Tyrosine nitration results in altered function of smooth muscle voltage-gated L-type calcium channel. We explored the possibility that smooth muscle contains denitrase activity to allow functional recovery of the calcium channel without requiring synthesis of new channel proteins. Following peroxynitrite treatment of mouse colonic smooth muscle strips, CaCl2 (1 mM)-induced smooth muscle contraction was significantly reduced by 67% (P ≤ 0.05), which reversed by approximately 86% upon periodic washing within 2 hr period (P ≤ 0.001). The effect of the c-Src kinase inhibitor, PP2, on muscle contraction was also restored after 2 hr post-peroxynitrite treatment consistent with the thesis that recovery from tyrosine nitration allows for tyrosine phosphorylation of the calcium channel. In addition, sodium orthovanadate prevented nitration-induced inhibition of muscle contraction by approximately 90%. Moreover, denitration of nitrated proteins was observed by western blots in smooth muscle cells over 2 hr. Since nitrotyrosine formation interferes with tyrosine kinase pathways involved in cell signaling, the presence of denitrase activity in smooth muscle cells may have profound and important effects in restoring the function of nitrated proteins involved in cell signaling processes.

This thesis uses the methods of sychometrics and clinimetrics to develop and evaluate a Pediatric Ulcerative Colitis Activity Index (PUCAI). The initial phases of item generation and reduction were performed previously. This thesis comprises five main studies. Study one: the weighting and formatting of an initial draft PUCAI using a cohort of 157 children with ulcerative colitis, enrolled prospectively in five pediatric IBD centers. Study two: the validation of the final draft on a separate prospective cohort of 48 children undergoing complete colonoscopy. The PUCAI was highly correlated with physician global assessment (PGA) (r=0.91), Mayo score (r=0.95) and colonoscopic appearance (r=0.77). The PUCAI was able to differentiate the different categories of disease activity, and cutoff points were defined. Study three: Assessment of the responsiveness of the PUCAI. The index demonstrated excellent responsiveness on 75 children seen twice during the study period (effect size=1.9, standardized response mean=2.2, responsiveness statistics=2.6, correlation with PGA of change=0.84, and area under the ROC curve=0.97 95%CI 0.93- 0.99). Study four was aimed at evaluating the predictive validity of the PUCAI, on a retrospective cohort of 99 children with severe ulcerative colitis admitted for intravenous corticosteroid therapy. The PUCAI, calculated on the third and fifth day of therapy was highly predictive of therapy failure at discharge and one year post discharge (area under the ROC curve 0.84 (95%CI 0.76-0.92). Study five: a methodological study evaluating the preferred way to determine the minimal clinically important difference (MCID) of health-related outcome measures. This study was conducted using the PUCAI and three other well established instruments. It was concluded that the MCID should be determined primarily by the anchor-based approach using the ROC curve method on the entire cohort, supplemented by calculating the minimal detectable difference beyond statistical error using the standard error of measurement. Small, moderate and large MCID values could be presented based on the degree of expected relevant change. Together, these studies have contributed to the rigorous development and thorough evaluation of a novel, non-invasive tool for assessing disease activity in pediatric ulcerative colitis clinical studies and practice.

This thesis uses the methods of sychometrics and clinimetrics to develop and evaluate a Pediatric Ulcerative Colitis Activity Index (PUCAI). The initial phases of item generation and reduction were performed previously. This thesis comprises five main studies. Study one: the weighting and formatting of an initial draft PUCAI using a cohort of 157 children with ulcerative colitis, enrolled prospectively in five pediatric IBD centers. Study two: the validation of the final draft on a separate prospective cohort of 48 children undergoing complete colonoscopy. The PUCAI was highly correlated with physician global assessment (PGA) (r=0.91), Mayo score (r=0.95) and colonoscopic appearance (r=0.77). The PUCAI was able to differentiate the different categories of disease activity, and cutoff points were defined. Study three: Assessment of the responsiveness of the PUCAI. The index demonstrated excellent responsiveness on 75 children seen twice during the study period (effect size=1.9, standardized response mean=2.2, responsiveness statistics=2.6, correlation with PGA of change=0.84, and area under the ROC curve=0.97 95%CI 0.93- 0.99). Study four was aimed at evaluating the predictive validity of the PUCAI, on a retrospective cohort of 99 children with severe ulcerative colitis admitted for intravenous corticosteroid therapy. The PUCAI, calculated on the third and fifth day of therapy was highly predictive of therapy failure at discharge and one year post discharge (area under the ROC curve 0.84 (95%CI 0.76-0.92). Study five: a methodological study evaluating the preferred way to determine the minimal clinically important difference (MCID) of health-related outcome measures. This study was conducted using the PUCAI and three other well established instruments. It was concluded that the MCID should be determined primarily by the anchor-based approach using the ROC curve method on the entire cohort, supplemented by calculating the minimal detectable difference beyond statistical error using the standard error of measurement. Small, moderate and large MCID values could be presented based on the degree of expected relevant change. Together, these studies have contributed to the rigorous development and thorough evaluation of a novel, non-invasive tool for assessing disease activity in pediatric ulcerative colitis clinical studies and practice.

