Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / The use of direct seeding system brought changes on the weed management, by the mean of increasing of chemical control. The intense use of herbicides may have effect over the ecology of non-target soil organism. Two studies were conduct aiming testing the effect of herbicides over composition of soil mesofauna under genetically modified glyphosate resistance soy (RR®) (Chapter I) and assess the cito- genotoxicity effect of glyphosate, ammonium gluphosinate, paraquat and saflufenacil herbicide, applied during non-selective operation spray, before soy seeding (Chapter II). In Chapter I, results showed that in both agricultural years, soil mesofauna was dominate by Acari followed by Collembola, were Oribatida and Entomobryomorpha were the most predominating, respectively. In Chapter I, results showed of ammonium glufosinate favored an increase of springtails (Entomobryomorpha) and mites (Eupodes sp. Scheloribates sp. Galumnidae and Mesostigmata). Paraquat favored springtails (Entomobryomorpha) and mites (Pygmephoridae, Scheloribates sp. and Mesostigmata). Mite population (Pygmephoridae and Scheloribates sp.) increase with glyphosate treatment; and mites (Scheloribates sp.) with saflufenacil application; while in the glyphosate with saflufenacil association there was an increased springtails (Entomobryomorpha) density. The Haplotaxida Order show a greater sensitivity to glufosinato herbicides, paraquat and saflufenacil. In Chapter II, results showed that the glyphosate commercial formulation and analytical standard did not show cytotoxic effect at 5, 10 or 26ppm concentrations over the A. cepa cells; and only commercial formulation presented genotoxic. The gluphosinate shows no cytotoxic action, but tested plant cells, evidenced little genotoxic effect. Paraquat commercial formulation reduced cell division at the test concentrations (2, 4 and 11ppm) without genotoxic evidence. Saflufenacil did not affect cell division and express a weak genotoxicity using 0,25ppm concentration in plant cells test. / Com a introdução do sistema de plantio direto ocorreram mudanças no manejo de plantas daninhas, onde se intensificou o controle químico. O uso intenso de herbicidas pode ter efeito na ecologia de organismos não alvo presentes no solo. Nesse sentido foram conduzidos dois trabalhos objetivando avaliar o efeito de herbicidas sobre a composição da mesofauna edáfica em soja geneticamente modificada e resistência ao herbicida glifosato (soja RR®) (Capítulo I) e verificar o efeito citotóxico e de genotoxicidade de diferentes concentrações dos herbicidas glifosato, glufosinato, paraquat e saflufenacil, aplicados na operação de dessecação em pré-semeadura da soja RR® (Capítulo II). No capítulo I, os resultados mostraram que glufosinato favoreceu o aumento de colêmbolos (Entomobryomorpha) e ácaros (Eupodes sp. e Scheloribates sp. predadores Galumnidae e Mesostigmata). Paraquat favoreceu o aumento de colêmbolos (Entomobryomorpha) e ácaros (Pygmephoridae, Scheloribates sp. e Mesostigmata). A população dos ácaros (Pygmephoridae e Scheloribates sp.) aumentou com o tratamento glifosato; e dos ácaros (Scheloribates sp) com a aplicação de saflufenacil. Enquanto que na associação de glifosato com saflufenacil houve aumento da densidade de colêmbolos (Entomobryomorpha). A Ordem Haplotaxida apresentou maior sensibilidade aos herbicidas glufosinato, paraquat e saflufenacil. No capítulo II, os resultados mostraram que a formulação comercial e o padrão analítico do glifosato não apresentaram efeito citotóxico nas concentrações de 5, 10 ou 26ppm em células de Allium cepa; e apenas a formulação comercial apresentou ação genotóxica. O glufosinato não apresentou ação citotóxica, porém em células da planta teste se evidenciou pouca ação genotóxica. A formulação comercial de paraquat reduziu a divisão celular nas concentrações testadas (2, 4 e 11ppm), sem evidências de ação genotóxica. Saflufenacil não afetou a divisão celular e apresentou baixa ação genotóxica na concentração de 0,25ppm em células da planta teste.

