1,784 research outputs found
Hormonal treatments and the breast : effects on sex steroid receptor expression and proliferation
No full textBreast cancer is the most common malignancy among women in the western world. Hormonal treatments for contraception and replacement after menopause have been associated with an increased risk of breast cancer. The basis of risk associated with hormonal therapies may lie in the regulation of cell proliferation.Normal breast tissue samples from 27 women undergoing reduction mammoplasties were analysed for sex steroid receptor content and proliferation. Women using hormonal contraceptives displayed a higher proliferation rate (p=0.05) expressed as Ki-67/MIB-1 positivity than non-users. Proliferation displayed a strong positive correlation with IGF-I mRNA expression in breast tissue (rs =0.82, p=0.04). During treatment there was a down regulation of ER values.FNA biopsies were used to assess epithelial proliferation in normal breast tissue from 106 healthy premenopausal women with and without oral contraceptives. OC users had a higher (p=0.03) proliferation rate (mean 4.8 % of KI-67/MIB-1 positive cells) than non-users (mean 2.2 %). Increased proliferation was associated with reduced levels of circulating androgens and free testosterone (rs =- 0.38, pSurgically postmenopausal cynomolgus macaques were treated for 35 months with either CEE, MPA, CEE/MPA or tamoxifen. Proliferation in breast tissue was associated (p=0.016) with increased expression of p53. Tamoxifen was found to exert estrogen-like action in breast tissue by down-regulation of estrogen receptor expression and increased PRB levels. In the endometrium the lack of p53 expression in response to tamoxifen could be associated with an increased risk of endometrial cancer. Estrogen alone and estrogen in combination with progestogen was found to have different effects on the expression of sex steroid receptor isoforms in breast tissue. During combined CEE/MPA treatment both the ER-beta/ER-alpha and the PRA/PRB ratio had a tendency to be lower as compared to treatment with CEE alone. Suppression of the inhibitory isoforms ER-beta and PRA may relate to increased proliferation during combined estrogen/progestogen treatment.Ongoing HRT at the time of breast cancer diagnosis was found to influence certain tumor characteristics. Among 322 postmenopausal women with breast cancer 128 were using HRT at diagnosis. In this group the mean tissue concentrations of ER were lower (1.17 fmol/µg DNA) than in non-users (1.70 µg/DNA), pList of scientific papersI. Isaksson E, Sahlin L, Soderqvist G, von Schoultz E, Masironi B, Wickman M, Wilking N, von Schoultz B, Skoog L (1999). Expression of sex steroid receptors and IGF-1 mRNA in breast tissue--effects of hormonal treatment. J Steroid Biochem Mol Biol. 70(4-6): 257-62. https://pubmed.ncbi.nlm.nih.gov/10622416II. Isaksson E, von Schoultz E, Odlind V, Soderqvist G, Csemiczky G, Carlstrom K, Skoog L, von Schoultz B (2001). Effects of oral contraceptives on breast epithelial proliferation. Breast Cancer Res Treat. 65(2): 163-9. https://pubmed.ncbi.nlm.nih.gov/11261832III. Isaksson E, Cline JM, Skoog L, Soderqvist G, Wilking N, von Schoultz E, von Schoultz B (1999). p53 expression in breast and endometrium during estrogen and tamoxifen treatment of surgically postmenopausal cynomolgus macaques. Breast Cancer Res. Treat 53(1): 61-7. https://pubmed.ncbi.nlm.nih.gov/10206073IV. Isaksson E, Wang H, Sahlin L, von Schoultz B, Masironi B, von Schoultz E, Cline JM (2002). Expression of estrogen receptors (alpha, beta) and insulin-like growth factor-I in breast tissue from surgically postmenopausal cynomolgus macaques after long-term treatment with HRT and Tamoxifen. Breast.V. Isaksson E, Wang H, Sahlin L, von Schoultz B, Cline JM, von Schoultz E (2002). Effects of long-term HRT and Tamoxifen on the expression of progesterone receptors A and B in breast tissue from surgically postmenopausal cynomolgus macaques. [Submitted]VI. Isaksson E, Mahlman M, Nilsson B, Skoog L, Lofgren L, Wilking N, von Schoultz E (2002). Hormone replacement therapy and estrogen receptor expression in breast cancer. [Submitted]</p
Assessing the value of radical technology alternatives at system level
No full textThis study investigates the challenge to assess value when alternative technologies - of radical nature - are integrated on complex products. The study highlights three main challenges: 1) value depends on how the overall product platform is impacted over time 2) value depends on combination effects between technologies and 3) value depends on how the technology balances internal and external stakeholders needs simultaneously. The paper describes how these challenges can be tackled by novel modelling methods, illustrated with an example related to structural batteries
