Raskaan kaluston korjaamon layoutsuunnittelu

Opinnäytetyön aihe on raskaan kaluston korjaamon layoutsuunnittelu, joka tehtiin Raskone Oy:n Oulun korjaamolle. Työn tavoitteena oli uudistetun layoutin lisäksi parantaa korjaamotyön tuottavuutta. Korjaamon raskaan puolen tilojen supistaminen oli aiheuttanut ongelmia koko työvälinekannan säilytyksen ja käytettävyyden kanssa ja siksi layoutin uudistaminen oli ajankohtaista. Layoutin suunnittelussa hyödynnettiin perinteisen teollisuuden tuotannon kehitysmenetelmiä soveltamalla niitä korjaamoympäristöön. Käytettyjä tuotannon kehitysmenetelmiä olivat layoutsuunnittelu ja leaniin liittyvät laatutyökalut, kuten 5S ja arvovirtakuvaus. Työntekijät otettiin mukaan projektiin työryhmätoiminnalla. Työ alkoi tutustumalla yritykseen, sen toimintaan ja työn aiheeseen. Organisoitiin työryhmä, jonka kanssa käytiin läpi ongelmia aiheuttavia tekijöitä ja ratkaisuja. Suuri työvälinekanta ilman vakioituja säilytyspaikkoja supistetuissa työtiloissa oli suurin ongelma. Työryhmän kanssa kartoitettiin koko työvälinekanta, sen käyttökohteet ja käyttömäärät. Näiden tietojen pohjilta tehtiin inventaariolistaus, tuotekortit yksilöitävistä työvälineistä ja alkutilan kuvaus CAD-pohjapiirrokseen. Uuteen layoutiin suunniteltiin säilytyspaikat siirreltäville työvälineille huomioiden riippuvuussuhteet työkohteiden ja käyttömäärän mukaisesti. Uuden layoutin malli esiteltiin palaverissa, jossa esille tuli vielä uusia ideoita, jotka lisättiin ehdotuksen seuraavaan versioon. Viimeisin malli päätettiin ottaa käyttöön ja toteuttaa esitetyt muutokset tiloihin. Työn tuloksena oli uudistettu layout nykyisille tiloille ja työvälinekannalle. Uudistettu layout vähentää hukkaa eri työvälineitä käytettäessä, mikä mahdollistaa työn tuottavuuden paranemisen. Layoutin lisäksi syntyi paljon oheismateriaalia, kuten raskaan puolen työvälinekannasta tuore ja kattava inventaario, jota yritys voi hyödyntää toiminnassaan

Immunological Relevance of the Coevolution of IDO1 and AHR

The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor initially identified because of its role in controlling the cellular response to environmental molecules. More recently, AHR has been shown to play a crucial role in controlling innate and adaptive immune responses through several mechanisms, one of which is the regulation of tryptophan metabolism. Indoleamine-2,3-dioxygenase (IDO) and tryptophan-2,3-dioxygenase (TDO) are considered rate-limiting enzymes in the tryptophan catabolism and play important roles in the regulation of the immunity. Moreover, AHR and IDO/TDO are closely interconnected: AHR regulates IDO and TDO expression, and kynurenine produced by IDO/TDO is an AHR agonist. In this review, we propose to examine the relationship between AHR and IDO/TDO and its relevance for the regulation of the immune response in health and disease

ER stress and unfolded protein response in amyotrophic lateral sclerosis—a controversial role of protein disulphide isomerase

Accumulation of proteins in aberrant conformation occurs in many neurodegenerative diseases. Furthermore, dysfunctions in protein handling in endoplasmic reticulum (ER) and the following ER stress have been implicated in a vast number of diseases, such as amyotrophic lateral sclerosis (ALS). During excessive ER stress unfolded protein response (UPR) is activated to return ER to its normal physiological balance. The exact mechanisms of protein misfolding, accumulation and the following ER stress, which could lead to neurodegeneration, and the question whether UPR is a beneficial compensatory mechanism slowing down the neurodegenerative processes, are of interest. Protein disulphide isomerase (PDI) is a disulphide bond-modulating ER chaperone, which can also facilitate the ER-associated degradation (ERAD) of misfolded proteins. In this review we discuss the recent findings of ER stress, UPR and especially the role of PDI in ALS

CNS Redox Homeostasis and Dysfunction in Neurodegenerative Diseases

A single paragraph of about 200 words maximum. Neurodegenerative diseases (ND), such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis, pose a global challenge in the aging population due to the lack of treatments for their cure. Despite various disease-specific clinical symptoms, ND have some fundamental common pathological mechanisms involving oxidative stress and neuroinflammation. The present review focuses on the major causes of central nervous system (CNS) redox homeostasis imbalance comprising mitochondrial dysfunction and endoplasmic reticulum (ER) stress. Mitochondrial disturbances, leading to reduced mitochondrial function and elevated reactive oxygen species (ROS) production, are thought to be a major contributor to the pathogenesis of ND. ER dysfunction has been implicated in ND in which protein misfolding evidently causes ER stress. The consequences of ER stress ranges from an increase in ROS production to altered calcium efflux and proinflammatory signaling in glial cells. Both pathological pathways have links to ferroptotic cell death, which has been implicated to play an important role in ND. Pharmacological targeting of these pathological pathways may help alleviate or slow down neurodegeneration

