Convolutional Neural Networks and their Application in Cancer Diagnosis based on RNA-Sequencing

Η έκφραση γονιδίων αποτελεί τη μελέτη της λειτουργίας της γονιδιακής μεταγραφής, κατά την οποία συνθέτονται γονιδιακά προϊόντα, είδη RNA ή πρωτεΐνες. Η μελέτη της παρέχει την κατανόηση των κυτταρικών λειτουργιών, όπως η κυτταρική διαφοροποίηση και οι μη φυσιολογικές παθολογικές λειτουργίες. Ο καρκίνος αποτελεί μία γενετική ασθένεια όπου γενετικές παραλλαγές προκαλούν μη φυσιολογικές λειτουργίες στα γονίδια και τροποποιούν την έκφραση τους. Οι πρωτεΐνες, οι οποίες αποτελούν το τελικό αποτέλεσμα της έκφρασης γονιδίων, καθορίζουν τους φαινοτύπους και τις βιολογικές λειτουργίες. Συνεπώς, η ανίχνευση των επιπέδων έκφρασης γονιδίων δύναται να χρησιμοποιηθεί στη διάγνωση, την πρόγνωση, ακόμα και την επιλογή της θεραπείας του καρκίνου. Σε αυτή την πτυχιακή θα αναλυθεί η θεωρία και οι εφαρμογές της Βαθειάς Μάθησης. Στη συνέχεια, θα εφαρμοστεί η Βαθειά Μάθηση και πιο συγκεκριμένα ένα Συνελικτικό Νευρωνικό Δίκτυο, ως μέσο για τη διάγνωση πολλαπλών τύπων καρκίνου (κατηγοριοποίηση καρκίνων) χρησιμοποιώντας δεδομένα έκφρασης γονιδίων, και πιο συγκεκριμένα αλληλουχίες RNA. Τα δεδομένα του «The Cancer Genome Atlas» (TCGA) αποτελούνται από αλληλουχίες RNA. Θα επεξεργαστούν σε πρώτο επίπεδο και μετά θα μετατραπούν σε πολλαπλές δισδιάστατες εικόνες. Οι εικόνες αυτές θα εισαχθούν σε ένα Συνελικτικό Νευρωνικό Δίκτυο, το οποίο θα τις κατηγοριοποιήσει σε 33 τύπους καρκίνου, αποσκοπώντας στην διάγνωση με τη μέγιστη δυνατή ακρίβεια.Gene expression analysis is the study of the way genes are transcribed to synthesize functional gene products, functional RNA species, or protein products. Its study can provide insights of cellular processes, such as cellular differentiation and abnormal pathological processes. Cancer is a genetic disease where genetic variations cause abnormally functioning genes that appear to alter expression. Proteins, being the final products of gene expression, define the phenotypes and biological processes. Therefore, detecting gene expression levels can be used for cancer diagnosis, prognosis, and even treatment prediction. This thesis will be analyzing the theory and applications of Deep Learning. It will then apply Deep Learning (DL) and in particular a Convolutional Neural Network (CNN) as a means for the diagnosis of multiple cancer types (pan-cancer classification) using gene expression data and specifically RNA-sequencing. The Cancer Genome Atlas (TCGA) data, which consists of RNA-sequencing, will be preprocessed and then embedded into multiple two-dimensional (2D) images. These images will then be applied to a Convolutional Neural Network which will classify them into 33 types of cancer, in an attempt to achieve the highest possible diagnosis accuracy

Carbohydrate nanotubes production and its techno-economic validation

The production of carbohydrate nanotubes (CHNTs) using agricultural wastes is proposed in this investigation. The corncob was found to be the most productive for our purpose among the four lignocellulosic raw materials tested. CHNTs production was accomplished in two stages. Tubular cellulose (TC) was prepared from raw substrates through a delignification process, and the prepared tubes of TC were cut into nano-size carbohydrate tubes in a chemical-free process. To achieve this, cellulase was produced in our lab using agricultural residue, employing the non-pathogenic fungus Trichoderma reesei, a high cellulase producer. Analysis of the produced CHNTs proved stability, nano-dimension lengths, and increased crystallinity. The technoeconomic feasibility report showed that the production of CHNTs is cost-effective. This was supported by a process flow sheet with mass and energy balances based on laboratory experimental results

Technological Development of Brewing in Domestic Refrigerator Using Freeze-Dried Raw Materials