Pseudoconvex proximal splitting for L-infinity problems in multiview geometry
No full textIn this paper we study optimization methods for minimizing large-scale pseudoconvex L∞ problems in multiview geometry. We present a novel algorithm for solving this class of problem based on proximal splitting methods. We provide a brief derivation of the proposed method along with a general convergence analysis. The resulting meta-algorithm requires very little effort in terms of implementation and instead makes use of existing advanced solvers for non-linear optimization. Preliminary experiments on a number of real image datasets indicate that the proposed method experimentally matches or outperforms current state-of-the-art solvers for this class of problems
Dynamic lifecycle cost modeling for adaptable design optimization of additively remanufactured aeroengine components
No full textAdditive manufacturing (AM) is being used increasingly for repair and remanufacturing of aeroengine components. This enables the consideration of a design margin approach to satisfy changing requirements, in which component lifespan can be optimized for different lifecycle scenarios. This paradigm requires lifecycle cost (LCC) modeling; however, the LCC models available in the literature consider mostly the manufacturing of a component, not its repair or remanufacturing. There is thus a need for an LCC model that can consider AM for repair/remanufacturing to quantify corresponding costs and benefits. This paper presents a dynamic LCC model that estimates cumulative costs over the in-service phase and a nested design optimization problem formulation that determines the optimal component lifespan range to minimize overall cost while maximizing performance. The developed methodology is demonstrated by means of an aeroengine turbine rear structure
Jag skall bara… En kvalitativ studie om maskulinitet och risktagning på byggprogrammet.
No full textTitle: I'm just .. A qualitative study of masculinity and risk-taking on the construction program The purpose: The study aims to study the construction workers' training, i.e., the construction program and their internship. The focus of the study is masculinity perception and risktaking. Author: Beatrice Isaksson
Semester and year: SS 2014
Institution: Educational institution
Advisor: Abby Peterson Main findings: This article discusses the connection between hegemonic masculinity, risk-taking among young men heteronormativity and masculinity and health, in educational program for construction workers. The result shows that there is a hegemonian masculinity ideal in the educational program for construction workers that make the students more able to take risks
Keyword: Risk taking, Gender, Hegemoni masculinity, Health, Education, Construction Industr
Intrinsically Disordered Domains of the B Cell Receptor Cell-Free Expression and Characterization by NMR
No full textAfter the last twenty years of research, the occurrence of flexible proteins without a fixed three-dimensional structure are no longer considered to be rare exceptions from the structure-function paradigm. Instead, intrinsically disordered proteins (IDPs) have become one of the most interesting subjects of modern protein research. NMR is the best and most suitable technique for investigating the details of this protein class, and cell-free protein synthesis (CFPS) offers several advantages compared to conventional in vivo synthesis for the production of IDPs.
In this thesis, an integrated approach for efficient characterization of IDPs has been developed, combining CFPS and novel NMR methodology with fast spectroscopy and self-validating automatic assignment procedures. The technique has been demonstrated on disordered cytosolic domains of the B cell- and the T cell receptor. These domains are responsible for signal propagation into the immune cells, initiated by phosphorylation of tyrosines in their immunoreceptor tyrosine-based activation motifs (ITAMs). Secondary structure propensities have been observed and followed, going from a non-active form (non-phosphorylated) to an active form (phosphorylated) for the domains of the B cell receptor. A time-resolved technique for studying phosphorylation has also been developed and demonstrated on a B cell receptor domain.
Isotopic enrichment of amino acids is often a prerequisite for studying proteins with NMR, also representing the major cost of the CFPS system. A way to efficiently incorporate these labeled amino acids has therefore been investigated in this work.