La signalisation purinergique participe à de nombreux processus physiopathologiques dans le système cardiovasculaire. Alors que les nucléotides extracellulaires sont considérés comme des « signaux de danger » ; la NTPDase1(CD39), ectonucléotidase à l’origine de leur hydrolyse, permet de maintenir l’homéostasie vasculaire par ses actions anti-thrombotiques etimmuno-modulatrices. Le rôle de CD39 dans la fonction vasculaire liée à l’hypertension artérielle(HTA) reste méconnu. L’HTA, facteur de risque majeur de complications cardiovasculaires, est caractérisée par un remodelage structurel(hypertrophie, fibrose) et fonctionnel (hypercontractilité, dysfonction endothéliale) des vaisseaux, causées notamment par un stress oxydatif et une inflammation périvasculaire. L’objectif de notre projet a consisté à étudier l’évolution de CD39 ainsi que son rôle potentiel dans la condition vasculaire pathologique de l’HTA. Nous mettons en évidence une diminution de l’expression et de l’activité du CD39 vasculaire dans l’HTA. Une diminution de l’activité ADPase du CD39 soluble a également été observée au niveau circulant. L’étude des éléments à l’origine de cette diminution montre une sensibilité du transcrit vasculaire de CD39 à certaines cytokinespro- et anti-inflammatoires, mais également à une tension mécanique. Une étude in vivo du potentiel rôle de CD39 (souris déficientes pour le gène de CD39 (Entpd1) et traitement à l’apyrase) dans un modèle d’HTA à l’Angiotensine-II a également été réalisée. L’ensemble de ces données suggère qu’une diminution du CD39 vasculaire et circulant pourrait contribuer à majorer les altérations vasculaires contemporaines de l’HTA. / Purinergic signaling is involved in numerous physiopathological processes in cardiovascular system. While extracellular nucleotides are considered as « danger signals » ; the NTPDase1(CD39), ectonucleotidase responsible for their hydrolysis, preserves vascular homeostasis by itsanti-thrombotic and immunomodulatory actions.The role of CD39 in vascular function related to arterial hypertension remains unknown. Hypertension, the major risk factor of cardiovascular complications, is characterized by structural remodeling (hypertrophy, fibrosis) and functional (hypercontractility, endothelial dysfunction) of vessels caused in particular by perivascular oxidative stress and inflammation.Our aim was to investigate the evolution of CD39 expression / function and its potential contribution in the pathological vascular condition of hypertension. We highlighted a decrease invascular CD39 expression and activity in the context of hypertension. A decrease in soluble ADPase activity specific to CD39 was also observed in blood circulation. Investigation of elements responsible for this decrease reveals asensitivity of vascular CD39 transcription to several pro- and anti-inflammatory cytokines and to mechanical tension. In vivo study of potential role of CD39 (mice deficient for CD39 gene (Entpd1) and treatment with apyrase) in Angiotensin-II model of hypertension was also carried out. All these data suggest that a decrease in circulating and vascular CD39 may contribute to vascular changes associated with hypertension.

