Hematopoietic arginase 1 deficiency results in decreased leukocytosis and increased foam cell formation but does not affect atherosclerosis

Background and aimsArginase1 (Arg1), an M2 macrophage marker, plays a critical role in a number of immunological functions in macrophages, which are the main cell type facilitating atherosclerotic lesion development. Arg1 uses the substrate l-arginine to create l-ornithine, a precursor molecule required for collagen formation and vascular smooth muscle cell differentiation. By reducing l-arginine availability, Arg1 limits the production of nitric oxide (NO), a pro-atherogenic factor in macrophages. In endothelial cells, conversely, NO is strongly anti-atherogenic. However, until now, the role of Arg1 in atherosclerosis is largely unknown. The aim of this study is to specifically investigate the effect of Arg1 deletion in hematopoietic cells on atherosclerosis susceptibility.MethodsLdlr KO mice were transplanted with Arg1flox/flox;Tie2-Cre (Arg1 KO) bone marrow (BM) or wildtype (WT) BM. After 8 weeks of recovery on chow diet, recipients mice were fed a Western-Type Diet (WTD) for 10 weeks to induce atherosclerosis.ResultsAfter 10-week WTD challenge, blood leukocyte counts were decreased by 25% (p p = 0.05) in Ldlr KO mice transplanted with Arg1 KO BM compared to mice transplanted with WT BM. The decrease in leukocytes was due to lower B lymphocyte counts. However, oxLDL-specific antibodies were increased in plasma of Ldlr KO mice transplanted with Arg1 KO BM compared to WT BM transplanted controls, whereas oxLDL-specific IgM was not affected. On the other hand, peritoneal foam cells in Arg1 KO BM recipients were increased 3-fold (p ConclusionsDeletion of Arg1 in hematopoietic cells adversely affects blood leukocyte counts and increases foam cell formation. However, no effects on atherosclerosis could be demonstrated, indicating that hematopoietic Arg1 function is not a decisive factor in atherosclerotic plaque formation.Article / Letter to editorLeiden Academic Centre for Drug Researc

Hematopoietic arginase 1 deficiency results in decreased leukocytosis and increased foam cell formation but does not affect atherosclerosis

Background and aimsArginase1 (Arg1), an M2 macrophage marker, plays a critical role in a number of immunological functions in macrophages, which are the main cell type facilitating atherosclerotic lesion development. Arg1 uses the substrate l-arginine to create l-ornithine, a precursor molecule required for collagen formation and vascular smooth muscle cell differentiation. By reducing l-arginine availability, Arg1 limits the production of nitric oxide (NO), a pro-atherogenic factor in macrophages. In endothelial cells, conversely, NO is strongly anti-atherogenic. However, until now, the role of Arg1 in atherosclerosis is largely unknown. The aim of this study is to specifically investigate the effect of Arg1 deletion in hematopoietic cells on atherosclerosis susceptibility.MethodsLdlr KO mice were transplanted with Arg1flox/flox;Tie2-Cre (Arg1 KO) bone marrow (BM) or wildtype (WT) BM. After 8 weeks of recovery on chow diet, recipients mice were fed a Western-Type Diet (WTD) for 10 weeks to induce atherosclerosis.ResultsAfter 10-week WTD challenge, blood leukocyte counts were decreased by 25% (p p = 0.05) in Ldlr KO mice transplanted with Arg1 KO BM compared to mice transplanted with WT BM. The decrease in leukocytes was due to lower B lymphocyte counts. However, oxLDL-specific antibodies were increased in plasma of Ldlr KO mice transplanted with Arg1 KO BM compared to WT BM transplanted controls, whereas oxLDL-specific IgM was not affected. On the other hand, peritoneal foam cells in Arg1 KO BM recipients were increased 3-fold (p ConclusionsDeletion of Arg1 in hematopoietic cells adversely affects blood leukocyte counts and increases foam cell formation. However, no effects on atherosclerosis could be demonstrated, indicating that hematopoietic Arg1 function is not a decisive factor in atherosclerotic plaque formation.Article / Letter to editorLeiden Academic Centre for Drug Researc

