<p>Cytokines play important roles in bone metabolism, participating in the complex interplay necessary for normal bone formation and turnover. The aim of the present thesis was to investigate the effects of two anti-inflammatory cytokines, interleukin-4 (IL-4) and interleukin-13 (IL-13) on bone. </p><p>Influence of pro- and anti-inflammatory cytokines on interleukin-6 (IL-6) formation in cultured human osteoblasts (hOBs) was investigated. IL-4 and IL-13 as well as interleukin-1 (IL-1) and tumour necrosis factor alpha and beta (TNF-α/β) stimulated IL-6 secretion in hOBs. Also, IL-4 and IL-13 synergistically potentiated the effect of IL-1 and TNFs on IL-6 secretion. </p><p>Effects of IL-4 and IL-13 on markers of osteoblastic activity in hOBs were investigated. IL-4 and IL-13 induced a dose-dependent increase in the formation of alkaline phosphatase (ALP) and pro-collagen type I carboxy-peptide (PICP) together with enhanced mineralization rate in hOBs. Formation of osteocalcin (OC) was unaffected. </p><p>The mechanism behind inhibited proliferation by IL-4 and IL-13 in hOBs was investigated. IL-4 and IL-13 caused a dose-dependent increase in DNA-fragmentation together with escalating Caspase-3 activity in hOBs, reflecting induced apoptosis. Osteoblast apoptosis was also confirmed by TNF-α, dexamethasone and by serum starvation.</p><p>The skeletal phenotype of IL-13^-/-, IL-4^-/-IL-13^-/- and WT mice was compared. An altered cortical bone mass was detected in adult male IL-4^-/-IL-13^-/- mice. They displayed a reduction in cortical bone mineral content (BMC) secondary to reduced cortical thickness. Mechanical strength of the cortical bone was reduced in level with the reduction detected in BMC. Trabecular bone mineral density (tvBMD) was unaffected. </p><p>Callus formation in IL-4^-/-IL-13^-/- and WT male mice was compared. No differences were found concerning radiological healing, biomechanical properties, callus parameters or histology. Heterotopic bone formation in IL-4^-/-IL-13^-/- and WT mice was compared using DXBM implants. No differences were found concerning mineralization of implants. Immuno-histology showed inhibition of autonomic nerves and lack of implant vascularization in IL-4^-/-IL-13^-/- mice. </p><p>In summery, the two anti-inflammatory cytokines IL-4 and IL-13 influence osteoblast activity and apoptosis <i>in vitro</i>. They also selectively influence cortical bone formation <i>in vivo</i>. These findings suggest a role for IL-4 and IL-13 in osteoblast differentiation, in bone metabolism and in bone formation. </p>

Cytokines play important roles in bone metabolism, participating in the complex interplay necessary for normal bone formation and turnover. The aim of the present thesis was to investigate the effects of two anti-inflammatory cytokines, interleukin-4 (IL-4) and interleukin-13 (IL-13) on bone. Influence of pro- and anti-inflammatory cytokines on interleukin-6 (IL-6) formation in cultured human osteoblasts (hOBs) was investigated. IL-4 and IL-13 as well as interleukin-1 (IL-1) and tumour necrosis factor alpha and beta (TNF-α/β) stimulated IL-6 secretion in hOBs. Also, IL-4 and IL-13 synergistically potentiated the effect of IL-1 and TNFs on IL-6 secretion. Effects of IL-4 and IL-13 on markers of osteoblastic activity in hOBs were investigated. IL-4 and IL-13 induced a dose-dependent increase in the formation of alkaline phosphatase (ALP) and pro-collagen type I carboxy-peptide (PICP) together with enhanced mineralization rate in hOBs. Formation of osteocalcin (OC) was unaffected. The mechanism behind inhibited proliferation by IL-4 and IL-13 in hOBs was investigated. IL-4 and IL-13 caused a dose-dependent increase in DNA-fragmentation together with escalating Caspase-3 activity in hOBs, reflecting induced apoptosis. Osteoblast apoptosis was also confirmed by TNF-α, dexamethasone and by serum starvation. The skeletal phenotype of IL-13-/-, IL-4-/-IL-13-/- and WT mice was compared. An altered cortical bone mass was detected in adult male IL-4-/-IL-13-/- mice. They displayed a reduction in cortical bone mineral content (BMC) secondary to reduced cortical thickness. Mechanical strength of the cortical bone was reduced in level with the reduction detected in BMC. Trabecular bone mineral density (tvBMD) was unaffected. Callus formation in IL-4-/-IL-13-/- and WT male mice was compared. No differences were found concerning radiological healing, biomechanical properties, callus parameters or histology. Heterotopic bone formation in IL-4-/-IL-13-/- and WT mice was compared using DXBM implants. No differences were found concerning mineralization of implants. Immuno-histology showed inhibition of autonomic nerves and lack of implant vascularization in IL-4-/-IL-13-/- mice. In summery, the two anti-inflammatory cytokines IL-4 and IL-13 influence osteoblast activity and apoptosis in vitro. They also selectively influence cortical bone formation in vivo. These findings suggest a role for IL-4 and IL-13 in osteoblast differentiation, in bone metabolism and in bone formation.

