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Simple Summary CYCLON is a nuclear protein, which has been associated with disease progression and treatment resistance in DLBCL, the most common form of aggressive B-cell lymphoma, but also represents a predictive factor of refractory disease and relapse for immuno-chemotherapy-treated DLBCL patients. The molecular mechanisms related to this unstructured protein remain largely uncharacterized. Here, we performed a mass-spectrometry-based identification of the CYCLON protein interactome that suggested it could exert nucleolar functions related to cell proliferation. Among the CYCLON oncogenic network, we performed an immunohistochemical evaluation of the multi-functional nucleolar protein NPM1 in a DLBCL cohort and showed that CYCLON/NPM1 concomitant expression delineates a poor prognosis subgroup of patients. Multivariate survival analyses demonstrated that specific sub-cellular localizations of CYCLON and NPM1 represent independent novel predictors specifically associated with refractory DLBCL. Abstract R-CHOP immuno-chemotherapy significantly improved clinical management of diffuse large B-cell lymphoma (DLBCL). However, 30–40% of DLBCL patients still present a refractory disease or relapse. Most of the prognostic markers identified to date fail to accurately stratify high-risk DLBCL patients. We have previously shown that the nuclear protein CYCLON is associated with DLBCL disease progression and resistance to anti-CD20 immunotherapy in preclinical models. We also recently reported that it also represents a potent predictor of refractory disease and relapse in a retrospective DLBCL cohort. However, only sparse data are available to predict the potential biological role of CYCLON and how it might exert its adverse effects on lymphoma cells. Here, we characterized the protein interaction network of CYCLON, connecting this protein to the nucleolus, RNA processing, MYC signaling and cell cycle progression. Among this network, NPM1, a nucleolar multi-functional protein frequently deregulated in cancer, emerged as another potential target related to treatment resistance in DLBCL. Immunohistochemistry evaluation of CYCLON and NPM1 revealed that their co-expression is strongly related to inferior prognosis in DLBCL. More specifically, alternative sub-cellular localizations of the proteins (extra-nucleolar CYCLON and pan-cellular NPM1) represent independent predictive factors specifically associated to R-CHOP refractory DLBCL patients, which could allow them to be orientated towards risk-adapted or novel targeted therapies.

Diffuse Large B-Cell Lymphoma (DLBCL) is a clinically heterogeneous hematological cancer. Standard first line immunochemotherapy (R-CHOP) cure about 60% of fit patients. Despite extensive clinical, biological and molecular investigations, there is still no specific procedure to accurately discriminate refractory/relapse (R/R) DLBCL cases. On the one hand, overexpression of c-MYC or p53 is frequently found in DLBCL, but its association with prognosis remains controversial. On the other hand, CYCLON, a novel nuclear germline factor overexpressed in aggressive B-Cell Lymphoma, has been related to anti CD20 resistance in vitro. The aim of this study is to explore the expression of these biomarkers and their correlation with outcomes, clinical or pathological features. We established a retrospective cohort of 97 de novo DLBCL treated by R-CHOP. In univariate analysis, p53 overexpression (p53high) was associated with unfavorable outcomes and multivariate assessment showed that presence of a “starry-sky” pattern was correlated with better survival in p53high and/or c-MYC-positive DLBCL. NGS data revealed that these variables were associated with a specific mutational profile involved in cell survival. Atypical localizations of CYCLON and NPM1, an associated oncoprotein, were both strongly associated with progression free survival. Multivariate analyses showed that these atypical localizations of CYCLON and NPM1 were statistically significant and independent prognostic factors that add to the revised Index Prognosis (R-IPI) score for risk stratification by identifying DLBCL with especially worse prognosis. Altogether, we identified several potential druggable targets in DLBCL.; Le Lymphome B Diffus à Grandes Cellules (LBDGC) est un cancer très hétérogène, dont l’immunochimiothérapie de première ligne (R-CHOP) permet de traiter environ 60% des patients. Malgré les avancées cliniques, biologiques et moléculaires, il reste toujours difficile de prédire les LBDGC réfractaires ou chimio-résistants. La surexpression de c-MYC ou de p53, fréquemment retrouvée dans les LBDGC, a un impact pronostique encore incertain ; par ailleurs, CYCLON est une protéine surexprimée dans les lymphomes B agressifs en lien avec la résistance à l’anti CD20 in vitro. L’objectif de notre étude est de corréler l’expression de ces biomarqueurs avec la survie et les données clinico-pathologiques à partir d’une cohorte rétrospective de 97 LBDGC de novo traités par R-CHOP. Premièrement, les analyses statistiques ont montré que la surexpression de p53 (p53high) est associée à un mauvais pronostic. Il a été aussi mis en lumière le rôle protecteur, sur la survie, d’un aspect en « ciel étoilé » en cas de LBDGC p53high ou c-MYC positif. De plus, à partir des données NGS, ces trois variables ont pu être corrélées à un profil mutationnel spécifique en lien avec le renouvellement cellulaire. Indépendamment, nous avons montré que CYCLON et NPM1, protéine lui étant associée, sont en lien avec une survie diminuée en cas de localisations nucléaires atypiques. L’analyse multivariée a confirmé que ces dernières sont des facteurs pronostiques indépendants pouvant s’ajouter au score r-IPI (revised Index Prognosis) dans la stratification pronostique des LBDGC pour identifier ceux qui sont haut risque. Ainsi, nous avons identifié de nouvelles cibles thérapeutiques potentielles dans les LBDGC.

