Chemokines are chemotactic cytokines, which mediate cell trafficking and play a key role in mobilisation of leukocytes. More recently, chemokines and their cognate receptors have been described as key players in different aspects of cancer biology contributing to proliferation, angiogenesis and metastasis. In particular, chemokines CCL19 and CCL21 acting on their associated receptor CCR7 are postulated to be key drivers of lymph node metastasis in a number of malignancies including breast, colon, gastric, & thyroid cancers. It has been reported that the cleavage of the pre-cysteine bridge N-terminal residues of CCL21 (SDGGAQD) and of CCL19 (GTNDAED) renders both peptides incapable of fully activating CCR7. However, little is known about the nature of the interactions that occur between the N-terminal residues of CCL19 or CCL21 and the CCR7 receptor, or the role they have in activation of CCR7. The aim of this study is to investigate the role of the residues in the N-terminus of CCL19 and in particular CCL21 in the context of CCR7 activation and to use this information in the discovery of novel CCR7 antagonists or agonists. To achieve this, we synthesised a number of short (three to seven amino acids) peptides and peptidomimetics inspired by the seven N-terminal amino acid residues of CCL19 and CCL21 and pharmacologically characterised their ability to activate CCR7 or block the activation of CCR7 using a number of in vitro assays such as calcium flux, trans-well (Boyden chamber), and Western blotting. We also carried out computational studies to better understand and predict the activity of these peptides. Our results demonstrate that some of these peptides are indeed capable of acting as agonists or antagonists of CCR7. / Kuwait Health Ministry and Kuwait Civil Services Commission