U radu je prikazan razvoj novog tipa piva za tržiste, koje se dobiva vrenjem pri niskoj temperaturi u hladnjaku s pomoću imobiliziranog kvasca. Zamrznuta sladovina te stanice soja kvasca Saccharomyces cerevisiae AXAZ-1, koji je otporan na smrzavanje, imobilizirane su na cijevnom modulu i zasebno upotrijebljene za vrenje pri niskim temperaturama (2, 5 i 7 °C). Ispitan je pozitivan učinak cijevnog modula na vrenje pri niskim temperaturama, te je utvrđeno da smrznute imobilizirane stanice kvasca na cijevnom modulu bitno smanjuju brzinu vrenja u usporedbi sa smrznutim slobodnim stanicama, koje su preporučene za proizvodnju piva kod kuće. Imobilizacija je također povećala otpornost kvasca na niske temperature vrenja, pa se najniža moguća temperatura vrenja spustila s 5 na 2 °C. Pri proizvodnji visokokvalitetnog piva ispitani su sljedeći parametri: utjecaj temperature i početne koncentracije šećera na kinetiku vrenja. Analizom gotovog proizvoda potvrđeno je poboljšanje senzorskih svojstava proizvedenog piva, s niskom koncentracijom diacetila, povećanim udjelom polifenola, te poboljšanim profilom arome i bistroćom. Predloženi postupak proizvodnje piva u hladnjaku može se lako komercijalizirati za kućnu uporabu otapanjem sadržaja dvaju pakiranja, jednog sa suhom sladovinom i drugog sa suhim stanicama kvasca imobiliziranim na cijevnom modulu i otopljenim u vodi.Development of a novel directly marketable beer brewed at low temperature in a domestic refrigerator combined with yeast immobilization technology is presented in this study. Separately, freeze-dried wort and immobilized cells of the cryotolerant yeast strain Saccharomyces cerevisiae AXAZ-1 on tubular cellulose were used in low-temperature fermentation (2, 5 and 7 °C). The positive effect of tubular cellulose during low-temperature brewing was examined, revealing that freeze-dried immobilized yeast cells on tubular cellulose significantly reduced the fermentation rates in contrast to freeze-dried free cells, although they are recommended for home-made beer production. Immobilization also enhanced the yeast resistance at low-temperature fermentation, reducing the minimum brewing temperature value from 5 to 2 °C. In the case of high-quality beer production, the effect of temperature and initial sugar concentration on the fermentation kinetics were assessed. Sensory enrichment of the produced beer was confirmed by the analysis of the final products, revealing a low diacetyl concentration, together with improved polyphenol content, aroma profile and clarity. The proposed process for beer production in a domestic refrigerator can easily be commercialized and applied by dissolving the content of two separate packages in tap water; one package containing dried wort and the other dried immobilized cells on tubular cellulose suspended in tap water

In vitro study on the cell adhesion ability of immobilized lactobacilli on natural supports

The aim of the present study was to investigate the effect of probiotic immobilization onto wheat grains, both wet and freeze dried, on the adhesion properties of the probiotic cells and make comparisons with wet and freeze dried free cells. Lactobacillus casei ATCC 393 and Lactobacillus plantarum NCIMB 8826 were used as model probiotic strains. The results showed satisfactory adhesion ability of free cells to a monolayer of Caco-2 cells (> 1000 CFU/100 Caco-2 cells for wet cells). Cell immobilization resulted in a significant decrease in adhesion, for both wet and freeze dried formulations, most likely because immobilized cells did not have direct access to the Caco-2 cells, but it still remained in adequate levels (> 100 CFU/100 Caco-2 cells for wet cells). No clear correlation could be observed between cell adhesion and the hydrophobicity of the bacterial cells, measured by the hexadecane adhesion assay. Most notably, immobilization enhanced the monolayer integrity of Caco-2 cells, demonstrated by a more than 2-fold increase in transepithelial electrical resistance (TEER) compared to free cells. SEM micrographs ascertained the adhesion of both immobilized and free cells to the brush border microvilli. Finally, the impact of the food matrix on the adhesion properties of probiotic bacteria and on the design of novel functional products is discussed

ACIDOGENIC FERMENTATION OF ALKALINE PRETREATED CORN STEM BIOMASS

Worldwide corn production is continuously increased in order to satisfy the growing demand for more food. However this leads to the production of a large amount of solid wastes that either left in the field or at best used as animal feed of low quality. In the present study a more sustainable exploitation of corn wastes (especially corn stem) was studied. Firstly corn stem biomass was effectively pretreated using NaOH solution, in order to improve its structure for the following acidogenic fermentation. The effect of alkaline pretreatment on biomass structure (using scanning electron microscopy and porosimetry) and on biomass lignin content was also evaluated. The anaerobic acidogenic fermentation experiments of the pretreated corn stem biomass were carried out using an up-flow anaerobic sludge blanket reactor (UASB) culture, either as free cells or immobilized on corn cob and kissiris. In all cases the immobilized cells increased the organic acids yields during the acidogenic fermentation. The main organic acids produced were lactic, acetic and butyric acid. The organic acids could be subsequently used either as chemicals or as substrate for the production of ester-based biofuels, as a cost-effective and environmentally friendly alternative for second generation biofuels production