Hematopoietic arginase 1 deficiency results in decreased leukocytosis and increased foam cell formation but does not affect atherosclerosis

Background and aimsArginase1 (Arg1), an M2 macrophage marker, plays a critical role in a number of immunological functions in macrophages, which are the main cell type facilitating atherosclerotic lesion development. Arg1 uses the substrate l-arginine to create l-ornithine, a precursor molecule required for collagen formation and vascular smooth muscle cell differentiation. By reducing l-arginine availability, Arg1 limits the production of nitric oxide (NO), a pro-atherogenic factor in macrophages. In endothelial cells, conversely, NO is strongly anti-atherogenic. However, until now, the role of Arg1 in atherosclerosis is largely unknown. The aim of this study is to specifically investigate the effect of Arg1 deletion in hematopoietic cells on atherosclerosis susceptibility.MethodsLdlr KO mice were transplanted with Arg1flox/flox;Tie2-Cre (Arg1 KO) bone marrow (BM) or wildtype (WT) BM. After 8 weeks of recovery on chow diet, recipients mice were fed a Western-Type Diet (WTD) for 10 weeks to induce atherosclerosis.ResultsAfter 10-week WTD challenge, blood leukocyte counts were decreased by 25% (p p = 0.05) in Ldlr KO mice transplanted with Arg1 KO BM compared to mice transplanted with WT BM. The decrease in leukocytes was due to lower B lymphocyte counts. However, oxLDL-specific antibodies were increased in plasma of Ldlr KO mice transplanted with Arg1 KO BM compared to WT BM transplanted controls, whereas oxLDL-specific IgM was not affected. On the other hand, peritoneal foam cells in Arg1 KO BM recipients were increased 3-fold (p ConclusionsDeletion of Arg1 in hematopoietic cells adversely affects blood leukocyte counts and increases foam cell formation. However, no effects on atherosclerosis could be demonstrated, indicating that hematopoietic Arg1 function is not a decisive factor in atherosclerotic plaque formation.Article / Letter to editorLeiden Academic Centre for Drug Researc

Hematopoietic arginase 1 deficiency results in decreased leukocytosis and increased foam cell formation but does not affect atherosclerosis

Background and aimsArginase1 (Arg1), an M2 macrophage marker, plays a critical role in a number of immunological functions in macrophages, which are the main cell type facilitating atherosclerotic lesion development. Arg1 uses the substrate l-arginine to create l-ornithine, a precursor molecule required for collagen formation and vascular smooth muscle cell differentiation. By reducing l-arginine availability, Arg1 limits the production of nitric oxide (NO), a pro-atherogenic factor in macrophages. In endothelial cells, conversely, NO is strongly anti-atherogenic. However, until now, the role of Arg1 in atherosclerosis is largely unknown. The aim of this study is to specifically investigate the effect of Arg1 deletion in hematopoietic cells on atherosclerosis susceptibility.MethodsLdlr KO mice were transplanted with Arg1flox/flox;Tie2-Cre (Arg1 KO) bone marrow (BM) or wildtype (WT) BM. After 8 weeks of recovery on chow diet, recipients mice were fed a Western-Type Diet (WTD) for 10 weeks to induce atherosclerosis.ResultsAfter 10-week WTD challenge, blood leukocyte counts were decreased by 25% (p p = 0.05) in Ldlr KO mice transplanted with Arg1 KO BM compared to mice transplanted with WT BM. The decrease in leukocytes was due to lower B lymphocyte counts. However, oxLDL-specific antibodies were increased in plasma of Ldlr KO mice transplanted with Arg1 KO BM compared to WT BM transplanted controls, whereas oxLDL-specific IgM was not affected. On the other hand, peritoneal foam cells in Arg1 KO BM recipients were increased 3-fold (p ConclusionsDeletion of Arg1 in hematopoietic cells adversely affects blood leukocyte counts and increases foam cell formation. However, no effects on atherosclerosis could be demonstrated, indicating that hematopoietic Arg1 function is not a decisive factor in atherosclerotic plaque formation.Article / Letter to editorLeiden Academic Centre for Drug Researc