Tenocytes are the principal cells of the human Achilles tendon. In tendinosis, changes in the metabolism and morphology of these cells occur. Neurotrophins are growth factors essential for the development of the nervous system. Tumour necrosis factor alpha (TNF-α) has been found to kill sarcomas but has destructive effects in several major diseases. The two systems have interaction effects and are associated with apoptosis, proliferation, and pain signalling in various diseases. Whether these systems are present in the Achilles tendon and in Achilles tendinosis is unknown. The hypothesis is that the tenocytes produce substances belonging to these systems. In Studies I–III, we show that the potent effects of these substances are also likely to occur in the Achilles tendon. We found tenocyte immunoreactions for the neurotrophins brain-derived neurotrophic factor (BDNF), the nerve growth factor (NGF), the neurotrophin receptor p75, and for TNF-α and both of its receptors, TNFR1 and TNFR2. This occurred in both subjects with painful mid-portion Achilles tendinosis, and in controls. Furthermore, we found mRNA expression for BDNF and TNF-α in tenocytes, which proves that these cells produce these substances. TNFR1 mRNA was also detected for the tenocytes, and TNFR1 immunoreactions were upregulated in tendinosis tendons. This might explain why tenocytes in tendinosis undergo apoptosis more often than in normal tendons. Total physical activity (TPA) level and blood concentration of both soluble TNFR1 and BDNF were measured in Study IV. The results showed that the blood concentration of both factors were similar in subjects with tendinosis and in controls. Nevertheless, the TPA level was related to the blood concentration of sTNFR1 in tendinosis, but not in controls. This relationship should be studied further. The findings of this doctoral thesis show that neurotrophin and TNF-α systems are expressed in the Achilles tendon. We believe that the functions include tissue remodelling, proliferation and apoptosis.

The thesis titled The Physical activity in vegetarian women consists of two parts. The first, theoretical part is devoted mainly vegetarianism as such. There clarify the concept of vegetarianism, its distribution and nutritional aspects of a vegetarian diet with regular physical activity. Further topics are about physical activity recommendations for adults in the Czech Republic and in the global context. There are also benefits of human walk. The second part of the thesis deals with research of the issue. There is solved the question of vegetarianism and its potential impact on increasing the level of physical activity among women. To find answers was elected the research group of thirty vegetarian women and a control group of thirty women eating in the usual way in a similar age variance. Comparison of these two specific groups of women took place within the gained data from an international survey of PA IPAQ-long and weekly monitoring using pedometers six months in repetition. Based on the results wasn´t recorded demonstrable evidence that vegetarianism affecting the increase in the physical activity compared with the population eating in the conventional way.

No description available.