Les cellules cancéreuses sont capables de réactiver la transition Epithélio-Mésenchymateuse (EMT), mécanisme embryonnaire, pour acquérir une mobilité et une capacité de dédifférenciation. L'EMT conduit à une reprogrammation génétique avec la réactivation d'inducteurs de l'EMT, qui sont en majorité des facteurs de transcription (EMT-TF), et conduit à l'inhibition de miARN. Par ailleurs des stress oncogéniques sont essentiels à la progression tumorale. Le but de mon projet de thèse était de comprendre comment les événements de reprogrammation génétique survenant au cours de l'EMT coopèrent avec des stress oncogéniques dans la transformation tumorale mammaire.Premièrement, un criblage basé sur la coopération oncogénique en soft agar assay, entre les EMT-TFs et les stress oncogénique a été réalisé. Suite à une analyse bioinformatique, différentes signatures d'EMT-TF associés à un stress oncogénique ont été identifiées. Ainsi, par exemple, l'expression de l'EMT-TF Zeb1 et l'EMT-TF GSC sont associés à la délétion du gène suppresseur de tumeur PTEN pour transformer des cellules mammaires immortalisées. Une analyse en immuno-histochimie sur un set de 558 tumeurs du sein triple négatives a validé in vivo la présence d'une corrélation entre l'expression de GSC et l'expression de PTEN. Cependant cette association semble être plus complexe. En effet, l'expression de GSC est négativement associée à l'expression nucléaire de PTEN tandis qu'elle est positivement associée à l'expression de PTEN cytoplasmique. Enfin une analyse sur des métadonnées publiques de cancers telles que le TCGA ou le METABRIC est en cours pour valider ces signatures in vitro et plus largement pour déterminer comment l'EMT ou les signatures associées aux EMT-TF se corrèlent avec les voies oncogéniques classiques. Deuxièmement, une analyse in silico à partir d'algorithmes prédictifs de cibles de miARN, a été réalisée pour sélectionner les miARN capables d'inhiber l'expression de plusieurs EMT-TF. Deux miARN (miR-495 et 590-3p) ont été identifiés ciblant plusieurs membres des 4 principales familles d'EMT-TF (FoxC, Snail, bHLH et ZEB). Des tests in vitro ont été réalisés pour valider ces régulations identifiant Slug comme une cible de miR-590-3p. De plus, l'expression de ces miARN dans des lignées cellulaires mammaires est négativement associée à l'expression des EMT-TF et des marqueurs de l'EMT. Un traitement au TGF, inducteur de l'EMT, diminue leur expression, signifiant potentiellement que ces miARN peuvent négativement réguler l'EMT. En parallèle, plusieurs EMT-TF sont capables de réprimer l'expression de miR-590-3p, agissant directement sur son promoteur, créant ainsi des boucles de régulation. Des études fonctionnelles utilisant des vecteurs d'expression stable de miR-590-3p sembleraient montrer un rôle secondaire de ce miARN dans la régulation de l'EMT car mir-590-3p dérégule des marqueurs secondaires de l'EMT comme la N-cadhérine. Des études de restauration de fonctions sont envisagées pour déterminer quelle est l'importance de ces boucles de régulation dans la progression tumorale mammaire. Plus largement, l'expression des miARN identifiés va être corrélée avec les signatures associées aux EMT-TF et aux voies oncogéniques classiques pour déterminer le lien entre ces trois composants dans la tumorigenèse mammaire. Mes travaux de thèse ont montré qu'il existait un intéractome entre des inducteurs de l'EMT, des stress oncogéniques et des miARNs au cours de la transformation mammaire humaine / Cancer cells are able to reactivate the Epithelio-Mesenchymal Transition (EMT), an embryonic mechanism, to acquire mobility and dedifferentiation capacities. EMT leads to a genetic reprogramming with the reactivation of EMT inductors, mainly transcription factors (EMT-TF) and the inhibition of miRNA. Otherwise, oncogenic stresses are essentials to tumor progression. The aim of my thesis project was to have a better understanding about the cooperation between events of genetic reprogramming occurring during EMT and oncogenic stresses during mammary tumor transformation. First, a screening based on oncogenic cooperation in soft agar assay, between EMT-TFs and oncogenic stresses was performed. Following a bioinformatics analysis, different EMT-TFs signatures associated with an oncogenic stress were identified. Thus, for example, the expression of EMT-TF