Measurements, Algorithms, and Presentations of Reality: Framing Interactions with AI-Enabled Decision Support

Bringing AI technology into clinical practice has proved challenging for system designers and medical professionals alike. The academic literature has, for example, highlighted the dangers of black-box decision-making and biased datasets. Furthermore, end-users’ ability to validate a system’s performance often disappears following the introduction of AI decision-making. We present the MAP model to understand and describe the three stages through which medical observations are interpreted and handled by AI systems. These stages are Measurement, in which information is gathered and converted into data points that can be stored and processed; Algorithm, in which computational processes transform the collected data; and Presentation, where information is returned to the user for interpretation. For each stage, we highlight possible challenges that need to be overcome to develop Human-Centred AI systems. We illuminate our MAP model through complementary case studies on colonoscopy practice and dementia diagnosis, providing examples of the challenges encountered in real-world settings. By defining Human-AI interaction across these three stages, we untangle some of the inherent complexities in designing AI technology for clinical decision-making, and aim to overcome misalignment between medical end-users and AI researchers and developers

Toiminimen kirjanpito

Opinnäytetyön tavoitteena oli selvittää mitä osaamista tarvitaan toiminimen kirjanpidon toteuttamiseen. Työn toimeksiantajana toimi tamperelainen hyvinvointialan yrittäjä, joka ei ole toiminnastaan alv-velvollinen. Työn tarkoituksena oli kouluttaa tekijä peruskirjanpidon hoitamiseen. Tarkoituksena oli, että toimeksiantajan kirjanpito sekä veroilmoituksen täyttäminen ovat vuodesta 2017 eteenpäin opinnäytetyön tekijän vastuulla. Työn teoriaosuudessa keskityttiin kirjanpidollisiin peruskäsitteisiin toimeksiantajan elinkeinotoiminnan luonne huomioiden. Verotuksen osuudessa keskityttiin yritystulon verottamiseen yleensä ja esiteltiin ammatinharjoittajan veroilmoitus siltä osin, kun se toimeksiantajan yritystoiminta huomioiden oli tarpeellista. Sen lisäksi, että tekijä perehdytti itsensä alusta alkaen kirjanpidon maailmaan, teki työstä työlään erityisesti edellisvuosien kirjanpitomateriaaliin tutustuminen, sopivan kirjanpito-ohjelman etsiminen ja juoksevan kirjanpidon suorittaminen. Opinnäyteyön tavoite toteutui, sillä työn tekijällä on nyt tarvittava osaaminen kirjanpito-ohjelman käyttämiseen sekä juoksevan kirjanpidon hoitamiseen. Kirjanpidollisiin perusasioihin keskittyminen oli työn tavoitteen toteutumisen kannalta tärkeää, sillä perustietoja kirjanpidosta tekijällä ei juurikaan ennestään ollut. Toimeksiantajan kirjanpito on tällä hetkellä toteutettuna Tappio kirjanpito-ohjelmaa käyttäen elokuun 2017 loppuun asti. Opinnäytetyön liitteenä on Tappio-ohjelmasta poimitut tuloslaskelma ja tase. Kirjaukset perustavat tapahtumiin, jotka ovat muodostuneet 31.8.2017 mennessä. Opinnäytetyötä varten lukuja on muunnettu. Työ ei suinkaan lopu raportin palauttamiseen. Juoksevaa kirjanpitoa jatketaan loppuvuoden osalta ja tilinpäätös tulee toteuttaa vuoden 2018 alussa todellisia tilikauden lukuja käyttäen. Toimeksiantaja on myös ulkoistanut veroilmoituksen täyttämisen tämän työn tekijälle. Prosessin myötä tekijän osaaminen toiminimen kirjanpidon hoitamiseen on kohonnut ammattimaiselle tasolle, joten kirjanpitopalvelua voi jatkossa tarjota myös muille toiminimiyrittäjille. Tekijä jatkaa osaamisen kartoitusta tutustumalla alv-kirjauksiin.The purpose of this thesis was to find out what skills are required to perform the accounting for a sole trader. The commissioner was a welfare entrepreneur who practices business in Tampere. The business is not liable to pay value added tax. The aim of the thesis was to give the author the capability to perform the commissioner´s accounting independently in the future. The theoretical part of the thesis focused on the basic bookkeeping concepts considering the nature of the commissioner´s business. The taxation section focused on the business income, and the tax return was presented, as it is necessary for the commissioner´s business. An essential part of the work process was to familiarize with the accounting material of the previous years, to find a suitable accounting program, and to perform the current bookkeeping. The author is now capable of using the accounting program and keeping the accounts until preparing the income statement and balance sheet. Thus the goal of the thesis was reached. The routine bookkeeping continues and the financial statements will be prepared at the end of the year. The author will also complete the tax return for the financial year of 2017. Because of the professional development, the author can provide bookkeeping services to other welfare entrepreneurs, too

