Tumor suppressor genes play a role as a growth regulator and a gatekeeper of a cell. Their inactivation is often detected in malignant tumors. Identification of novel tumor suppressor gene candidates may help to further understand tumorigenesis and aid in the discovery of a new treatment leading toward cure of cancer. This PhD research project aimed to understand functional significance of a novel tumor suppressor gene candidate, myosin IC (MYO1C) and to identify potential interaction(s) of the MYO1C protein with key components of the signaling pathways involving in cancer development. In an experimental rat model for endometrial carcinoma (EC), detailed molecular genetic analysis of a candidate tumor suppressor region located distal to the tumor protein 53 (Tp53) suggested the myosin IC gene (Myo1c) as the best potential target for deletion of the genetic material. The question arising was whether and how MYO1C could function as a tumor suppressor gene. By using qPCR, Western blot or immunohistochemistry analyses, we examined MYO1C protein level in panels of well-stratified human colorectal cancer (CRC) and EC respectively. We found that MYO1C was significantly down-regulated in these cancer materials and that for the EC panel, the observed down-regulation of MYO1C correlated with tumor stage, where tumors at more advanced stages had less expression of MYO1C. In cell transfection experiments, we found that over-expression of MYO1C significantly decreased cell proliferation, and silencing MYO1C with siRNA increased cell viability. Additionally, knockdown of MYO1C impaired the ability of cells to migrate, spread and adhere to the surface. Recent published studies suggested a potential interplay between MYO1C and the phosphoinositide 3-kinase (PI3K)/AKT pathway. To examine this hypothesis, we analyzed the expression and/or activation of components of the PI3K/AKT and RAS/ERK signaling pathways in vivo in CRC samples, and in vitro in cells transfected with the MYO1C gene expression construct or MYO1C-targeted siRNA. To identify other potential pathways/ mechanisms through which MYO1C may exert its tumor suppressor activity, we additionally performed new sets of MYO1C-siRNA knockdown experiments. At different time points post transfection, we performed microarray global gene expression experiments followed by bioinformatics analysis of the data. Altogether, the results suggested an early PI3K/AKT response to altered MYO1C expression. We additionally identified several cancer-related genes/pathways with late response to MYO1C knockdown. All things considered, the identification of MYO1C-expression impact on cell proliferation, migration, and adhesion in combination with its interplay between several cancer-related genes and signaling pathways provide further evidence for the initial hypothesis of a tumor suppressor activity of MYO1C. / Cellular, Molecular and Functional Characterization of the Tumor Suppressor Candidate MYO1C

Star formation occurs when the gas (mostly atomic hydrogen; H I) in a galaxy becomes disturbed, forming regions of high density gas, which then collapses to form stars. In dwarf galaxies it is still uncertain which processes contribute to star formation and how much they contribute to star formation. Blue compact dwarf (BCD) galaxies are low mass, low shear, gas rich galaxies that have high star formation rates when compared to other dwarf galaxies. What triggers the dense burst of star formation in BCDs but not other dwarfs is not well understood. It is often suggested that BCDs may have their starburst triggered by gravitational interactions with other galaxies, dwarf-dwarf galaxy mergers, or consumption of intergalactic gas. However, there are BCDs that appear isolated with respect to other galaxies, making an external disturbance unlikely. Here, I study six apparently isolated BCDs from the LITTLE THINGS1sample in an attempt to understand what has triggered their burst of star formation. LITTLE THINGS is an H I survey of 41 dwarf galaxies. Each galaxy has high angular and velocity resolution H I data from the Very Large Array (VLA) telescope and ancillary stellar data. I use these data to study the detailed morphology and kinematics of each galaxy, looking for signatures of starburst triggers. In addition to the VLA data, I have collected Green Bank Telescope data for the six BCDs. These high sensitivity, low resolution data are used to search the surrounding area of each galaxy for extended emission and possible nearby companion galaxies. The VLA data show evidence that each BCD has likely experienced some form of external disturbance despite their apparent isolation. These external disturbances potentially seen in the sample include: ongoing/advanced dwarf-dwarf mergers, an interaction with an unknown external object, and external gas consumption. The GBT data result in no nearby, separate H I companions at the sensitivity of the data. These data therefore suggest that even though these BCDs appear isolated, they have not been evolving in isolation. It is possible that these external disturbances may have triggered the starbursts that defines them as BCDs. 1Local Irregulars That Trace Luminosity Extremes, The H I Nearby Galaxy Survey; https://science.nrao.edu/science/surveys/littlethings

This doctoral thesis studies the properties and behaviour of phase-separated hydrogels. These can be prepared by interaction of polyelectrolytes with oppositely charged surfactants. Negatively charged polysaccharide hyaluronan and cationic surfactant carbethopendecinium bromide (Septonex), whose properties, behaviour and utilization are described in the first two chapters of theoretical part, were selected for this role. Hyaluronan is naturally-occuring in living organisms and is known for his specific targeting to the tumour cells. Septonex is used as antiseptic and disinfectant. Experimental part of this work is focused on examination of the structure and behaviour of these types of hydrogels especially from rheological point of view. The crucial part of this study was to establish mechanical properties and their dependence on environment. This led to design further studies. Structural analysis was held using the methods of ATR-FTIR, ionic chromatography and ICP-OES helping to measure the inner content of entry materials in the gels and supernatants respectively. The last chapter deals with antimicrobial activity. The results of this study indicate a potential usage of these substances in the field of medical applications.