CFPS does not only provide a unique technique for producing protease-sensitive IDPs, but also membrane proteins (MPs), inherently difficult to express in functional form. In this work it is demonstrated that CFPS can be successfully applied to express preparative amounts of co-solubilized MPs of varying size and complexities
Internkommunikation hos en mobiloperatör : – en studie av motivation och upptagningsförmåga av information hos butikschefer
No full textAbstract Title: Internal Communication at a large mobile operator (Internkommunikation hos en mobiloperatör - en studie av motivation och upptagningsförmåga av information hos butikschefer) Number of pages: 43 Author: Helena Isaksson Tutor: Peder Hård af Segerstad Course: Media and Communication Studies C Period: Fall term 2006 University: Division of Media and Communication, Department of Information Science, Uppsala University. Purpose/Aim: The purpose of this essay is to gain an insight in how a corporations store managers motivation affects the degree of information they absorb from information channels. Material/Method: The method that had been used in this essay is quantitative. It is based around a questionnaire aimed towards store managers and consequently used it to run regression analysis using the software package SPSS. Main results: The main result of the essay is that the motivation among store managers is positively related to the degree to which they absorb information. Thus, a possible problem exists for the corporation in that they need to make sure that the store managers are and stays motivated. Further, it seems that the longer a store manager has been employed by the corporation the less information is absorbed. The reader should although interpret the results with caution, since the limited sample could bias the estimates. Keywords: Internal communication, organizational communication, motivation, information, information channels and absorption of information
Insulin resistance in pancreatic cancer
No full textThe dismal prognosis of pancreatic cancer (PC) is related to metabolic complications of the tumor. Impaired glucose tolerance or diabetes due to insulin resistance, and cachexia are observed early and frequently in these patients. The basic mechanisms of PC-associated insulin resistance and weight loss are not fully understood. A majority of PC patients have obstructive jaundice and elevated plasma concentrations of islet amyloid polypeptide (IAPP), both of which may contribute to these metabolic alterations. Conditions associated with hyperinsulinemia are also of interest as a putative risk factors of PC, since insulin seems to promote carcinogenesis in the pancreas.To investigate the mechanisms of PC-associated insulin resistance, intact skeletal muscle of PC patients were incubated in vitro for assessment of glucose transport and insulin signaling through phosphatidylinositol (PI) 3-kinase. Glucose transporter (GLUT) 4, ATP, phosphocreatine, glycogen, and uncoupling protein (UCP) 2 and 3 mRNA and protein content were determined in other muscle biopsies. Patients with benign gastrointestinal diseases, chronic pancreatitis, and cancer of other sites were investigated as controls. GLUT4 transfected myoblasts were treated with media conditioned by PC cells and expression of UCPs monitored.To investigate metabolic effects of obstructive jaundice, bile duct ligated rats and sham-operated pair-fed and ad libitum fed controls were assessed for skeletal muscle glucose metabolism and UCP2 mRNA expression in muscle and liver. The effects of chronic IAPP exposure on the metabolism of glucose and other nutrients were determined in rats. A cohort of individuals of the Swedish Twin Registry was investigated for certain lifestyle factors and pancreatic cancer risk. Exposure data was obtained prospectively by questionnaires, and PC incidence was ascertained by linkage to the Swedish Cancer Registry.Twenty-six out of 30 PC patients had diabetes or impaired glucose tolerance. Insulin-stimulated glucose transport and PI 3-kinase activity were significantly decreased in skeletal muscle in these patients, but GLUT4 content was unchanged. Skeletal muscle insulin resistance was associated with increased expression of UCP2 and UCP3 and decreased ATP and glycogen content. These alterations were not found in patients with cancer of other sites or benign diseases who had a similar degree of weight loss. Conditioned media from PC cells increased the expression of UCPs in myoblasts.Obstructive jaundice and long term IAPP exposure did not result in skeletal muscle insulin resistance. Liver UCP2 expression was markedly upregulated and weight-loss was increased in jaundiced animals compared with pair-fed controls. Feeding was markedly reduced in IAPP-treated animals. Body weight gain was significantly reduced in IAPP-infused rats compared with pair-fed animals. In addition, IAPP-treated rats showed decreased intraabdominal fat mass. 176 cases of PC were found in the Swedish Twin Registry. Cigarette smoking, mild obesity, low physical activity, and high adult weight gain were all significant risk factors of PC.In conclusion, insulin resistance in PC patients includes impaired insulin signaling and glucose transport in skeletal muscle. This skeletal muscle metabolic alteration is associated with upregulation of UCP homologues, which may be triggered by PC cell-derived factor(s). Obstructive jaundice and IAPP exposure do not result in skeletal muscle insulin resistance, but are associated with metabolic alterations resulting in body weight loss. Lifestyle factors associated with peripheral insulin resistance increase the risk of PC development.List of scientific papersI. Isaksson B, Strommer L, Friess H, Buchler MW, Herrington MK, Wang F, Zierath JR, Wallberg-Henriksson H, Larsson J, Permert J (2003). Impaired insulin action on phosphatidylinositol 3-kinase activity and glucose transport in skeletal muscle of pancreatic cancer patients. Pancreas. 