ZEB1 and GSC were associated with the deletion of tumor suppressor gene PTEN to transform immortalized mammary epithelial cells. An immunohistochemistry analysis on a set of 558 triple negative breast cancers validated in vivo the presence of a correlation between the expressions of GSC and PTEN. However, this association seems to be more complex. Indeed, the expression of GSC is negatively associated with the nuclear expression of PTEN while it’s positively associated with the cytoplasmic expression of PTEN. Finally, an analysis of public metadata on cancer samples as TCGA or METABRIC is ongoing to validate these in vitro signatures and wider to determine how EMT or EMT-TFs associated signatures correlate with classical oncogenic pathways.Secondly, an in silico analysis, from predictive algorithms of miRNA targets, was performed to select miRNA able to inhibit the expression of several EMT-TFs. Two miRNA (miR-495 and miR-590-3p) were identified targeting several members of four principal’s families of EMT-TFs (FOXC, Snail, bHLH and ZEB). In vitro tests were realized to validate these regulations identifying Slug as a target of miR-590-3p. Moreover, these miRNAs expression in mammary cell lines is negatively correlated with EMT-TFs expression and EMT markers. A treatment with TGF-, a major EMT inductor, decreases their expression, potentially meaning that these miRNA can negatively regulate EMT. In parallel, several EMT-TFs are able to repress the expression of miR-590-3p, acting directly on its promotor, thus creating feedback loops. Functional studies using stable expression vector of miR-590-3p suggest a secondary role of this miRNA in the regulation of EMT because miR-590-3p deregulates EMT secondary markers as N-Cadherin. Functions restauration studies are planned to determine how important these feedback loops in mammary tumor progression are. To open the project, expression of these identified miRNA will be correlated with EMT-TF associated signatures and with classical oncogenic pathways to determine the link between these three components in mammary tumorigenesis. My thesis works are shown that there is an interactome between EMT inductors, oncogenic stresses and miRNA during human mammary transformation

Les activités anthropiques liées à l'industrie nucléaire contribuent à des rejets continus de radionucléides dans les écosystèmes terrestres et aquatiques. Les travaux réalisés au cours de ce doctorat visent à apporter de nouvelles connaissances relatives aux effets des radiations ionisantes au cours d’une exposition multigénérationnelle de l’invertébré aquatique, Daphnia magna. Une irradiation gamma externe à des débits de doses pertinents du point de vue environnemental a été réalisée sur D. magna pendant trois générations successives. Les résultats mettent en évidence une accumulation et une transmission d’altérations de l’ADN au fil des générations, en parallèle d’une augmentation de la sensibilité des daphnies. Les données d’irradiation gamma et celles d’une étude antérieure de contamination alpha ont été analysées à l’aide du modèle mathématique DEBtox. Le modèle montre que les deux types de rayonnements agissent différemment sur les daphnies au cours des générations. Ce projet de recherche indique clairement qu’à l’avenir il est important d’étudier et de comprendre les effets transgénérationnels des radiations ionisantes à faibles doses. / Anthropogenic activities related to the nuclear industry contribute to continuous discharges of radionuclides into terrestrial and aquatic ecosystems. The aim of this PhD was to bring new knowledge on the effects of ionizing radiation during a multigenerational expose of the aquatic invertebrate, Daphnia magna. An external gamma radiation at environmentally relevant dose rates was performed on D. magna over three successive generations. Results show an accumulation and a transmission of DNA alterations over generations, in parallel of an increase in sensitivity of organisms. Gamma radiation data and those of a previous study of alpha contamination were analyzed using the mathematical model DEBtox. The model shows that the two types of radiation act differently on daphnia over generations. This research clearly indicates the importance of further studying and understanding transgenerational effects induced by low doses radiation in the future.