Primjena kompozita s cjevastom celulozom u razvoju mesnih proizvoda s malim udjelom nitrita

Research background. Nitrite salts are among the most used preservatives in meat products as they ensure their safe consumption. Despite their positive effects on food safety and stability, many side effects on human health have been reported, leading to the need to reduce their use. Therefore, the aim of this study is to produce veal products with low nitrite content through low diffusion of potassium nitrite and to study their microbiological characteristics. Experimental approach. Edible tubular cellulose from leaf celery was produced and KNO2 was encapsulated in this material. This was achieved in two ways: by impregnation of tubular cellulose in a KNO2 solution under stirring and using starch gel as a stabilizer. Two samples of impregnated cellulose were applied on the surface of two veal samples of which one was stored at room temperature and the other at 3 °C. Similarly, two samples of cellulose with starch gel were applied on the surface of two veal samples of which one was stored at room temperature and the other at 3 °C. The KNO2 diffusion in different depths of the meat was measured and its effect on the microbiological characteristics of the meat was evaluated. Τhe experiment was carried out in duplicate. Results and conclusions. A satisfactory percentage of about 70 % of the initially encapsulated amount of KNO2 was diff. used in the meat, while the rest remained in the pores of the delignified leaf celery. The migrating amount of KNO2 proved to be effective in preserving meat, as the microbiological load decreased significantly (especially within the first 12 h, from a decrease of 0.6 log CFU/g up to 2.4 log CFU/g). Novelty and scientific contribution. The demand for meat products with low nitrite content is constantly increasing and the results of the present study are promising for the development of this technology in scale-up systems and on an industrial scale. This innovative approach could lead to products with controlled diffusion of the preservatives.Pozadina istraživanja. Nitriti su među najčešće korištenim konzervansima u mesnim proizvodima, jer osiguravaju njihovu sigurnu konzumaciju. Unatoč njihovom pozitivnom učinku na sigurnost i stabilnost hrane, zabilježene su mnoge štetne posljedice za ljudsko zdravlje, što je dovelo do potrebe za smanjenjem njihove uporabe. Stoga je svrha ovog istraživanja bila razviti proizvode od telećeg mesa s malim udjelom nitrita kao posljedicom slabe difuzije kalijevog nitrita, te proučiti njihove mikrobiološke značajke. Eksperimentalni pristup. U jestivoj cjevastoj celulozi proizvedenoj Iz lisnatog celera inkapsuliran je KNO2. To se postiglo na dva načina: impregnacijom cjevaste celuloze u otopini KNO2 uz miješanje, te uporabom škrobnog gela kao stabilizatora. Dva uzorka impregnirane celuloze nanesena su na površinu dvaju uzoraka teletine, od kojih je jedan čuvan na sobnoj temperaturi, a drugi na 3 °C. Slično tome, dva uzorka celuloze stabilizirane škrobnim gelom naneseni su na površinu dvaju uzoraka teletine, od kojih je jedan čuvan na sobnoj temperaturi, a drugi na 3 °C. Difuzija KNO2 mjerena je na različitim dubinama mesnog uzorka, te je procijenjen njezin učinak na mikrobiološka svojstva mesa. Ispitane su dvije serije uzoraka. Rezultati i zaključci. Zadovoljavajući postotak od oko 70 % početno inkapsulirane količine KNO2 difundirao je u meso, dok je ostatak zaostao u porama delignificiranog lista celera. Migrirajuća količina KNO2 pokazala se učinkovitom u očuvanju ispravnosti mesa, jer se mikrobiološko opterećenje bitno smanjilo (osobito unutar prvih 12 h, kad se smanjilo od 0,6 log CFU/g do 2,4 log CFU/g). Novina i znanstveni doprinos. Potražnja za mesnim proizvodima s malim udjelom nitrita u stalnom je porastu, a rezultati ovog rada su obećavajući za razvoj ove tehnologije u većim razmjerima te na industrijskoj razini. Ovaj inovativni pristup mogao bi dovesti do razvoja proizvoda u kojima je difuzija konzervansa pod kontrolom

Upgrading Brewer's Spent Grains by Treatment With Aspergillus Species

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