Industrial innovation is mostly driven by miniaturization. As a result of remarkable technological advancements in the fields of equipment, materials and production processes, transistor, the fundamental active component in conventional electronics, has shrunk in size. Semiconductor technology is unique in that all performance metrics are enhanced, while at the same time unit prices are reduced. Moore’s Law, which predicts that the number of components per chip will double every two years, was established in 1965, and the industry has been able to keep up with this prophetic prognosis since. Thermal management, on the other hand, has become a key limiting factor for current electronic circuits and is set to put a stop to Moore’s Law. Given the fact that complementary metal oxide semiconductor (CMOS) scaling is reaching fundamental limits, there are several new alternative processing devices and architectures that have been investigated for both traditional integrated circuit (IC) technologies and novel technologies, including new technologies aimed at contributing to advances in scaling progress and cost reductions in manufacturing operations in the coming decades. These factors will encourage the development of new information processing and memory systems, new technologies for integrating numerous features heterogeneously and new system architectural design layouts, among other things. Energy efficiency is advantageous from a sustainability perspective and for consumer electronics, for which fewer power-hungry components mean longer times between charges and smaller batteries. The creation of novel chip-scale tools that can aid in the transfer of information across optical frequencies and microscale photonics between nanoscale electronic devices is now a possibility. Bridging this technological gap may be achieved by plasmonics. The incorporation of plasmonic, photonic and electrical components on a single chip may lead to a number of innovative breakthroughs. Photonic integrated circuits (PICs) enable the realization of ultra-small, high-efficiency, ultra-responsive and CMOS-compatible devices that can be used in applications ranging from optical wireless communication systems (6G and beyond) and supercomputers to health and energy.   This thesis provides a platform from which to design nanoplasmonic devices while facilitating high-transmission and/or absorption efficiency, miniaturized size and the use of near-infrared (NIR) wavelengths for telecom applications. With a significant amount of Internet traffic transmitted optically, communication systems are further tightening the requirements for the development of new optical devices. Several new device structures based on the metal-insulator-metal (MIM) plasmonic waveguide are proposed and investigated using performance metrics. The transmission line theory (TLM) from microwave circuit theory and coupled mode theory (CMT) is studied and employed in the design process of the nanostructures, in particular to address the losses in plasmonic-based devices, which has been the major factor hampering their widespread usage in communication systems. By taking advantage of well-established microwave circuit theory (through new design that paves the way for mitigating these losses and enabling efficient transmission of power flow in the optical devices), we have suggested a number of high-transmission efficiency nanodevices that offer highly competitive performance compared with other platforms. As a result, a promising future for plasmonic technology, which would enable design and fabrication of multipurpose and multifunctional optical devices that are efficient in terms of losses, footprint and capability of integrating active devices, is anticipated. / Branschinnovation drivs främst av miniatyrisering. Som ett resultat av anmärkningsvärda tekniska framsteg inom områdena utrustning, material och produktionsprocesser kunde transistoren, den grundläggande aktiva komponenten i samtida elektronik, krympa i storlek. Halvledarteknik är unik genom att alla prestandamått förbättras, samtidigt som enhetspriserna sänks. Moores Lag, som förutspår att antalet komponenter per chip skulle fördubblas vartannat år, inrättades 1965, och branschen har kunnat hålla jämna steg med den profetiska prognosen sedan dess. Termisk hantering, å andra sidan, har blivit en viktig begränsande faktor för nuvarande elektroniska kretsar, och är inställd på att sätta stopp för Moores Lag. Med tanke på att CMOS-skalningen (Complementary Metal Oxide Semiconductor) når grundläggande gränser finns det flera nya alternativa bearbetningsanordningar och arkitekturer som har undersökts för både traditionell integrerad kretsteknik och ny teknik. Ny teknik som syftar till att bidra till framsteg i skalningen av framsteg och kostnadsminskningar i tillverkningsverksamheten under de kommande årtiondena. Dessa faktorer uppmuntrar utvecklingen av nya informationsbehandlings- och minnessystem, ny teknik för att integrera många funktioner heterogent och nya systemarkitekturdesignlayouter, bland annat. Energieffektivitet är fördelaktigt ur ett hållbarhetsperspektiv och för hemelektronik, där färre krafthungriga elektroniker innebär längre tid mellan laddningar och stimulerar för ett mindre energilagringssystem ombord. Skapandet av nya chip-scale verktyg som kan bidra till överföring av information över optiska frekvenser och mikroskala fotonik mellan elektroniska enheter i nanoskala är nu en möjlighet. Överbrygga denna tekniska klyfta kan uppnås av plasmonics. Införlivandet av plasmoniska, fotoniska och elektriska komponenter på ett enda chip kan leda till ett antal innovativa genombrott. Fotoniska integrerade kretsar (PIC-enheter) möjliggör förverkligande av ultrasmå, högeffektiva, ultraresponsiva och CMOS-kompatibla enheter som kan användas i applikationer som sträcker sig från optiska trådlösa kommunikationssystem (6G och därefter), superdatorer till hälso- och energiändamål. Denna avhandling ger en plattform för att designa nanoplasmoniska enheter samtidigt som den innehåller hög överförings- och eller absorptionseffektivitet, miniatyriserad storlek och vid önskade våglängder av nära infraröd (NIR) för telekomapplikationer. Med den betydande mängden Internettrafik som överförs optiskt skärper kommunikationssystemen ytterligare kraven för utveckling av nya optiska enheter. Flera nya enhetsstrukturer baserade på metall-isolator-metall (MIM) plasmonisk vågledare föreslås och numeriskt undersöks. Överföringslinjeteorin (TLM) från mikrovågskretsteori och kombinationslägesteori (CMT) studeras och används i nanostrukturerna. För att ta itu med de förluster i plasmonbaserade enheter som har varit den viktigaste parametern som hindrade deras utbredda användning i kommunikationssystem, genom att dra nytta av den väletablerade mikrovågskretsteorin (genom ny design som banar väg för att mildra förlusterna och möjliggöra effektiv överföring av kraftflödet i den optiska enheten).  Vi har framgångsrikt föreslagit ett antal nanodevices med hög överföringseffektivitet som erbjuder en mycket konkurrenskraftig prestanda jämfört med andra plattformar. Som ett resultat förväntar vi oss en lovande framtid för plasmonisk teknik som skulle möjliggöra design och tillverkning av mångsidiga och multifunktionella optiska enheter som är effektiva när det gäller förluster, fotavtryck och förmåga att integrera aktiva enheter. / <p>Vid tidpunkten för framläggandet av avhandlingen var följande delarbeten opublicerade: delarbete II inskickat, III, IV, V manuskript.</p><p>At the time of the licentiate defence the following papers were unpublished: paper II submitted, III, IV, V manuscript.</p>