Les états septiques demeurent un réel problème de santé publique. Depuis 20 ans, leur mortalité est restée globalement constante en dépit d'une meilleure prise en charge initiale des patients et de nombreux essais cliniques. Parmi les défaillances d'organes provoquées par les états septiques, une profonde immunodépression se met en place après la phase initiale de la maladie. Son amplitude et sa persistance dans le temps, variables d'un patient à l'autre, semblent associées à un risque accru d'infections nosocomiales et de décès secondaire. Aussi, un des challenges actuels est d'explorer de nouvelles pistes thérapeutiques immunostimulantes pour les patients septiques les plus immunodéprimés. En l'absence de signe clinique de cet état, l'identification et la validation de nouveaux biomarqueurs contribuera sans doute à la mise en place de thérapies ciblées et individualisées. Notre travail s'inscrit dans ce contexte. L'objectif était d'utiliser le niveau d'expression génique comme outil de monitorage clinique et de recherche en physiopathologie. Nous avons donc conduit un travail de recherche translationnelle alliant études cliniques (lymphopénie, apoptose) et expérimentales basées sur un modèle de tolérance à l'endotoxine dans lequel nous avons testé différentes options thérapeutiques. Nous avons validé l'hypothèse de travail en montrant qu'un panel d'ARNm, mesurable dans le sang total des patients, devrait permettre à la fois d'identifier les patients qui pourraient bénéficier de thérapeutiques immunostimulantes et d'en contrôler l'efficacité dans la restauration des fonctions immunitaires / Septic syndromes remain a real public health issue. For 20 years, despite improvements in early management of patients and despite a number of clinical trials, the rate of mortality due to septic syndrome has remained broadly constant. After the initial phase of sepsis, patients rapidly exhibit profound immunodepression. Amplitude and duration of this state vary between patients and appear to be associated with increased risk of nosocomial infections and secondary deaths. One of the current challenges is to develop novel immunostimulant therapeutics for the most immunocompromised septic patients. Development of biomarkers will allow patient stratification and will undoubtedly contribute to the development of appropriately targeted and individualized therapies. The goal of our study was to evaluate the potential of gene expression level for clinical monitoring and for research in pathophysiology. We conducted translational research by combining experimental data with clinical studies (lymphopenia, apoptosis). We used endotoxin tolerance as a model to test different therapeutic options. Our data confirmed that expression levels of a panel of mRNAs, measured in the whole blood of patients, is a powerful tool for patient stratification and the monitoring of the effect of immunostimulant therapy on the immune system

This study is a symmetrical ethnography of the Czech development project Kola pro Afriku (Czech Bikes for Gambian Schools), which involves the collection, repairs, modification and shipment of old Czech bicycles to The Gambia. Once there, they are distributed to partner schools and offered to communing pupils. In my research, I mainly focus on the pivotal technology of the project, bicycles, and their performances. Drawing on classic ethnographies of development and (most importantly) on studies based on the actor-network theory (ANT), I gradually explore the bike collection process, their modifications and repairs, their shipment to The Gambia and their local operations. When doing so, I focus on the social topology of the bicycles and its transformations in the timespace. In this regard, the bicycles gradually appear as junk (i.e. a dysfunctional relict of stabilized networks), as a fluid collectivity and as individually fluid. Thereby, this study shows that technology transfers may lead not only to changes in the set of relations, of which the given object consists, but in the very modes, in which those relations arise. It is precisely these topological transformations that significantly contribute to the functioning of the project Kola pro Afriku. Key words: development cooperation,...

Introducción: Padecer sobrecarga del cuidador perjudica ampliamente la vida del cuidador. Sin embargo, su asociación con cuidar de adultos mayores con alteración neurológica no se encuentra muy estudiada. El objetivo del presente estudio es establecer la asociación entre cuidar adultos mayores con alteración neurológica y padecer sobrecarga del cuidador, en el Centro Geriátrico Naval del Perú, desde noviembre del 2019 a enero del 2021. Materiales y métodos: Estudio analítico, observacional, tipo transversal realizado en el Centro geriátrico del Centro Médico Naval. Se encuestaron 290 cuidadores que acudieron a consulta del adulto mayor cuidado. La sobrecarga del cuidador se midió con la escala de sobrecarga de Zarit. Resultados: Se halló una prevalencia de sobrecarga del cuidador de 52.76%. Los pacientes que padecían de alguna alteración neurológica fueron 62.76%. Al ajustar por las variables sociodemográficas, ser cónyuge del paciente aumentó en 2.23 veces la probabilidad de padecer sobrecarga del cuidador. Al ajustar por las variables relacionadas al cuidado, cuidar de