The aim of this work was to study the influence of the pasteurization and filtration on selected chemical compounds in beer. Specifically, the influence on elemental composition, content of organic acids, carbohydrates and phenolic substances was studied. Optical emission spectrometry with inductively coupled plasma (ICP-OES) was used for elemental analysis of beer. Analysis of organic acids was evaluated by Ion chromatography. For analysis of carbohydrates was used High performance liquid chromatography with ELSD detector (HPLC-ELSD), phenolic compounds was evaluated by HPLC with diode array detector (HPLC-DAD). Data from analysis of beer was performed by usage of statistical methods (analysis of variance and principal component analysis). Parameters that showed the most significant differences between individual groups of beers were obtained. Correlations between the variables and the technological beer processing operations were found. 12 parameters of total 23 were affected. The effect of filtration and pasteurization was observed in content of the iron, silicon, potassium and magnesium, malate, monosaccharides glucose and fructose and phenolic compounds.

<p>Impulsni generator predstavlja jedan od najvažnijih delova bežičnog<br />primopredajnika. Pored toga što treba da generiše signal čiji<br />spektar zadovoljava odgovarajuću spektralnu masku, generator treba da<br />bude što jednostavniji, zauzima malu površinu i ima malu potrošnju.<br />Naučni doprinos ove doktorske disertacije predstavlja sedam novih<br />konfiguracija ultra-širokopojasnih impulsnih generatora<br />projektovanih u CMOS tehnologiji, od kojih su tri fabrikovane u<br />0,18 &mu;m UMC CMOS procesu. Prvi dizajn je zasnovan na principu<br />kombinovanja kratkotrajnih impulsa, sledeća tri sadrže ring<br />oscilator, naredna dva impulsna generatora koriste princip<br />filtriranja, dok poslednje novo rešenje obezbeđuje BPSK kodovanje<br />korišćenjem dva ring oscilatora.</p> / <p>Pulse generator is one of the most important parts of a wireless transceiver.<br />Besides generating a signal which spectrum has to satisfy corresponding<br />spectral mask, the pulse generator should have topology as simple as<br />possible, consume low power and occupy low die-area. Scientific contribution<br />of this dissertation are seven novel IR-UWB pulse generator architectures<br />designed in CMOS technology of which three are fabricated in 0.18 &mu;m UMC<br />CMOS process. The first design is based on combining very short pulses, the<br />next three contain a ring oscillator topology followed by two pulse generators<br />that use the filtering approach, while the last new solution enables BPSK<br />modulation by employing two ring oscillator topologies.</p>

<p>U doktorskoj disertaciji su prikazani elektronski sistemi razvijeni za<br />obradu signala sa senzora promenjive izlazne impedanse, koji se mogu<br />koristiti za različite vrste senzora. Razvijen je prototip mernog sistema<br />pomoću diskretnih komponenti. Merenja izvedena na ovom prototipu dokazala<br />su da se sa izabranom mernom metodom mogu dobiti zadovoljavajući rezultati<br />merenja. Projektovanjem analognog dela elektronskog sistema u CMOS<br />tehnologiji smanjene su dimenzije i potrošnja elektronskog sistema za obradu<br />signala, a poboljšane su merne karakteristike u odnosu na izvedu u<br />diskretnoj tehnologiji.</p> / <p>In this thesis, an electronic system for signal processing of sensors with variable<br />impedance has been developed. It can be used with different types of sensors. A<br />prototype of electronic system has been developed using discrete components.<br />Measurements made with this prototype have proved that applied measurement<br />method can be used to obtain satisfying measurement results. By designing analog<br />parts of electronic system in CMOS technology, dimensions and power consumption<br />of the electronic system for signal processing and measurement characteristics have<br />been improved, comparing to the prototype developed using discrete components.</p>