Обсяг пояснювальної записки до дипломного проекту складає 77 сторінок. Кількість ілюстрацій – 14, кількість таблиць – 12, кількість додатків – 7, кількість джерел згідно з переліком посилань – 27. Об’єктом дослідження є процес забруднення атмосферного повітря на підприємстві. Предмет дослідження – показники забруднення атмосферного повітря шкідливими речовинами. Метою даної роботи є пошук і визначення ефективних шляхів вдосконалення існуючої системи очистки атмосферного повітря на ПрАТ «Домобудівний комбінат No4» для зниження вмісту шкідливих речовин. Результати дослідження – модернізована схема очистки атмосферного повітря за допомогою наступного очисного обладнання: циклону СЦН - 40 900. Новизною являється вибір сучасного обладнання для очищення атмосферного повітря , що забезпечить зниження вмісту шкідливих речовин при викидах в атмосферу. Економічна ефективність – запропонована схема екологічно та економічно доцільна. Прогнозні припущення про розвиток об’єкту дослідження – вибрані та обгрунтовані параметр и обладнання для очищення атмосферного повітря. The volume of the diploma project`s explanatory note is 77 pages. Number of the illustrations - 14, number of the tables - 12, number of additions - 7, number of sources in accordance with the list of references - 27. The object of the research is the pollution of the atmospheric air. The subject of the research - indicators of the atmospheric air pollution by the harmful substances. The purpose of this work is to find and to determine effective ways to improve the existent atmospheric air cleaning system on PJSC "DSK - 4" to decrease the level of harmful substances. The results of the research is improved scheme of the atmospheric air cleaning system using the proposed cleaning equipment: СЦН - 40 900. The choose of the modern atmospheric air cleaning equipment is a novelty. This new equipment is going to decrease the level of harmful substances, emmitingin the atmosphere. Economic efficiency - the proposed scheme environmentally and economically feasible. Projected assumptions about the development of the researched object - are selected and grounded settings of atmospheric air cleaning equipment.

To eliminate particulate pollutants from air cyclones are being used. This article reviews the influence of particulate pollutants on cyclone insert. The stand was designed with possibility to change insert, rotation of engine and abrasive materials. Steel, stainless steel and polyurethane were used for inserts. Sand, glass balls, steel balls and corundum were used as abrasive materials. For the insert the steel balls has the strongest influence, when rotation of engine was 2400 rpm. Stainless steel was the most wearproof material for inserts. Santrauka Ciklonai naudojami dalelėms iš užteršto oro pašalinti. Šiame darbe buvo tirtas kietųjų dalelių poveikis vidinei ciklono sienelei. Suprojektuotas stendas, kuriame buvo galima keisti ciklono įdėklą, variklio sūkių dažnį ir abrazyvines medžiagas. Įdėklai pagaminti iš plieno, nerūdijančiojo plieno ir poliuretano. Kaip abrazyvinės medžiagos naudotas kvarcinis smėlis, stiklo rutuliukai, plieno rutuliukai ir korundas. Nustatyta, kad didžiausią poveikį sienelei daro plieno rutuliukai, kai variklio sūkių dažnis yra 2400 sūk./min, atspariausia dilimui medžiaga buvo nerūdijantysis plienas. Raktiniai žodžiai:abrazyvinės medžiagos, ciklonas, išdilimas, kietosios dalelės, nerūdijantysis plienas.