un paciente con alteración neurológica y cuidar de un adulto mayor durante uno o dos años aumentaron en 1.86 y 1.91 veces, respectivamente, la probabilidad de padecer sobrecarga del cuidador, mientras que contar con el apoyo de otras personas disminuyó la probabilidad de padecerla en 39%. Conclusiones: La sobrecarga del cuidador se encuentra asociada con cuidar de un adulto mayor con alteración neurológica, ser cónyuge del paciente, realizar el cuidado durante uno o dos años y contar con apoyo de otras personas. / Introduction: Suffering caregiver burden greatly damages caregiver's life. However, its association with caring for older adults with neurological disorders is not well studied. The objective of this study is to establish the association between caring for older adults with neurological disorders and suffering from caregiver burden, at the Naval Geriatric Center of Peru, from November 2019 to January 2021. Materials and methods: Analytical, observational, cross-sectional study carried out at the Geriatric Center of the Naval Medical Center. A total of 290 older adult’s caregivers who went to medical consultation were surveyed. Caregiver burden was measured with the Zarit burden scale. Results: A prevalence of caregiver burden of 52.76% was found. The patients that suffered some neurological alteration were 62.76%. When adjusting for sociodemographic variables, being the patient's spouse increased the probability of suffering from caregiver burden by 2.23 times. When adjusting for the variables related to care, caring for a patient with neurological disorder and caring for an older adult for one or two years increased the probability of suffering caregiver burden by 1.86 and 1.91 times, respectively, while having the support of other people decreased the probability of suffering it by 39%. Conclusions: Caregiver overload is associated with caring for an older adult with neurological disorder, being the patient's spouse, caring for one or two years and having the support of other people. / Tesis

Purpose: Today two of the biggest problems within the construction industry in Sweden is the exceeding of budgets and that the projects do not finish in time. One of the reasons is the use of alterations, supplementary- and withdrawn work that occurs during the project. The purpose is therefore to study the variations that can be related to the documents that are used during public procurement as well as provide some suggestions on how the procurement documents can be improved for future projects. Hence trying to decrease the use of variations in projects. Method: The study consists of a multiple case study with three similar projects. The methods that are used are a literature study that provides the base of the intended study. A study of documents is also a crucial element to be able to draw the connections between the procurement documents and the alterations, supplementary- and withdrawn work. There will also be semi structured interviews that will strengthen the case study and increase the knowledge within the area. Findings: the study shows that 60 percent of the alterations, supplementary- and withdrawn work can be connected to the procurement documents. There are a few causes that leads to the use of alterations, supplementary- and withdrawn work in a project for example coordination between the different technical areas within the projects that can lead to contradictions in the documents. Too much material in the procurement documents can leads to conflicting information which leads to the use of alterations, supplementary- and withdrawn work. With greater accuracy and greater coordination between the different technical areas, drawings, and other documents. Coordination between the areas would also improve if it is implemented in the early stages of design. It is important to be clear in the technical description which work is expected from the project which would lead to fewer the alterations, supplementaryand withdrawn work. Implications: the overall problem is in this study is how you can reduce the use off alterations, supplementary- and withdrawn work connected to the procurement documents. Most of the alterations, supplementary- and withdrawn work in a project can be connected to these documents. To be able to reduce the cost there should be a system implemented regarding the review and coordination of the procurement documents. Limitations: This study is limited to three different projects from different municipalities, to secure a more certain result there should be more equivalent projects included in the study. The interviews are limited to the project managers that where responsible for the specific projects in this study. Keywords: alterations, supplementary- and withdrawn work, procurement documents, public procurement, specifications, regulations, technical specifications

