Yes / Background: The HOX genes are a family of transcription factors that help to determine cell and tissue identity during early development, and which are also over-expressed in a number of malignancies where they have been shown to promote cell proliferation and survival. The purpose of this study was to evaluate the expression of HOX genes in prostate cancer and to establish whether prostate cancer cells are sensitive to killing by HXR9, an inhibitor of HOX function. Methods: HOX function was inhibited using the HXR9 peptide. HOX gene expression was assessed by RNA extraction from cells or tissues followed by quantitative PCR, and siRNA was used to block the expression of the HOX target gene, cFos. In vivo modelling involved a mouse flank tumour induced by inoculation with LNCaP cells. Results: In this study we show that the expression of HOX genes in prostate tumours is greatly increased with respect to normal prostate tissue. Targeting the interaction between HOX proteins and their PBX cofactor induces apoptosis in the prostate cancer derived cell lines PC3, DU145 and LNCaP, through a mechanism that involves a rapid increase in the expression of cFos, an oncogenic transcription factor. Furthermore, disrupting HOX/PBX binding using the HXR9 antagonist blocks the growth of LNCaP tumours in a xenograft model over an extended period. Conclusion: Many HOX genes are highly over-expressed in prostate cancer, and prostate cancer cells are sensitive to killing by HXR9 both in vitro and in vivo. The HOX genes are therefore a potential therapeutic target in prostate cancer. / The authors gratefully acknowledge the support of the Prostate Project charity (UK).

The zebrafish visual system relies on positional information in the retina and optic tectum, so that the spatial fidelity of light signals that enter the eye are preserved for visual processing. This positional information is essential for ordered topographic mapping of retinal ganglion cell axons. Spatial information in the retina and tectum relies on discrete signaling pathways that regulate polarized expression of axon guidance molecules in distinct domains in both the retina and tectum, thereby ensuring that accurate topographic maps are created. In this thesis, I have investigated the function of two families of transcription factors, Pbx and Meis, as well as a growth factor of the Bmp family, Gdf6a, in specifying positional identity in the zebrafish visual system. I demonstrate that two partially redundant pbx genes, pbx2 and pbx4, along with members of the meis family, are required for patterning of the dorsal retina and tectum in zebrafish. Embryos lacking these critical transcription factors exhibit retinal ganglion cell axon outgrowth errors, which are likely the result of tectal mis-patterning. Bone morphogenetic protein (Bmp) growth factors regulate dorsal retinal identity in vertebrate models, but the developmental timing of this signaling remains unclear. In this thesis, I investigate the functions of two zebrafish Bmps, Gdf6a and Bmp4, during initiation of dorsal retinal identity. Knockdown of zebrafish Gdf6a blocks initiation of dorsal marker expression, while knockdown of Bmp4 produces no discernable retinal phenotype. These data, combined with analyses of embryos ectopically expressing Bmps, demonstrate that Gdf6a is necessary and sufficient for initiation of dorsal retinal identity, and loss of such identity leads to errors in retinal ganglion cell topographic mapping. Finally, I demonstrate that gdf6a is required for numerous embryonic processes in addition to dorsal retina specification. Gdf6a in required for eye growth, as loss of Gdf6a function leads to microphthalmia. I have obtained preliminary evidence that this growth factor is also required for development of the lens and axial skeleton. Furthermore, many of these phenotypes are similar to those seen in human patients with mutations in GDF6, highlighting the importance of understanding the function of this growth factor in model organisms. / Molecular Biology and Genetics

Erprobung der Open-Source VoIP-Lösung Asterisk - dabei wurde das IAX Protokoll und der Stand der SIP/H.323 Integration bewertet. Eine Übersicht der nutzbaren Clienten runten diese Studienarbeit ab.

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Approved for public release, distribution is unlimited / The purpose of this thesis is to perform a cost-effectiveness analysis on proposals, submitted by vendors, for a telecommunication system. This thesis will be used as a guide in the decision-making process of choosing the most cost-effective system for the Bachelor Officers Quarters of the Naval Postgraduate School. In addition to cost-effectivness, this study includes a discussion of the analysis criteria, a review of the Statement of Work and an evaluation of the lease/purchase decision.

This diploma dissertation is dealing with the VoIP software exchange Asterisk. In the dissertation there are described its abilities and possible ways of its configuration. Special attention is given to the signalling protocol SIP, which is described in one of the chapters. Within this dissertation a dial plan, which demonstrates the technique of dial plan creating, was created. Within the boundaries of the dialplan following services could be found: a voicemail, conference, Interactive Voice Response and call queues. Configuration files, with the help of which the exchange is configurated, are described in my dissertation as well. Finally, three laboratory assignments for purposes of the subject Multimedia Services are mentioned. Their main aim is to familiarise students with the creation of SIP accounts in the exchange, their mutual connections, defining the Interactive Voice Response and forming a new call centre.