To eliminate particulate pollutants from air cyclones are being used. This article reviews the influence of particulate pollutants on cyclone insert. The stand was designed with possibility to change insert, rotation of engine and abrasive materials. Steel, stainless steel and polyurethane were used for inserts. Sand, glass balls, steel balls and corundum were used as abrasive materials. For the insert the steel balls has the strongest influence, when rotation of engine was 2400 rpm. Stainless steel was the most wearproof material for inserts. Article in Lithuanian. Skirtingų medžiagų ciklono darbinių paviršių dilimo, veikiant įvairioms abrazyvinėms medžiagoms, tyrimas Santrauka Ciklonai naudojami dalelėms iš užteršto oro pašalinti. Šiame darbe buvo tirtas kietųjų dalelių poveikis vidinei ciklono sienelei. Suprojektuotas stendas, kuriame buvo galima keisti ciklono įdėklą, variklio sūkių dažnį ir abrazyvines medžiagas. Įdėklai pagaminti iš plieno, nerūdijančiojo plieno ir poliuretano. Kaip abrazyvinės medžiagos naudotas kvarcinis smėlis, stiklo rutuliukai, plieno rutuliukai ir korundas. Nustatyta, kad didžiausią poveikį sienelei daro plieno rutuliukai, kai variklio sūkių dažnis yra 2400 sūk./min, atspariausia dilimui medžiaga buvo nerūdijantysis plienas. Raktiniai žodžiai:abrazyvinės medžiagos, ciklonas, išdilimas, kietosios dalelės, nerūdijantysis plienas.

In this article we analyze the variations of the Zenith Tropospheric Delay (ZTD) and its components, Zenith Hydrostatic Delay (ZHD) and Zenith Wet Delay (ZWD) recorded by the GPS reference stations in the area of the Canary Islands during the passing of the tropical storm Delta on November 28 and 29, 2005. During this event, we observed that all GPS stations experienced significant increases of the ZWD value of over 100 mm and a decrease in the ZHD values of about 30 mm. The increase of the normal ZWD values was detected several hours prior to the manifestation of the weather phenomena on the ground. We also noticed a connection between the maximum ZWD values observed and the temporal distribution of the rain. The observed variations of the tropospheric slant directional gradients correlate significantly with the variations in direction and intensity of the observed winds. The relation noted between the ZWD values and the tropospheric slant delay gradients with meteorological observables highlights the convenience of using existing or new GPS networks when studying weather phenomena such as severe cyclones.

L'objectiu principal del projecte és desenvolupar un simulador que permeti l'estudi de noves maneres de gestionar els recursos dins d'un cluster. Aquest simulador ha de ser tan fidel a la realitat com sigui possible. Per aquesta raó els paràmetres simulats seran els mínims imprescindibles per tal de donar la màxima credibilitat a les investigacions. Un dels objectius més importants que havia de complir el simulador era fer un ús real de la xarxa per totes les seves comunicacions. Un altre objectiu imprescindible és que el sistema ha de ser escalable per poder realitzar les investigacions que s'esperen poder realitzar amb ell. El primer objectiu a assolir és la investigació prèvia de les tecnologies i possibles solucions per realitzar el prototip. Serà la base en que es sustentarà el projecte i ens permetrà poder prendre decisions importants a l'hora de l'elecció de la tecnologia a usar. El simulador ens haurà de permetre simular un Clúster amb nombroses màquines i aplicacions en funcionament. El simulador realitzarà investigacions sobre la gestió de recursos per tal de millorar el rendiment global de les aplicacions. Cal destacar que aquest és un projecte obert. El que significa que no s'acaba en aquest PFC sinó que podrà ser mantingut en un futur, ampliat-lo per tal de millorar les investigacions. Un objectiu imprescindible és fer un disseny orientat a objectes, de fàcil modificació i comprensió per tal de facilitar futures versions.