This doctoral dissertation reports on results from case studies of how text-talks in a Swedish upper secondary school vocational programme, function as a zone of proximal development for reading. The aim was to investigate how text-talks function as a basis for discussion about the text content and thereby have a potential for developing understanding for the subject-specific text content in the subjects of Carpentry Technology, Welding Technology and Swedish in one class in the first year of the Industrial Technology Programme. The study is qualitative with an explorative approach (Burns 2011). Ordinary teaching and learning contexts were observed. The theorectical frame work is based on sociocultural (Säljö 2000) and sociosemiotic perspectives (Halliday 1978), a hermeneutical frame consisting mainly of the concepts of the zone of proximal development (Vygotskij 1934/2001), scaffolding (Wood, Bruner &amp; Ross 1976), dialogicity (Bachtin 1986), and pedagogical codes (Bernstein 2000), as well as an analytical frame deriving from systemic-functional linguistics (Halliday &amp; Matthiessen 2004) and reception theory (Langer 1995, 2011a, 2011b). Three research questions were posed: How do the teachers organise and conduct the text-talks? What linguistic connections with the text are constructed when text content is introduced and developed in the text-talk? In what ways does movement in the text manifest in the text-talk? Data were collected through class-room observations and interviews. Field notes and recordings were made of eight text-talks, and three teacher interviews. Analyses of intertextual cohesion (Eggins 2004), and activity sequences (Martin &amp; Rose 2007) were conducted. Analyses of text-based, associative and interactive text-movability (Liberg et al. 2012b) show the collaborative meeting with the text as expressed in the text-talk. The results indicate that built-out cohesion and progressive text-movability can widen the discourse around the text and thereby scaffold reading development. / <p>Delfinansierat av Ovanåkers kommun.</p>

This doctoral dissertation reports on results from case studies of how text-talks in a Swedish upper secondary school vocational programme, function as a zone of proximal development for reading. The aim was to investigate how text-talks function as a basis for discussion about the text content and thereby have a potential for developing understanding for the subject-specific text content in the subjects of Carpentry Technology, Welding Technology and Swedish in one class in the first year of the Industrial Technology Programme. The study is qualitative with an explorative approach (Burns 2011). Ordinary teaching and learning contexts were observed. The theorectical frame work is based on sociocultural (Säljö 2000) and sociosemiotic perspectives (Halliday 1978), a hermeneutical frame consisting mainly of the concepts of the zone of proximal development (Vygotskij 1934/2001), scaffolding (Wood, Bruner &amp; Ross 1976), dialogicity (Bachtin 1986), and pedagogical codes (Bernstein 2000), as well as an analytical frame deriving from systemic-functional linguistics (Halliday &amp; Matthiessen 2004) and reception theory (Langer 1995, 2011a, 2011b). Three research questions were posed: How do the teachers organise and conduct the text-talks? What linguistic connections with the text are constructed when text content is introduced and developed in the text-talk? In what ways does movement in the text manifest in the text-talk? Data were collected through class-room observations and interviews. Field notes and recordings were made of eight text-talks, and three teacher interviews. Analyses of intertextual cohesion (Eggins 2004), and activity sequences (Martin &amp; Rose 2007) were conducted. Analyses of text-based, associative and interactive text-movability (Liberg et al. 2012b) show the collaborative meeting with the text as expressed in the text-talk. The results indicate that built-out cohesion and progressive text-movability can widen the discourse around the text and thereby scaffold reading development. / <p>Delfinansierat av Ovanåkers kommun.</p>

<p dir="ltr">Semiconductor technology has propelled human society into the information age, and that progress continues. Silicon CMOS device has been aggressively scaled down to 5 nm technology node. To further boost the on-state performance, MOS technology based on high-mobility channels such as III-V and Ge have been intensively studied. 3D structures such as FinFETs and gate-all-around (GAA) FETs are also applied to III-V and Ge to improve the electrostatic control of the channels for the ultimate scaling. </p><p><br></p><p dir="ltr">Traditional semiconductor device characterization techniques are inapplicable to devices created through these novel materials and device structures. This work applies various techniques to characterize a wide variety of semiconductor devices, in addition to presenting novel techniques studying the reliability of commercial off the shelf (COTS) products. Finally, the design of an ultra-low-power RF ASIC implementing wireless neural recording and stimulation, designed for cranial implantation, will be presented.</p>