Astrocyte alterations in neurodegenerative pathologies and their modeling in human induced pluripotent stem cell platforms

Astrocytes are the most abundant cell type in the brain. They were long considered only as passive support for neuronal cells. However, recent data have revealed many active roles for these cells both in maintenance of the normal physiological homeostasis in the brain as well as in neurodegeneration and disease. Moreover, human astrocytes have been found to be much more complex than their rodent counterparts, and to date, astrocytes are known to actively participate in a multitude of processes such as neurotransmitter uptake and recycling, gliotransmitter release, neuroenergetics, inflammation, modulation of synaptic activity, ionic balance, maintenance of the blood–brain barrier, and many other crucial functions of the brain. This review focuses on the role of astrocytes in human neurodegenerative disease and the potential of the novel stem cell-based platforms in modeling astrocytic functions in health and in disease.Peer reviewe

CNS Redox Homeostasis and Dysfunction in Neurodegenerative Diseases

A single paragraph of about 200 words maximum. Neurodegenerative diseases (ND), such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis, pose a global challenge in the aging population due to the lack of treatments for their cure. Despite various disease-specific clinical symptoms, ND have some fundamental common pathological mechanisms involving oxidative stress and neuroinflammation. The present review focuses on the major causes of central nervous system (CNS) redox homeostasis imbalance comprising mitochondrial dysfunction and endoplasmic reticulum (ER) stress. Mitochondrial disturbances, leading to reduced mitochondrial function and elevated reactive oxygen species (ROS) production, are thought to be a major contributor to the pathogenesis of ND. ER dysfunction has been implicated in ND in which protein misfolding evidently causes ER stress. The consequences of ER stress ranges from an increase in ROS production to altered calcium efflux and proinflammatory signaling in glial cells. Both pathological pathways have links to ferroptotic cell death, which has been implicated to play an important role in ND. Pharmacological targeting of these pathological pathways may help alleviate or slow down neurodegeneration

Development of a framework for radiographer online clinical education (FORCE): the specifc strand of nuclear medicine within this european project

The overall aim of the FORCE project is to develop virtual web-based learning resources where Radiography undergraduates can engage in interactive, problem-based development of radiographic knowledge, ability and professional awareness. This European-funded project is internally divided in three diferent strands (Radiology Diagnostic Imaging, Radiotherapy and Nuclear Medicine). The aim of this presentation is to present the global project, mainly focusing developments, achievements and challenges within the Nuclear Medicine specifc strand.info:eu-repo/semantics/publishedVersio

Granulocyte colony stimulating factor attenuates inflammation in a mouse model of amyotrophic lateral sclerosis

<p>Abstract</p> <p>Background</p> <p>Granulocyte colony stimulating factor (GCSF) is protective in animal models of various neurodegenerative diseases. We investigated whether pegfilgrastim, GCSF with sustained action, is protective in a mouse model of amyotrophic lateral sclerosis (ALS). ALS is a fatal neurodegenerative disease with manifestations of upper and lower motoneuron death and muscle atrophy accompanied by inflammation in the CNS and periphery.</p> <p>Methods</p> <p>Human mutant G93A superoxide dismutase (SOD1) ALS mice were treated with pegfilgrastim starting at the presymptomatic stage and continued until the end stage. After long-term pegfilgrastim treatment, the inflammation status was defined in the spinal cord and peripheral tissues including hematopoietic organs and muscle. The effect of GCSF on spinal cord neuron survival and microglia, bone marrow and spleen monocyte activation was assessed <it>in vitro</it>.</p> <p>Results</p> <p>Long-term pegfilgrastim treatment prolonged mutant SOD1 mice survival and attenuated both astro- and microgliosis in the spinal cord. Pegfilgrastim in SOD1 mice modulated the inflammatory cell populations in the bone marrow and spleen and reduced the production of pro-inflammatory cytokine in monocytes and microglia. The mobilization of hematopoietic stem cells into the circulation was restored back to basal level after long-term pegfilgrastim treatment in SOD1 mice while the storage of Ly6C expressing monocytes in the bone marrow and spleen remained elevated. After pegfilgrastim treatment, an increased proportion of these cells in the degenerative muscle was detected at the end stage of ALS.</p> <p>Conclusions</p> <p>GCSF attenuated inflammation in the CNS and the periphery in a mouse model of ALS and thereby delayed the progression of the disease. This mechanism of action targeting inflammation provides a new perspective of the usage of GCSF in the treatment of ALS.</p

System-wide Analysis of the T Cell Response

SummaryThe T cell receptor (TCR) controls the cellular adaptive immune response to antigens, but our understanding of TCR repertoire diversity and response to challenge is still incomplete. For example, TCR clones shared by different individuals with minimal alteration to germline gene sequences (public clones) are detectable in all vertebrates, but their significance is unknown. Although small in size, the zebrafish TCR repertoire is controlled by processes similar to those operating in mammals. Thus, we studied the zebrafish TCR repertoire and its response to stimulation with self and foreign antigens. We found that cross-reactive public TCRs dominate the T cell response, endowing a limited TCR repertoire with the ability to cope with diverse antigenic challenges. These features of vertebrate public TCRs might provide a mechanism for the rapid generation of protective T cell immunity, allowing a short temporal window for the development of more specific private T cell responses