Why Do Employers (Fail to) Hire People with Disabilities? : A Systematic Review of Capabilities, Opportunities and Motivations.

Purpose To increase the number of people with disabilities in employment, we need to understand what influences employers’ hiring decisions. In this systematic review, we map out factors affecting employers’ hiring decisions about people with disabilities. Methods This study is a systematic review that applies the COM-B model to identify factors that contribute to employers (not) hiring people with disabilities. The COM-B model proposes that employers will perform hiring behavior (B) if they have the capability (C), opportunity (O) and motivation (M) to do so. We also investigate if factors have a negative, positive or no effect. We report in accordance with the PRISMA guidelines. Results In a review of 47 studies, we find 32 factors. Most of these factors are barriers. The most frequently mentioned barriers are employers’ (1) expectations that people with disabilities are unproductive, (2) expectations that people with disabilities cost a lot of money, and employers’ (3) lack of knowledge about disabilities. The most researched facilitators for employers to hire people with disabilities include (1) the motivation to help others, (2) working in a large organization, and (3) expecting a competitive advantage. The effect of factors can differ depending on contextual circumstances, including the type of organization, the type of disability and different policies. Conclusions We conclude that hiring decisions are influenced by an array of different barriers and facilitators. The effect of these factors can differ across organizations and disability types. Our study of factors affecting hiring can be used by scholars, policy makers, and organizations to create interventions to increase the hiring of people with disabilities

FUTURES-AMR: Towards an Adaptive Mesh Refinement Framework for Geosimulations

Adaptive Mesh Refinement (AMR) is a computational technique used to reduce the amount of computation and memory required in scientific simulations. Geosimulations are scientific simulations using geographic data, routinely used to predict outcomes of urbanization in urban studies. However, the lack of support for AMR techniques with geosimulations limits exploring prediction outcomes at multiple resolutions. In this paper, we propose an adaptive mesh refinement framework FUTURES-AMR, based on static user-defined policies to enable multi-resolution geosimulations. We develop a prototype for the cellular automaton based urban growth simulation FUTURES by exploiting static and dynamic mesh refinement techniques in conjunction with the Patch Growing Algorithm (PGA). While, the static refinement technique supports a statically defined fixed resolution mesh simulation at a location, the dynamic refinement technique supports dynamically refining the resolution based on simulation outcomes at runtime. Further, we develop two approaches - asynchronous AMR and synchronous AMR, suitable for parallel execution in a distributed computing environment with varying support for solution integration of the multi-resolution results. Finally, using the FUTURES-AMR framework with different policies in an urban study, we demonstrate reduced execution time, and low memory overhead for a multi-resolution simulation