly pejorative adjectives in the author’s terminology. It is also noted that Ekelund’s most ferocious attacks date from the first part of the decade, before he entered a more harmonic period with the works Metron (1918) and Attiskt i fågelperspektiv (1919).

The relative perceptual weight of two Swedish prosodic contrasts

Abstract. In addition to 9 vowel and 18 consonant phonemes, Swedish has three prosodic phonemic contrasts: word stress, quantity and tonal word accent. There are also examples of distinctive phrase or sentence stress, where a verb can be followed by either an unstressed preposition or a stressed particle. This study focuses on word level and more specifically on word stress and tonal word accent in disyllabic words. When making curriculums for second language learners, teachers are helped by knowing which phonetic or phonological features are more or less crucial for the intelligibility of speech and there are some structural and anecdotal evidence that word stress should play a more important role for intelligibility of Swedish, than the tonal word accent. The Swedish word stress is about prominence contrasts between syllables, mainly signaled by syllable duration, while the tonal word accent is signaled mainly by pitch contour. The word stress contrast, as in armen [´arːmən] ‘the arm’ - armén [ar´meːn] ‘the army’, the first word trochaic and the second iambic, is present in all regional varieties of Swedish, and realized with roughly the same acoustic cues, while the tonal word accent, as in anden [´anːdən] ‘the duck’ - anden [`anːdən] ‘the spirit’ is absent in some dialects (as well as in singing), and also signaled with a variety of tonal patterns depending on region. The present study aims at comparing the respective perceptual weight of the two mentioned contrasts. Two lexical decision tests were carried out where in total 34 native Swedish listeners should decide whether a stimulus was a real word or a non-word. Real words of all mentioned categories were mixed with nonsense words and words that were mispronounced with opposite stress pattern or opposite tonal word accent category. The results show that distorted word stress caused more non-word judgments and more loss, than distorted word accent. Our conclusion is that intelligibility of Swedish is more sensitive to distorted word stress pattern than to distorted tonal word accent pattern. This is in compliance with the structural arguments presented above, and also with our own intuition.

DEN KOMMUNALA FÖRVALTNINGENSOM RATIONALISTISKT IDEAL- en fallstudie om styrning och handlingsutrymme inom skola,barnomsorg och miljö- och hälsoskydd

DEN KOMMUNALA FÖRVALTNINGEN SOM RATIONALISTISKT IDEAL - en fallstudie om styrning och handlingsutrymme inom skola, barnomsorg och miljö- och hälsoskydd.(The municipal authority as a rationalist ideal - a case-study on steering and scope for initiative within child-care, education and environmental departments.)A municipal authority is a considerable producer of services in the local community and iscommonly perceived as an important sector of the Swedish welfare system. One aspect of awell-functioning municipal organisation is that its administrative organs function efficiently.This study examines how activities in municipal administration are steered. The focus is on how different methods are used within a vertical hierarchical perspective to influence the actions of the participants and how the latter try to create space for action. To analyse the problem an ideal-type steering model is used.The study consists of three sections. In the first the research problem and the aims of the study are introduced as well as the methodological and theoretical approach. The result of the study is presented in the second section and in the third conclusions are drawn and discussed.The study shows that the perceptions of the participants involved regarding the possibilities of steering the everyday activities with the support of the methods studied differ on a number of points depending on the sector studied. When control of the various steering methods is distributed in different organisational units in the municipality a number of steering mechanisms operate side-by-side, sometimes in harmony and sometimes independently or in pure conflict with their goals. Steering leads to clear restrictions but there is clearlyroom for initiative, a ‘free-zone’ where the individual has room to act independently. Is it possible based on this study to state whether the ideal-type model functions in the way intended? On many accounts it would seem doubtful whether the effects of steering lead to beneficial effects for the activity. Rather it would seem that the effects of steeringsometimes function more or less randomly because the administration exists in a complexcontext in which the staff can be expected to have its own expectations and act in accordancewith them.

Role of dietary fats in modulating cardiometabolic risk during moderate weight gain : a randomized double-blind overfeeding trial (LIPOGAIN study)

BACKGROUND: Whether the type of dietary fat could alter cardiometabolic responses to a hypercaloric diet is unknown. In addition, subclinical cardiometabolic consequences of moderate weight gain require further study. METHODS AND RESULTS: In a 7-week, double-blind, parallel-group, randomized controlled trial, 39 healthy, lean individuals (mean age of 27±4) consumed muffins (51% of energy [%E] from fat and 44%E refined carbohydrates) providing 750 kcal/day added to their habitual diets. All muffins had identical contents, except for type of fat; sunflower oil rich in polyunsaturated fatty acids (PUFA diet) or palm oil rich in saturated fatty acids (SFA diet). Despite comparable weight gain in the 2 groups, total: high-density lipoprotein (HDL) cholesterol, low-density lipoprotein:HDL cholesterol, and apolipoprotein B:AI ratios decreased during the PUFA versus the SFA diet (-0.37±0.59 versus +0.07±0.29, -0.31±0.49 versus +0.05±0.28, and -0.07±0.11 versus +0.01±0.07, P=0.003, P=0.007, and P=0.01 for between-group differences), whereas no significant differences were observed for other cardiometabolic risk markers. In the whole group (ie, independently of fat type), body weight increased (+2.2%, P<0.001) together with increased plasma proinsulin (+21%, P=0.007), insulin (+17%, P=0.003), proprotein convertase subtilisin/kexin type 9, (+9%, P=0.008) fibroblast growth factor-21 (+31%, P=0.04), endothelial markers vascular cell adhesion molecule-1, intercellular adhesion molecule-1, and E-selectin (+9, +5, and +10%, respectively, P<0.01 for all), whereas nonesterified fatty acids decreased (-28%, P=0.001). CONCLUSIONS: Excess energy from PUFA versus SFA reduces atherogenic lipoproteins. Modest weight gain in young individuals induces hyperproinsulinemia and increases biomarkers of endothelial dysfunction, effects that may be partly outweighed by the lipid-lowering effects of PUFA. CLINICAL TRIAL REGISTRATION URL: http://ClinicalTrials.gov. Unique identifier: NCT01427140.