La valutazione del comportamento ambientale del metabolita di un pesticida è stato suddiviso in due studi indipendenti ma complementari tra loro utilizzando il metabolita radiomarcato con 14C: 1. Valutazione della degradazione aerobica del 14C-metabolita nel suolo; 2. Valutazione dell'assorbimento e desadsorbimento del 14C-metabolita nel suolo. L'attività di studio delle normative e dei regolamenti concernenti le Buone Pratiche di Laboratorio nell'ambito di studi multisito ed è poi sfociato nella gestione di uno studio di validazione di un metodo di analisi per la determinazione dei residui di glyphosate in frutta ed ortaggi. / The behaviour evaluation of a pesticide metabolite was divided in two different but complementary studies, using the radiolabeled metabolite: 1. evaluation of aerobic degradation of 14C-metabolite in soil; 2. evaluation of sorption of 14C-metabolite in soil. The study of GLP (Good Laboratory Practices) for multisite studies lead to the management of validation study for determination of glyphosate residues in fruits and vegetables.

Från den 1 januari 2013 är det obligatoriskt för börsnoterade företag som värderar sina tillgångar till verkligt värde att använda sig av IFRS 13. Tidigare studier angående hur organisationer anpassar sig till införandet av en ny redovisningsstandard är något som saknas. Detta trots att en sådan förändring är av betydelse för företagets ekonomistyrningssystem, vilket i sin tur är en viktig del av företagets organisation. Utifrån den tidiga institutionella teorin har denna studie sökt förklara hur organisationer anpassar sig till en ny redovisningsstandard med avseende på relationen mellan en extern redovisningsstandard och interna regler och rutiner. Studien har utförts genom att studera hur svenska fastighetsbolag har anpassat sig till införandet av IFRS 13, vilket har skett med hjälp av semistrukturerade intervjuer. Resultatet visade att externa resurser så som revisorer och branschpraxis, i form av vägledning vid implementering samt osäkerheter, hade en stor betydelse för företagens anpassning.

The purpose of this degree project was to examine which remedies are available to individuals when the State has violated their right to a fair trial as stated in article 6 in the European Convention on Human Rights. Furthermore, the aim was to, in cases where the remedy is determined to money, to clarify the indemnity rates that apply in determining the non-pecuniary damages. The starting point was a review of the European Court practice, domestic Swedish practice and relevant literature. The outcome of the review is that the remedies available to the individual’s disposal can be divided into two categories: primary and secondary remedies. Primary remedies mean compensation not consisting of money, and must be exhausted first. If the primary remedies are inadequate to compensate for the breach of the European Convention, a secondary remedy may be realised, i.e. pecuniary compensation. The primary remedies may include any legal measure, as long as it complies with the national traditions of the country and do not contradict the principle of legality. As for the non-pecuniary damage levels, it was found that the so-called Tariffs stated in the Zullo-case are not binding, but offer some guidance to be found from its flat rate. Each Convention State may decide upon the amount that it considers to be appropriate compensation for the Convention violations, as long as the levels are not significantly lower than what the European Court would decide.