O presente trabalho apresenta metodologias utilizando a p-benzoquinona (PBQ) para a determinação de proteínas totais em diversas matrizes. As metodologias propostas foram comparadas com os métodos recomendados ou os mais utilizados, conforme o caso. O método aqui proposto, para determinação de proteínas totais em plasma sangüíneo, foi comparado com o método de biureto, mostrando-se adequado e com sensibilidade dez vezes maior que a do biureto. Para a determinação de proteínas totais em diversos tecidos de rato, o método proposto foi comparado com os métodos de Hartree e FFDW, e apresentou resultados mais próximos do FFDW do que o método de Hartree e, também, mostrou ser mais rápido, barato e de fácil realização. O método desenvolvido para determinação de proteínas totais em leite em pó desnatado foi comparado com os métodos de Kjeldahl e Lowry e cols., sendo mais simples e rápido que as metodologias de Lowry e Kjeldahl. Para determinação de amino grupos livres em síntese de peptídeos em fase sólida, a metodologia proposta foi comparada com o método de Kaiser e cols. O método proposto apresentou diversas vantagens sobre o método de Kaiser, sendo estas: o método é sensível a prolina, não precisa preparar nenhuma solução, não apresenta falso positivo para histidina e é rápido. / The present thesis describes the utilization of p-benzoquinone (PBQ) for assay of total protein in several samples. The methods presented here were compared with those mostly used or recommended depending on the case. For determination of total proteins in the blood plasma, the proposed method was compared with biuret method, and it was 10 times more sensitive than biuret method and convenient method for determination of total proteins in plasma. The assay of total proteins in several rat tissues with the proposed method, was compared with Hartree and FFDW methods, and it shows closer proteins content to FFDW method than Hartree method, besides it was faster, less expensive and easier to be used than Hartree method. The method developed for determination of total proteins in skin milk powder, was compared with Kjeldahl and Lowry methods and showed to be more simple and faster than these methods. For determination of free amino groups in solid phase peptide synthesis, the proposed method was compared with Kaiser method. The proposed method showed several advantages than Kaiser method, such as: it is sensitive for proline, it is not necessary to prepare any solution and it does not show a false positive test for histidine.

Despite the Swedish Prison and Probation Service (SPPS) are a pioneer on the global arena regarding the area of corrections, generally little is known of what they do in Sweden as well as internationally. This study will explore the SPPS implementation of prison development in Somalia, which will be done through interviews with seconded personnel and others within the Swedish government that have connections to the prison development in Somalia. The findings were able to answer the research questions for this thesis, namely what the SPPS are doing internationally, what they are doing in Somalia and lastly if they have seen any results in Somalia. In the analysis, the middle power theory was used through an abductive approach to see if the SPPS fulfilled the criterions for the theory namely moral power, multilateralism and conflict management. It is concluded that the SPPS work in Somalia have been effective. They have contributed considerably to the local development and the seconded personnel has also learnt lessons for life which they can use also in their further carriers. Through their contacts, which they have established, they might also contribute further bilaterally even in the event of a withdrawal from the United Nations.

No description available.