Short Message Service (shortly SMS) is the most widely used type of communication systems. The main advantages are that allow a fast exchange of messages between devices, a very good availability through GSM and a reasonable price. Nowadays the SMS service support has expanded to include other technologies such as a service of the information navigation and the remote connection. The master‘s thesis concentrates on the Short Message Service, deals with basic principles and statements using by this service. The topic of the thesis is software PBX Asterisk and its possibility of SMS implementation, especially verification of SMS processing goes through the PSTN. After the basic introduction the master‘s work deals with the installation and configuration of the server. The main focus is on an installation of the operating system with an additional pack including necessary libraries and modules for a correct working of the server. The following section is paying attention to the Asterisk server configuration, especially a hardware card installation which is necessary for a connection with analog telephones, done by Bluetooth connections, set up user’s profiles of the SIP protocol and create a dial plan. This is followed by a verification of SMS option of the implementation and communication with GSM modem which is used as a gate for an exchange SMS between PSTN and GSM network. The last chapter of this master‘s thesis comes with the aimed results.

Yes / The HOX and PBX gene families encode transcription factors that have key roles in establishing the identity of cells and tissues in early development. Over the last 20 years it has become apparent that they are also dysregulated in a wide range of solid and haematological malignancies and have a predominantly pro-oncogenic function. A key mode of transcriptional regulation by HOX and PBX proteins is through their interaction as a heterodimer or larger complex that enhances their binding affinity and specificity for DNA, and there is growing evidence that this interaction is a potential therapeutic target in malignancies that include prostate, breast, renal, ovarian and lung cancer, melanoma, myeloma, and acute myeloid leukaemia. This review summarizes the roles of HOX and PBX genes in cancer and assesses the therapeutic potential of HOX/PBX dimer inhibition, including the availability of biomarkers for its application in precision medicine.

Retinoic acid (RA) is critical for embryonic development and cell differentiation. Previous work in our laboratory has shown that blocking the RA-dependent increase in Pre-â cell leukemia transcription factors (PBX) mRNA and protein levels in P19 cells prevents them from differentiating to either endodermal or neuronal cells. This suggests that PBX is an important regulator of RA-induced differentiation of P19 cells. A microarray analysis was performed to identify PBX regulated genes, utilizing the empty vector P19 (TO3) and antisense to PBX (AS2) cell lines, during RA-induced differentiation of P19 cells into endodermal or neuronal cells. Among the genes identified by the microarray, Dosage-sensitive sex reversal, adrenal hypoplasia critical region, on chromosome X, gene 1 (DAX-1) and steroidogenic factor 1 (SF-1) were identified to be directly or indirectly regulated by PBX. Both DAX-1 and SF-1 proteins have only recently been reported to be present in preimplantation mouse embryos prior to the expression of steroidogenic enzymes, suggesting they may play a role in early mouse embryogenesis. To determine the roles of DAX-1 and SF-1 during RA-dependent differentiation, P19 cells that inducibly express either FLAG-DAX-1 or FLAG-SF-1 upon removal of doxicyclin were prepared. We found that overexpression of FLAG-DAX-1 had no effect on the RA-induced differentiation of P19 cells. However, FLAG-SF-1 overexpression prevented the RA-dependent loss of Oct-4, DAX-1 and the increase in COUP-TFI, COUP-TFII, and Ets-1 mRNA levels during the commitment stages of both endodermal and neuronal differentiation. Surprisingly, continued expression of SF-1 for seven days caused a RA-independent loss of Oct-4 protein. However, cells which continued to express SF-1 for seven days did not terminally differentiate into endodermal or neuronal cells in response to RA treatment. In addition, we found evidence for a feedback loop, where PBX reduces SF-1 mRNA expression and continued SF-1 expression blocks the RA-dependent increase in PBX protein levels. Our findings suggest that SF-1 plays a novel role in P19 cells where its level of expression is critical for the differentiation state of the cells. At basal levels SF-1 maintains the pluripotent state of the cells, while SF-1 levels must be dramatically reduced for cells to differentiate into both endodermal and neuronal cells upon RA treatment. However, at elevated levels above basal, SF-1 inhibits Oct-4 expression and leads to the induction of the expression of steroidogenic enzymes with a pattern consistent with adrenal cells in a RA-independent fashion. Taken together these data suggest that SF-1 plays a much more dynamic role in P19 cells than previously reported. / Biochemistry

Šiame dokumente nagrinėjama tyrimo sritis susijusi su mobiliojo ryšio operatoriams skirtomis virtualių telefoninių stotelių sistemomis. Analitinėje darbo dalyje atsakomi pagrindiniai šio projekto klausimai, pristatomos bendros idėjos ir vėliau apžvelgiama panašių sistemų specifika. Projektinėje dalyje į sistemą pažvelgiama iš architektūros pusės. Sukonkretinami priimti sprendimai ir pateikiamas jų realizacijos aprašymas. Tiriamoje ir eksperimentinėje darbo dalyje atliekamas dviejų telekomunikacijoms skirtų platformų tyrimas – jNetX OCFS ir Mobicents JAIN SLEE. Įvertinama sistemų kokybė ir pateikiamas apibendrintas platformų vaizdas kartu su išvadomis ar vertą esamą sistemą migruoti į naują platformą ir kokios kliūtys gali kilti tai atliekant. / The objective of this project was to develop software for mobile network operators, which provides virtual private branch exchange functionality and has operator console for its control. During its execution, the analysis of design and technology solutions was performed. The architecture of the developed software is based mainly on the principle of client server design and JAIN SLEE specification. Quality and feature anlysis of two competing plaforms was performed – jNetX OCFS and Mobicents JAIN SLEE. Main objective of analysis was to find out if Mobicents JAIN SLEE is feasible replacement for jNetX OCFS, analysis showed that it is.