<p>U ovom radu kori&scaron;cen je spektroskopski, teorijski i hemometrijski pristup<br />proucavanju N-HO i N-H&middot;&middot;&middot; vodonicne veze koja se uspostavlja izmedu<br />amidnog protona i etarskog kiseonika tj aromaticnog sistema. U ovom radu<br />odredeni su parametri N-HO i N-H vodonicne veze za &scaron;esnaest Nsupstituisanih<br />amida sa tetrahidrofuranom i toluenom. Vecina ispitivanih amida do<br />sada nije bila izucavana sa stanovi&scaron;ta vodonicne veze. Uspostavljene su korelacije<br />izmedu spektorsopskih i teorijskih parametara. Izvr&scaron;eno je poredenje medu<br />osobinama vodonicno vezanih kompleksa za razlicite amide kao proton donore.<br />Svih 32 ispitivanih vodonicno vezanih kompleksa okarakterisano je<br />hemometrijskim metodama: Klaster analizom i analizom glavne komponente, na<br />osnovu spektroskopskih, teorijskih i Taftovih parametara</p> / <p> In this PhD thesis, N-H&times;&times;&times;O and N-H&middot;&middot;&middot; hydrogen bond beetwen the amide<br /> proton with ether oxygen and aromatic system has been investigated using the<br /> spectroscopic and theoretical approach. The study included sixteen N-substituted<br /> amides (formamides, acetamides, caproamides and benzamides) as well as<br /> tetrahydrofuran and toluene. The possibility of using chemometric methods was<br /> investigated in order to characterise N-H...O and N-H&middot;&middot;&middot; hydrgen bonded<br /> complexes. Hierarchial clustering and Principal Component Analysis (PCA) have<br /> been applied on infrared spectroscopic, PM3 theoretical and Taft parameters of 32 Nsubstituted<br /> amide complexes with tetrahydrofuran and toluene</p>

<p>U okviru doktorske disertacije opisane su jedinstvene fiziĉko-hemijske karakteristike<br />grupe supstanci benzena, toluena, etilbenzena i ksilena koje pripadaju istraživanjima<br />najnovijeg trenda nauĉne javnosti. Posebno su opisane perzistencija i<br />pseudoperzistencija, transport, distribucija i negativan i toksiĉan uticaj na zdravlje<br />ĉoveka i životnu sredinu. Sprovedena su eksperimentalna istraživanja zavisnosti<br />koncentracionih nivoa BTEX jedinjenja u izduvnim gasovima i operativnih parametara<br />eksperimentalnog motora SUS. Na osnovu dobijenih rezultata eksperimentalnih<br />istraživanja definisan je emisioni model BTEX jedinjenja simulacijom kretanja<br />putniĉkog automobila Fiat Punto Classic u skladu sa NEDC ciklusom koji na<br />odgovarajući naĉin reprezentuje standarde uslove vožnje u evropskim gradovima.</p> / <p>In this thesis, the unique physicochemical characteristics of a group of substances<br />consisting of benzene, toluene, ethylbenzene and xylene have been described.<br />Special emphasis has been placed on their characteristics of persistence and pseudopersistence,<br />transport, distribution and the negative and toxic influence on human<br />health and the environment. The experimental research of the interdependence of the<br />concentration levels of BTEX compounds in the exhaust gases and the operational<br />parameters of the experimental IC engine has been conducted. Based on the<br />experimental research results, the emission model of the BTEX compounds has been<br />defined by a simulation of movement of a Fiat Punto Classic passenger car in<br />accordance with the NEDC cycle, which appropriately represents the standard driving<br />conditions in European cities. Research conducted within the thesis represents the<br />newest trend of investigation in the scientific world.</p>

This thesis deals with turbulent mixing processes occuring in internal combustion engines, when applying exhaust gas recirculation (EGR). EGR is a very efficient way to reduce emissions of nitrogen oxides (NOx) in internal combustion engines. Exhaust gases are recirculated and mixed with the intake air of the engine, thus reducing the oxygen concentration of the combustion gas and the maximum combustion tempera- ture. This temperature decrease results in a reduction of NOx emissions, since NOx is produced at high temperatures.The issue of NOx reduction is of high importance for current engine development (particularly for heavy-duty engines), since NOx is the main cause for smog formation and subject to increasingly stronger emission legislation. One of the practical problems when applying EGR is the non-uniformity of the mixture among and inside the cylinders deteriorating the engine and emission performance.The aim of this work is to develop and assess methods suited for the computation of turbulent mixing processes in engine conditions. More specifically, RANS and LES computations are considered. The flow structures responsible for the mixing are analyzed for two different T-junctions and a six-cylinder Scania engine-manifold. Shortcomings and advantages of the applied mixing models are explained.The main results are, that commonly applied scalar flux models for the RANS framework do not predict correct scalar flux directions. In stationary flow, the applied k-ε-model in combination with a gradient-diffusion-model gives too small mixing rates as compared to LES and experiments. Furthermore, the LES computations of the T-junctions show, that Dean vortices occuring due to the curvature of the flow are broken up and dissipated only a few diameters downstream of the junction. The RANS computations do not predict this break-up, giving fundamentally different flow structures and mixing distributions. In pulsating flow, a resonance between the natural stabilities and the pulsation frequency is found by LES results, which could not be predicted by RANS.Computations of the flow in a Scania intake manifold with generic boundary con- ditions indicate, that inlet pulsations are important for the mixing process and that the smoothing effect of URANS is not adequate for accurate mixing computations. LES, on the other hand, is more promising, since it is able to capture the physics of pulsating flows much better. / QC 20111117

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