The diploma thesis deals with the issue of data transmission over power lines, focusing on simulation transmission functions. The theoretical part summarizes basic information on PLC technology and distribution networks, followed by analysis PLC simulator implemented in NS-third In the practical part of the thesis is described implementation of individual types of underground and overhead lines to the PLC simulator. Also been carried simulation scenarios for a simple topology and were designed own simulation scenarios for extended topology and simulations have been carried out various kinds of interference on communication.

Through the SARS-CoV-2 pandemic, it has become clear that the development of antivirals is essential for the health and wellbeing of the population. In this study, novel active site protease inhibitors against SARS-CoV-2 were tested for their inhibitory activity against the viral 3-Chymotrypsin like protease through the means of FRET based enzymatic assays. Additionally, Compound 104 targeting the NS2B-NS3 protease was tested against Zika virus through yield reduction assays as a means to assess whether these assays are suitable for the assessment of peptide hybrid compounds in Zika virus.Novel compounds against SARS-CoV-2 were screened and five of the selected six active compounds were found to inhibit the viral protease at a half-maximal inhibitory concentration (IC50) of below 0.075 µM.In Zika virus, the yield reduction assay was assessed and it was found that under the conditions tested, this assay is not suitable for the assessment of peptide hybrid compounds in Zika virus.The active novel compounds against SARS-CoV-2 should be taken for further assessment in cell based assays as the next step of development. Compound 104 should be assessed under different experimental conditions to identify whether different conditions can make this assay suitable for the intended use.

Hepatitis C viral infection is the major cause of acute hepatitis and chronic liver disease and remains the leading cause of liver transplants (NIH). An estimated 180 million people are infected globally (WHO). There is no vaccine available to prevent hepatitis C. The treatment with antiviral drugs is expensive, accompanied with various side effects and is limited only to those at risk of developing advanced liver disease. The treatment is also effective in only about 30% to 50% of treated patients and still a high percentage of patients are resistant to therapy. Therefore, there is an urgent need for the development of effective vaccine antigens and an efficacious HCV vaccine. The non-structural 3 protein of the hepatitis C virus is a multifunctional protein of the virus required for virus polyprotein processing and replication. Vaccine antigen production via chloroplast transformation system usually results in high expression levels and eliminates the possibility of contamination with vector sequences,human or animal pathogens. The HCV NS3 antigen was expressed in the chloroplast of Nicotiana tabacum var. Petit havana and LAMD-609. The 1.9kb NS3 gene was cloned into a chloroplast expression vector, pLD-Ct containing the 16S rRNA promoter, aadA gene coding for the spectinomycin selectable marker, psbA 5' untranslated region to enhance translation in the light and 3' untranslated region for transcript stability and trnI & trnA homologous flanking sequences for site specific integration into the chloroplast genome. Chloroplast integration of the NS3 gene was first confirmed by PCR. Southern blot analysis further confirmed site-specific gene integration and homoplasmy. The NS3 protein was detected in transgenic chloroplasts by immunoblot analysis. The NS3 protein was further quantified by ELISA. Maximum expression levels of NS3 up to 2% in the total soluble protein were observed even in old leaves, upon 3-day continuous illumination. These results demonstrate successful expression of the HCV non-structural 3 antigen in transgenic tobacco chloroplasts. Animal studies to test the immunogenecity of the chloroplast derived HCV NS3 will be performed using chloroplast derived NS3 antigen.