<p>&nbsp;Upotrebom različitih ekstragenasa izvr&scaron;ena je ekstrakcija ploda, lista i korena belog (<em>Morus alba</em> L.) i crnog duda (<em>Morus nigra</em> L. ). Ekstrakcija etanolom je izvr&scaron;ena pri predhodno određenim optimalnim uslovima ekstrakcije (70% koncentracija etanola, temperatura 60&deg;C i odnos rastvarač:droga 20 ml/g). Ispitan je hemijski sastav ekstrakata različitih delova duda. Ispitivanja hemijskog sastava etanolnih ekstrakata obuhvatala su određivanje sadržaja ukupnih fenola, ukupnih flavonoida, ukupnih i monomernih antocijana, kvalitativni i kvantitativni sastav polifenolnih komponenata, kao i sadržaj mikro-, makro- i toksičnih elemenata. Najvedi sadržaj ukupnih fenolnih jedinjenja određen je u ekstraktu korena <em>M. nigra</em> (186 mg EHK/g), a najvedi sadržaj flavonoidnih jedinjenja u ekstraktu lista <em>M. nigra</em> (67 mg ER/g). U ekstraktima lista duda po svom sadržaju u odnosu na ukupan sadržaj polifenolnih jedinjenja ističe se kafena kiselina (od 53,34 do 62,11%), dok se u ekstraktima korena izdvaja hlorogenska kiselina (udeo vedi od 74%). U pogledu mineralnog sastava ekstrakata relativno veliki sadržaj Ca i Mg je karakterističan za obe vrste ekstrakata (vedi od 1.400 &mu;g/g). Mikroelementi u svim ispitanim uzorcima duda po opadajudem nivou, su Fe, B, Zn, Cu i Mn. U ekstraktima dobijenim superkritičnim CO₂određen je sadržaj masnih kiselina i ukupnih karotenoida. U ispitivanim ekstraktima dominante su nezasidene masne kiseline, linolna i linolenska kiselina, a značajan je udeo i zasidene masne kiseline (palmitinske kiseline).</p><p>Ispitivanje delovanja ekstrakata obuhvatalo je evaluaciju antioksidativne aktivnosti pradenjem sposobnosti neutralizacije slobodnih radikala, redukcionog potencijala i inhibicije lipidne peroksidacije. Po svim primenjenim metodama najvedu aktivnost je pokazao ekstrakt lista crnog duda. U zavr&scaron;noj fazi rada ispitana je in vitro citotoksična aktivnost ekstrakata duda, njihovim delovanjem na rast tri delijske linije: Hep2, RD i L2OB. Ekstrakti lista <em>M. nigra</em> su se pokazali kao najpotentniji inhibitori&nbsp;rasta na sve tri delijske linije (IC₅₀&lt;30 &mu;g/g). Na osnovu svih sprovedenih ispitivanja kao proizvod sa najboljim karakteristikama pokazao se ekstrakti lista <em>M. nigra</em>.</p> / <p>Using different extraction solvents extracts of fruit, leaves and roots of white (<em>Morus alba</em> L.) and black mulberry (<em>Morus nigra</em> L.) were prepared. Extraction by ethanol was carried out at the previously determined optimal extraction conditions (70% ethanol concentration, temperature 60&deg;C and the ratio of solvent: drug 20 ml/g). The chemical composition of extracts obtained from different parts of the mulberry were analysed. These analyses included the determination of total phenols, total flavonoids, monomeric and total anthocyanins, qualitative and quantitative composition of polyphenolic components, and the content of micro-, macro- and toxic elements. The highest phenolic content was determined in the extract of <em>M. nigra</em> root (186 mg ECA/ g), while the highest content of flavonoid compounds was determined in the extract of <em>M. nigra</em> leaves (67 mg ER/g). In the case of mulberry leaf extracts dominant phenolic compound, in relation to the total phenolic content, was caffeic acid (with contribution from 53.34 to 62.11%), while in the extracts of root extracts dominant phenolic compounds was chlorogenic acid (a higher proportion of 74%). In terms of mineral composition of the extracts relatively high content of Ca and Mg was characteristic of both types of extracts (greater than 1,400 mg/g). Measured content of trace elements in mulberry extracts decrease in the next order: Fe&gt; B&gt; Zn&gt; Cu&gt; Mn. In the extracts obtained by supercritical CO₂ fatty acids and total carotenoids were determined. In these extracts dominant unsaturated fatty acids were linoleic and linolenic acid. Also, significant proportion of saturated fatty acid (palmitic acid) has been detected.</p><p>Testing of extracts activity included the evaluation of antioxidant activity applying the methods based on: neutralize free radicals, reducing power potential and the inhibition of lipid peroxidation. All applied methods showed the highest activity of black mulberry leaf extract. In the final phase of work in vitro cytotoxic activity of mulberry extracts was examined. Their effect on growth of three cell lines: Hep2, RD, and L2OB were analysed. Extracts of <em>M. nigra</em> proved to be the most potent inhibitors of growth in all three cell lines (IC₅₀&lt;30 mg/g). On the basis of all conducted tests it has been proven that <em>M. nigra</em> extracts are products with the best characteristics.</p>