Purpose: In today´s (2020) construction industry, partnering is mostly used in larger projects and municipalities. The purpose of this report is to study why partnering is not used to a greater extent in smaller municipalities. The goal of this report is to study whether smaller municipalities could benefit from applying partnering.    Method: To achieve the goal of this report, a case study was conducted with the data collection techniques interview and literature study. The interviews were conducted with three small municipalities, a large contractor and two municipal housing corporations. The literature study was done to attain an in-depth understanding of the concept of partnering and to investigate previous research on a similar topic.   Findings: The benefits of partnering are that the product will be good and the client get what they want as they are more involved in the project compared to regular procurement. The communication will be better and fewer disputes occur due to more frequent communication. Dedication and focus on the best of the projects are important elements for a succeeded partnering project. Partnering could be beneficial for a smaller municipality but the reason why partnering is not used to a greater extent in smaller municipalities is because it requires more time, energy, commitment and a big organisation. The municipalities also have concerns about projects being procured on a cost reimbursable contract.  Implications: The small municipalities could benefit from partnering but it should be applied on projects that are ongoing for a long time or when they do not know what they want. Those involved should spend a lot of time in the beginning of the project to decrease the costs. The municipalities should be dedicated in the project, cooperate with the contractors and put the best of the project in focus.   Limitations: The report´s limitations mean that the report is not applicable to major municipalities in Sweden. The tender stage and the economy are not included in the report. Alternative solutions to the problems with changes, additions and cancellations of jobs within construction law, apart from partnering, are not addressed. / Syfte: I dagens (2020) byggbransch används partnering mestadels i större projekt och i större kommuner, syftet med rapporten är att utreda varför partnering inte används mer i mindre kommuner.   Målet med rapporten är att studera ifall det kan gagna mindre kommuner att tillämpa partnering.      Metod:  För att uppnå målet har en fallstudie genomförts med datainsamlingsteknikerna intervju och litteraturstudie. Intervjuerna genomfördes med tre mindre kommuner, ett stort entreprenadföretag och två kommunala bostadsbolag. Litteraturstudien gjordes för att öka förståelsen för begreppet partnering och för att utreda vad tidigare forskning säger om ämnet.  Resultat: Fördelarna med partnering är att produkten blir bra och som verksamheten vill ha det, då de är mer involverade i projektet jämfört med traditionell upphandling. Kommunikationen blir bättre då de kommunicerar oftare och det uppstår färre tvister. Engagemang och att sätta projektet i fokus är viktiga beståndsdelar för ett lyckat partneringprojekt. Partnering kan vara gynnsamt för en mindre kommun om det tillämpas på rätt sätt. Anledningen till att inte partnering används mer i mindre kommuner är för att det kräver mer tid, pengar och engagemang samt en stor organisation från beställaren i partneringprojekten. Kommunerna har även en oro för löpande räkning där det inte är ett fast pris utan prissumman fastställs först när projektet är klart.    Konsekvenser: Det kan var gynnsamt att tillämpa partnering för mindre kommuner men det bör vara ett projekt som pågår under en längre tid eller det inte vet vad de vill ha. De involverade bör lägga ner mycket tid i början av projektet för att minska kostnaderna. Kommunerna bör vara engagerade i projektet, samarbeta med entreprenörerna och sätta projektets bästa i fokus.  Begränsningar: Rapportens begränsningar gör att resultatet ej är tillämpbar på större kommuner i Sverige. Anbudsskedet och ekonomin tas ej upp i rapporten. Alternativa lösningar på problemen med ÄTA-arbeten, förutom partnering, behandlas ej.

Pancreatic stellate cells (PSCs) constitute important cells of the pancreatic microenvironment and their close interaction with cancer cells is important in pancreatic cancer. It is currently not known whether PSCs accumulate genetic alterations that contribute to tumor biology. Our aim was to analyze genetic alterations in cancer associated PSCs. PSC DNA was matched to DNA isolated from pancreatic cancer patients’ blood (n = 5) and analyzed by Next-Generation Sequencing (NGS). Bioinformatic analysis was performed using the GATK software and pathogenicity prediction scores. Sanger sequencing was carried out to verify specific genetic alterations in a larger panel of PSCs (n = 50). NGS and GATK analysis identified on average 26 single nucleotide variants in PSC DNA as compared to the matched blood DNA that could be visualized with the Integrative Genomics Viewer. The absence of PDAC driver mutations (KRAS, p53, p16/INK4a, SMAD4) confirmed that PSC isolations were not contaminated with cancer cells. After filtering the variants, using different pathogenicity scores, ten genes were identified (SERPINB2, CNTNAP4, DENND4B, DPP4, FGFBP2, MIGA2, POLE, SNRNP40, TOP2B, and ZDHHC18) in single samples and confirmed by Sanger sequencing. As a proof of concept, functional analysis using control and SERPINB2 knock-out fibroblasts revealed functional effects on growth, migration, and collagen contraction. In conclusion, PSC DNA exhibit a substantial amount of single nucleotide variants that might have functional effects potentially contributing to tumor aggressiveness.