26(2): 173-7. https://pubmed.ncbi.nlm.nih.gov/12604916II. El-Ella GA, Isaksson B, Gasslander T, Permert J, Adrian TE (2003). Increased expression of uncoupling proteins 2 and 3 in insulin-resistant muscle from pancreatic cancer patients. [Submitted]III. Isaksson B, Rippe C, Simonoska R, Holm JE, Glaumann H, Segersvard R, Larsson J, Erlanson-Albertsson C, Permert J (2002). Obstructive jaundice results in increased liver expression of uncoupling protein 2 and intact skeletal muscle glucose metabolism in the rat. Scand J Gastroenterol. 37(1): 104-11. https://pubmed.ncbi.nlm.nih.gov/11843026IV. Isaksson B, Wang F, Permert J, Olsson M, Fruin B, Herrington MK, Enochsson L, Erlanson-Albertsson C, Arnelo U (2003). Chronically administrated islet amyloid polypeptide in rats serves as an adiposity inhibitor and regulates energy homeostasis. [Submitted]V. Isaksson B, Jonsson F, Pedersen NL, Larsson J, Feychting M, Permert J (2002). Lifestyle factors and pancreatic cancer risk: a cohort study from the Swedish Twin Registry. Int J Cancer. 98(3): 480-2. https://pubmed.ncbi.nlm.nih.gov/11920604</p
Påverkar revisionsbyråernas arbete med kompetensutveckling medarbetarnas resultat på revisorsexamen
No full textABSTRACT Titel: Påverkar revisionsbyråernas arbete med kompetensutveckling medarbetarnas resultat på revisorsexamen? Nivå: C-uppsats i företagsekonomi Författare: Gabriella Isaksson, Sofie Wallberg Handledare: Per-Arne Wikström Datum: 2013-03-21 Syfte: Syftet är att beskriva hur revisionsbyråerna kan arbeta med olika kompetensutvecklingsåtgärder för att få sina anställda att lyckas på revisorsexamen och därmed bli godkända revisorer. Metod: Vi studerade teorier om kompetensutveckling och undersökte hur revisionsbyråerna arbetade med olika kompetensutvecklingsåtgärder. Efter detta utvecklade vi en modell som var anpassad efter revisionsbyråernas arbete med kompetensutveckling. Vi genomförde sedan en enkätundersökning bestående av både öppna och slutna frågor med tentander från Big-4 byråer som skrivit revisorsexamen med godkänt resultat hösten 2011 eller våren 2012. Resultat & slutsats: Det visade sig att ett flertal kompetensutvecklingsfaktorer, bland annat utbildning och uppföljning, varit betydelsefulla för tentandernas prestation på revisorsexamen. Andra åtgärder, såsom utvecklingssamtal och mentorskap, var inte betydelsefulla för själva prestationen, utan hade större betydelse i andra sammanhang. Förslag till fortsatt forskning: Undersöka vilken påverkan kompetensutvecklingsåtgärderna har på prestationen "högre revisorsexamen". Uppsatsens bidrag: Studien bidrar till en ökad förståelse om vilken inverkan olika kompetensutvecklingsåtgärder har på prestationen på revisorsexamen och ger därmed revisionsbyråerna en möjlighet att genom planering hjälpa sina anställda till att nå ett godkänt resultat på revisorsexamen. Nyckelord: Kompetens, oberoende, kompetensutveckling, revisorsexamen, godkänd revisor.ABSTRACT Title: Does the auditor firms work with competence development affecton the employees results on auditor exam? Level: Final assignment for Bachelor's Degree in Business Administration Author: Gabriella Isaksson, Sofie Wallberg Supervisor: Per-Arne Wikström Date: 2013-03-21 Aim: The purpose is to describe how accountancy firms can work with competence development activities to make their employees to succeed on auditor examination and become approved auditors. Method: We studied the theories of competence development and examined how accounting firms work with competence development. We also developed a model tailored to their work and carried out a survey consisting of both openand closed questions to examinees from the Big-4 firms who wrote an accountant exam with passing grade during the autumn of 2011 or spring of 2012. Result & Conclusions: It turned out that a number of competence development factors, including education and monitoring, were significant for examinees performance on auditor examination. Other factors, such as performance reviews and coaching, was not significant for the performance but was more significant in other contexts. Suggestions for future research: Examine the impact of competence development for "higher auditor examination". Contribution of the thesis: This study contributes to a better understanding of the impact that the different competence development has on the performance of the auditor examination and gives accounting firms an opportunity and tools to help their employees to achieve a passing grade through planning. Key words: Competence, independence, competence development, auditor examination, approved auditor
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