O presente trabalho apresenta metodologias utilizando a p-benzoquinona (PBQ) para a determinação de proteínas totais em diversas matrizes. As metodologias propostas foram comparadas com os métodos recomendados ou os mais utilizados, conforme o caso. O método aqui proposto, para determinação de proteínas totais em plasma sangüíneo, foi comparado com o método de biureto, mostrando-se adequado e com sensibilidade dez vezes maior que a do biureto. Para a determinação de proteínas totais em diversos tecidos de rato, o método proposto foi comparado com os métodos de Hartree e FFDW, e apresentou resultados mais próximos do FFDW do que o método de Hartree e, também, mostrou ser mais rápido, barato e de fácil realização. O método desenvolvido para determinação de proteínas totais em leite em pó desnatado foi comparado com os métodos de Kjeldahl e Lowry e cols., sendo mais simples e rápido que as metodologias de Lowry e Kjeldahl. Para determinação de amino grupos livres em síntese de peptídeos em fase sólida, a metodologia proposta foi comparada com o método de Kaiser e cols. O método proposto apresentou diversas vantagens sobre o método de Kaiser, sendo estas: o método é sensível a prolina, não precisa preparar nenhuma solução, não apresenta falso positivo para histidina e é rápido. / The present thesis describes the utilization of p-benzoquinone (PBQ) for assay of total protein in several samples. The methods presented here were compared with those mostly used or recommended depending on the case. For determination of total proteins in the blood plasma, the proposed method was compared with biuret method, and it was 10 times more sensitive than biuret method and convenient method for determination of total proteins in plasma. The assay of total proteins in several rat tissues with the proposed method, was compared with Hartree and FFDW methods, and it shows closer proteins content to FFDW method than Hartree method, besides it was faster, less expensive and easier to be used than Hartree method. The method developed for determination of total proteins in skin milk powder, was compared with Kjeldahl and Lowry methods and showed to be more simple and faster than these methods. For determination of free amino groups in solid phase peptide synthesis, the proposed method was compared with Kaiser method. The proposed method showed several advantages than Kaiser method, such as: it is sensitive for proline, it is not necessary to prepare any solution and it does not show a false positive test for histidine.

The diploma thesis deals with the development of a new method of synthetic peptide separation using electrostatic binding. It deals with the development of a multi-charged anchored linker attachable to a synthetic peptide after its synthesis on solid phase. Subsequently, it investigates the separation using electrostatic binding; however, after peptide cleavage from the anchored linker and Boc deprotection with TFA, the peptide formed so strong electrostatic interactions with the cation exchanger that we were unable to recover it. The thesis is finished with discussion and method improvement proposal. Key words: peptide separation, solid-phase peptide synthesis, SPPS, electrostatic binding

Targeted radionuclide therapy is becoming a widely used cancer treatment strategy. By radiolabeling receptor-specific peptides, cancer cells overexpressing the receptor can be selectively targeted, and the cytotoxic radionuclide can be delivered to the target cell or tissue for therapeutic or diagnostic purposes. Bombesin analogues have been previously developed and utilized to target the gastrin-releasing peptide receptor (GRPR), a receptor commonly overexpressed in prostate cancer cells. The RM26 analogue derived from the native bombesin is an antagonistic ligand of GRPR and a possible candidate for targeted radiotherapy. Prolonging the half-life of the molecule is an important aspect of developing a new protein therapeutic. Using albumin binding domain (ABD) for this purpose is an emerging strategy in recent years. ABD is able to bind to serum albumin and thus remains in the blood circulation for a long period of time. It is also a scaffold for protein engineering efforts and by coupling receptor-specific ligands to ABD, the target-specific binding along with extended in vivo halflife can be achieved. In this project, an RM26 analogue with a PEG linker and ABD with a DOTA chelator for future radiolabeling were synthesized with solid phase peptide synthesis (SPPS), conjugated, purified by RP-HPLC and analyzed by mass spectrometry. The binding properties of the conjugate were evaluated by SPR-based biosensory studies, and further experiments are planned for the testing the product and its potential application in radionuclide therapy. / Riktad radioterapi är en allt vanligare metod för behandling av cancer. Genom att radioinmärka receptor-specifika peptider kan dessa selektivt levereras till tumörceller som uttrycker receptorn. Radioterapi kan användas för diagnostik eller terapi, beroende på kopplad radionuklid. Bombesinanaloger har utvecklats och använts för att selektivt binda gastrinfrisättande peptidreceptor (gastrin-releasing peptide receptor, GRPR), en receptor som ofta är överuttryckt i prostatacancer. Bombesinanalogen RM26, som har sitt ursprung från nativt bombesin, är en antagonist till GRPR och kan möjligen användas för riktad radioterapi av prostatacancer. Vid utvecklingen av nya proteinläkemedel är halveringstiden i serum en viktig aspekt. En nyligen utvecklad strategi för att förlänga halveringstiden i serum är fusion av det  tumörspecifika proteinet till en albumin-bindande domän (ABD). ABD binder till albumin, ochsåledes kan fusionsproteinet bevaras i blodcirkulationen under en längre tid. I detta projekt, har både RM26 med en PEG-linker, och ABD med en DOTA kelator syntetiserats med fastfaspeptidsyntes (solid phase peptide synthesis, SPPS). RM26-PEG och DOTA-ABD har därefter konjugerats, renats med RP-HPLC och analyserats med massspektrometri. Bindning till albumin har utvärderats med ytplasmonresonans (surface plasmon resonance, SPR). Vidare studier planeras för att utvärdera peptid-proteinkonjugatet och dess potential för riktad radioterapi.