Mobil datakonsumtion har drastiskt ökat de senaste åren vilket belastar de existerande kommunikationsnätverken. I och med den ökade belastningen av existerande infrastrukturer krävs det nya kommunikationslösningar. Detta har i sin tur skapat ett behov för dataavlastning på fasta nätverk, exempelvis Wi-Fi-nätverk. I denna studie undersöker vi genom simuleringar hur vi kan underhålla ett storskaligt och dynamiskt Bluetooth meshnätverk i en miljö likt Stortorget under Malmöfestivalen. Vi implementerar en nätverkstopologi för Bluetooth, scatternettopologin, i nätverkssimulatorn NS-3 och utför simuleringar där vi provocerar förändringar i topologin. Resultaten av våra simuleringar visar på att nätverket lyckas återhämta sig vid förändring i topologin, att scatternettopologin minst klarar av 240 dynamiska mobila noder samt att max 3 noder påverkas vid förändringar i topologin för simuleringar av upp till 240 noder. / Mobile data consumption has drastically increased in the recent years which stress theexisting communication networks. As an effect of the increased load a demand for newcommunication solutions has arisen, creating a need for data offloading onto fixed networks such as Wi-Fi. In this thesis, we aim to study how to maintain and reconstruct a large and dynamic Bluetooth mesh network in an environment such as Stortorget during Malmöfestivalen. We implement a network topology specific for Bluetooth, the scatternet topology, in the network simulator NS-3 and run simulations in which we provoke changes in the network topology. The result of our simulations shows that the network is able to heal itself when the topology changes, that the scatternet topology can manage up to 240 dynamic mobile nodes and that at most 3 nodes are affected when the topology changes during simulations of up to 240 nodes.

Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal.

A hepatite viral causada pelo vírus da hepatite C (HCV) é um problema à saúde mundial e afeta cerca de 170 milhões de pessoas. O caso crônico da doença resulta em cirrose hepática e a maioria dos pacientes tratados não desenvolve uma resposta imune satisfatória. A proteína não estrutural 3 (NS3) pode estimular uma resposta celular que auxilia a resposta nos infectados. Nosso trabalho desenvolveu duas pseudopartículas virais que carregam um material genético para a protease da NS3 do HCV. Um dos sistemas, a HCVpp é constituída por proteínas do vírus da leucemia murina e outras do HCV. E o outro sistema, a partícula viral é baseada no Semliki Forest Virus (SFV). As células HEK293T e BHK-21 foram transfectadas para a formação das pseudopartículas HCVpp-NS3p1a e SFV-NS3p1a, respectivamente. Essas partículas foram quantificadas pela presença do material genético da NS3 por qRT-PCR, atingindo uma produção aproximada de 4x105 partículas HCVpp-NS3p1a/mL e 2,5x107 partículas SFV-NS3p1a/mL. Essas partículas foram utilizadas para infecção de células HuH-7.0 e BHK-21. / Viral hepatitis caused by the hepatitis C virus (HCV) is a global health problem, affecting about 170 million people. The chronic case of the disease results in liver cirrhosis and most patients do not develop a satisfactory immune response. The nonstructural protein 3 (NS3) can stimulate a cellular response that helps answer the infected. Our work has developed two viral pseudoparticles who carry a genetic material for the HCV NS3 protease. One of the systems is constituted by the HCVpp proteins of murine leukemia virus and other HCV. The other system, the viral particle is based on the Semliki Forest Virus (SFV). The HEK293T and BHK-21 cells were transfected for forming the pseudoparticles HCVpp-NS3p1a and SFV-NS3p1a, respectively. These particles were quantified by the presence of genetic material of NS3 by qRT-PCR, reaching a production of about 4x105 HCVpp-NS3p1a particles/mL and 2,5 x107 SFV-NS3p1a particles /mL. These particles were used for infection of Huh-7.0 cells and BHK-21.

Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal

A hepatite viral causada pelo vírus da hepatite C (HCV) é um problema à saúde mundial e afeta cerca de 170 milhões de pessoas. O caso crônico da doença resulta em cirrose hepática e a maioria dos pacientes tratados não desenvolve uma resposta imune satisfatória. A proteína não estrutural 3 (NS3) pode estimular uma resposta celular que auxilia a resposta nos infectados. Nosso trabalho desenvolveu duas pseudopartículas virais que carregam um material genético para a protease da NS3 do HCV. Um dos sistemas, a HCVpp é constituída por proteínas do vírus da leucemia murina e outras do HCV. E o outro sistema, a partícula viral é baseada no Semliki Forest Virus (SFV). As células HEK293T e BHK-21 foram transfectadas para a formação das pseudopartículas HCVpp-NS3p1a e SFV-NS3p1a, respectivamente. Essas partículas foram quantificadas pela presença do material genético da NS3 por qRT-PCR, atingindo uma produção aproximada de 4x105 partículas HCVpp-NS3p1a/mL e 2,5x107 partículas SFV-NS3p1a/mL. Essas partículas foram utilizadas para infecção de células HuH-7.0 e BHK-21. / Viral hepatitis caused by the hepatitis C virus (HCV) is a global health problem, affecting about 170 million people. The chronic case of the disease results in liver cirrhosis and most patients do not develop a satisfactory immune response. The nonstructural protein 3 (NS3) can stimulate a cellular response that helps answer the infected. Our work has developed two viral pseudoparticles who carry a genetic material for the HCV NS3 protease. One of the systems is constituted by the HCVpp proteins of murine leukemia virus and other HCV. The other system, the viral particle is based on the Semliki Forest Virus (SFV). The HEK293T and BHK-21 cells were transfected for forming the pseudoparticles HCVpp-NS3p1a and SFV-NS3p1a, respectively. These particles were quantified by the presence of genetic material of NS3 by qRT-PCR, reaching a production of about 4x105 HCVpp-NS3p1a particles/mL and 2,5 x107 SFV-NS3p1a particles /mL. These particles were used for infection of Huh-7.0 cells and BHK-21.

<p>This thesis describes the design and synthesis of compounds that are</p><p>intended to inhibit serine and aspartic proteases. The first part of the text deals with preparation of inhibitors of the hepatitis C virus (HCV) NS3 serine protease. Hepatitis C is predominantly a chronic disease that afflicts about 170 million people worldwide. The NS3 protease, encoded by HCV, is essential for replication of the virus and has become one of the main targets when developing drugs to fight HCV. The inhibitors discussed here constitute surrogates for the widely used <em>N</em>-acyl-hydroxyproline isostere designated 4-hydroxy-cyclopentene. The stereochemistry of the 4-hydroxy-cyclopentene scaffold was determined by nuclear overhauser effect spectroscopy (NOESY) and the regiochemistry by heteronuclear multiple bond correlation (HMBC). The scaffold was decorated with different substituents to obtain both linear and macrocyclic HCV NS3 protease inhibitors that display low nanomolar activity. The second part of the thesis describes the design and synthesis of potential aspartic protease inhibitors. The hydroxyethylene motif was used as a noncleavable transition state isostere. The synthetic route yielded a pivotal intermediate with excellent stereochemical control, which was corroborated by NOESY experiments. This intermediate can be diversified with different substituents to furnish novel aspartic protease inhibitors.</p> / Report code: LIU-TEK-LIC-2006:45

Structure-based drug design and combinatorial chemistry play important roles in the search for new drugs, and both these elements of medicinal chemistry were included in the present studies. This thesis outlines the synthesis of protease inhibitors against thrombin and the HCV NS3 protease, as well as the synthesis of a combinatorial library using solid phase chemistry.In the current work potent thrombin inhibitors were generated based on the D-Phe-Pro-Arg motif incorporating cyclopentene and cyclohexene scaffolds that were synthesized by ring-closing metathesis chemistry. A structure-activity relationship study was carried out using the crystallographic results for one of the inhibitors co-crystallized with thrombin. HCV NS3 protease inhibitors comprising the proline bioisostere 4-hydroxy-cyclopent-2-ene-1,2-dicarbboxylic acid were synthesized displaying low nanomolar activity. The stereochemistry and regiochemistry of the scaffolds were determined by NOESY and HMBC spectra, respectively. The final diastereomeric target compounds were isolated and annotated by applying TOCSY and ROESY NMR experiments. Furthermore, a 4-phenyl-2-carboxypiperazine targeted combinatorial chemistry library was synthesized to be used early in the lead discovery phase. This was done using a scaffold that was synthesized by palladiumcatalyzed aromatic amination chemistry and subsequently derivatized with eight electrophiles and ten nucleophiles.