The California experience previous to the passage of Proposition 13 taught the citizens of California that even with representation, the freedoms of individuals could be threatened. This lesson is especially true when we see the assessment scandals, a rapidly increasing real estate market and the failure of California’s representative officials to respond to the threat to individual liberty. In addition to watching corrupt tax assessors take advantage of the system, individuals were tired of paying inflated property taxes that were changing drastically from year to year. People’s homes were literally being taken from them by the power of the tax collector. This strongly deviated from the initial founding of our nation that was supposed to be “of the people, by the people and for the people.” While few people initially expected Proposition 13 to pass, ultimately it passed with 64.8 percent of the vote. The initiative process in California gave individuals the opportunity to make a constitutional amendment to the California Constitution in regards to the taxation processes of the government. With the passage of Proposition 13, the citizens of California made their statement.

El misterio de la creación (El Maase Bereshit) es uno de los dos temas más complejos del misticismo judío. Esta investigación se fundamenta en los procesos internos que el Ein Sof (el infinito) realiza con el objetivo de crear todo el universo. El estudio de la mística judía o cábala es un intento cosmológico, antropológico y psicológico de comprensión general de la realidad. La tesis doctoral presentada en la URV analiza el proceso de contracción de la divinidad, y las diversas manifestaciones divinas dentro de la creación. Se estudia en profundidad el Árbol de la Vida y sus diferentes dimensiones, ya que el Árbol de la Vida es una potente herramienta simbólica con la que los cabalistas trabajaron durante siglos para una mejor comprensión de la realidad. La mística judía también estudia las limitaciones del lenguaje para describir estos procesos tan amplios referentes a la creación del universo.

第22回名古屋大学年代測定総合研究センターシンポジウム平成21(2009)年度報告

ABSTRACT Endothelial dysfunction/apoptosis is critical to the development of neointima hyperplasia. Our pilot study identified a novel member of the caspase subfamily, caspase 13 (CASP 13), which is induced by oxidized low density lipoprotein (ox-LDL) in endothelial cells, but not in vascular smooth muscle cells. It remains controversial whether CASP 13 is a human or bovine gene. In this study, we collected four human brachial artery segments during arterioveinous fistula graft removal surgeries. By western blot and quantitative RT-PCR analysis, CASP13 expression was elevated at the anastomosis of brachial arteries from patients receiving hemodialysis. Rat carotid artery balloon model is widely used as in vivo atherosclerosis model for studies on neointima formation and especially vascular smooth muscle proliferation. However, most of the balloon injury studies terminated on the 14th day to sacrifice the animals for histological studies. In this study, we employed the ultrasonic device to record the hemodynamic changes in rat carotid artery at different time intervals after balloon injury. The pre-operative mean left carotid artery internal diameter and blood flow of Sprauge Dawley rats was 0.6 ¡Ó 0.07 mm and 28.75 ¡Ó 4.45 cm/sec, respectively. After balloon dilatation, the mean internal diameter of left carotid artery elevated to 0.77 ¡Ó 0.09 mm and 0.71 ¡Ó 0.08 mm on day 7 and day 14, respectively. Besides, the mean blood flow velocity also increased to 47.6 ¡Ó 9.2 cm/sec and 33.4 ¡Ó 10.8 cm/sec on day 7 and day 14, respectively. However, the left carotid artery blood flow velocity returned to 24 ¡Ó 3.5 cm/sec on day 21. The CASP 13 protein expression was found elevated in the balloon injury sites and mainly localized in the endothelial cells. In summary, CASP 13 is detected in endothelial cells in both human and rat atherosclerosis models and may constitute a novel molecular target for vascular diseases.

Zugl.: München, Univ., Diss., 2009