Yaku'amide A shows a unique inhibitory profile against a series of 39 human cancer cell lines (JFCR39). In our efforts to synthesize yaku'amide A, we have optimized our regioselective base-free aminohydroxylation method with a series of nitrogen sources, developed a chiral reagent-mediated aminohydroxylation strategy and chemoselective deprotections of the resulting aminohydroxylation product, and explored a stereospecific E2 dehydration and O-N acyl transfer sequence. In addition, we have prepared the right-hand tetrapeptide and the NTA subunit. For our bulky α,β-dehydroamino acids project, we have developed strategies to incorporate α,β-dehydroamino acids such as ΔVal and ΔEnv into small synthetic peptides via Solid Phase Peptide Synthesis (SPPS). We have also prepared two analogues of a monomeric helical peptide with 13 residues.

The nature of surface-enhanced Raman scattering (SERS) on nanostructured surfaces is explored using both inorganic and organic-based systems and a variety of environmental perturbation mechanisms. Experimental optical characterisation systems are developed and existing systems extended to facilitate this exploration. SERS of inorganic semiconducting quantum dots (QDs) is observed for the first time, paving the way for their use as spatially well-defined SERS markers. Tuning of the Raman excitation wavelength allows comparison between resonance and nonresonance QD SERS and identifies enhancement due to the plasmonic nanostructure. A gentle mechano-chemical process (carbon dioxide snow jet) is used to rearrange adsorbed organic thiol monolayers on a gold plasmonic nanostructure. The necessity of nanoscale roughness to the large SERS enhancement on pit-like plasmonic nanostructures is shown and demonstrates a new method to boost SERS signals (> 500 %) on plasmonic nanostructures. A multiplexed time-varied exposure technique is developed to track this molecular movement over time and highlights the different origins of the SERS peak and its accompanying background continuum. Using low-temperature cryogenics (down to 10 K) the SERS peak and background continuum intensity are shown to increase as the plasmonic metal damping reduces with temperature. Temperature dependent measurements of QD (resonance) SERS are shown to have strong wavelength dependence due to the excitonic transitions in QDs. Changes to the QD fluorescence at low temperature allows striking comparison between the Raman and fluorescence processes. The role of charge transfer and electromagnetic enhancement in the SERS intensity of p-aminothiophenol (pATP) is investigated on nanostructured plasmonic surfaces coupled to metallic nanoparticles. The results support the importance of charge transfer effects to the SERS of pATP, and highlight the difference between those of electromagnetic origin. Addition of nanoparticles to the nanostructured surface was seen to enhance SERS signals by up to 100×.