1,271 research outputs found
Letter from Frederic L. Kirgis, U.S. National Park Service
No full textLetter from solicitor Frederic L. Kirgis on behalf of his clients filing claims in regards to the fire started on government-owned apartments in the Grand Canyon
A Spin Wave Based Approximate 4:2 Compressor Seeking the most energy-efficient digital computing paradigm
No full textsponsorship: This work received funding from the European Union's Horizon 2020 research and innovation program within the Future and Emerging Technologies Open project Spin Wave Computing for Ultimately-Scaled Hybrid Low-Power Electronics, under grant 801055. It has also been partially supported by IMEC's industrial affiliate program on beyond-CMOS logic. Frederic Vanderveken acknowledges financial support from Flanders Research Foundation through grant 1S05719N. (European Union's Horizon 2020 research and innovation program within the Future and Emerging Technologies Open project Spin Wave Computing for Ultimately-Scaled Hybrid Low-Power Electronics|801055, IMEC's industrial affiliate program on beyond-CMOS logic, Flanders Research Foundation|1S05719N)status: Publishe
The Early History of the Fraser River Mines
No full textby Frederic W. Howay.Memoirs (Provincial Archives of British Columbia) ; 6
The Novels of Harold Frederic
No full textI do not intend to defend the obviously untenable thesis that Frederic was a great writer and is not appreciated because of the nature of his subject matter. The author of The Damnation of Theron Ware seldom shows any sign of genius. What Frederic does, and often in a rather workmanlike manner, is tell a story of small-town and country people in upper New York state. In his early works, Seth\u27s Brother\u27s Wife and The Lawton Girl, the author writes about things he knows and has done. The works written about the same time as the two mentioned have a delightful simplicity and naïveté, and incidentally come very close to the realistic tradition in the novel. The majority of Frederic\u27s later works are tinged with a pseudo-sophistication, an artiness which just does not belong, and these elements detract from such an otherwise good thing as The Damnation of Theron Ware
Danube River Development Strategy: Interim Report
No full textThe Danube is an essential Inland Water Transport (IWT) corridor, particularly for the hinterland connection for the Port of Constantza. This port became one of the largest and busiest ports on the Black Sea, due to its strategic location at the cross roads of Europe and Asia and due to its capacity to handle large volumes of different types of cargoes. With the ongoing economic reforms in Romania it is expected that the Port of Constantza will develop into a gateway for Eastern and Central Europe and efficient IWT hinterland connections are therefore required. The project "Danube River Development Strategy" aims to formulate a strategy and to define measures to increase the competitive position of IWT and to improve the navigability of the Romanian stretch of the Danube between the Iron Gates II and Giurgeni. The approach of the project can be characterized as strategy formulation to create a high capacity transport corridor at minimum investment costs. The project comprises two phases, i.e. River Status Phase and Strategy Development Phase. The first phase of the project has been completed in September 1994 with the submission of the River Status Report, which describes the present status of the Danube river followed by the generation of alternative development strategies for the Danube. In the second project phase selected strategies are analyzed followed by the selection of the preferred river development strategy. This Interim Report for the Strategy Development Phase includes the analyses of the various alternative development strategies. The report will be presented to and discussed with the Romanian authorities to select and further define the preferred development strategy. This preferred strategy will then be further analysed and reported in the Draft Final Report. The main objective of the Danube River Development Strategy project is to improve the navigation conditions of the Romanian section of the Danube between the Iron Gates II (rkm 869) and Giurgeni (rkm 239) in order to create a competitive IWT hinterland connection for the Port of Constantza. Various alternative development strategies have been considered. The strategies are rated on multiple criteria, where it appeared that all considered strategies are economically viable. The alternatives combi-c3 and combi-c4 appeared to have the best results. For description of all the alternatives we refer to the report.Danube River Development Strateg
Synthesis of a traceless-affinity probe to selectively label integrin alpha v beta five in live cells
No full textIntegrin alpha v beta five (ITGαvβ₅) and milk fat globule epidermal growth factor 8 (MFG-E8) are two proteins whose interactions are essential to brain function. Both are highly expressed during periods of brain development when axonal pruning is very active. Recent studies have also shown both ITGαvβ₅ and MFG-E8 to be overexpressed in postmortem brains afflicted with Alzheimer's disease (AD). Despite this strong correlation, our understanding of the underlying mechanisms contributing to synapse elimination in AD is hindered by the lack of chemical tools to study them. Indeed, current chemical tools prevent visualization of protein interactions under endogenous environments. The development of new chemical tools to study protein interactions under endogenous environments without affecting function of both ITGαvβ₅ and MFG-E8 will provide a better understanding of their role in AD’s. This thesis details the synthesis of a fluorescent traceless-affinity probe (TAP) designed to selectively label ITGαvβ₅ to help address this knowledge gap. The fluorescent TAP consists of three smaller molecular components: a ITGαvβ₅ ligand, a cleavable electrophile linker and fluorescent reporter tag. The ITGαvβ₅ ligand and the cleavable electrophile linker were all individually synthesized and then coupled together with the fluorescent tag to assemble the TAP.
Chapter 2 of this thesis focuses on the synthesis of a modified cilengitide allowing for late-stage derivatization at the meta position of the D-phenylalanine. Chapter 3 reviews precedents of TAPs, synthesis of cleavable electrophiles and linkers, and addresses future directions for the development of TAPs. Lastly chapter 4 concludes with a detailed account of the synthetic steps performed and the challenges faced towards assembling the final desired TAPs.
Overall, the synthesis of a novel probe described in this thesis serves as a versatile probe construct with late-stage modularity towards the development of TAP to selectively target ITGαvβ₅. The synthetic routes established in both chapter 3 and 4 constitute significant progress towards a unique probe in the hopes to label ITGαvβ₅ without perturbing function under endogenous conditions.Science, Irving K. Barber Faculty of (Okanagan)Chemistry, Department of (Okanagan)Graduat
Frederic Chopin – 4 Balladia : raportti konsertin toteutuksesta
No full textThe author made his thesis in a concert form. The concert “Frederic Chopin – Four Ballades” was held on 10.10.2017 at Tampere Music Academy’s Pyynikki Hall. The concert consisted of only Chopin’s music and all the works were performed by the author of the thesis. The program was following: Frederic Chopin – Four Ballades: No.1 in G minor, Op. 23, No.2 in F major, Op. 38, No.3 in A-flat major, Op. 47, and No.4 in F minor, Op. 52. After the Ballades, Frederic Chopin's Mazurka in A minor Op. 17 No.4 was performed as an encore.
The main objective of this thesis was to delve into making a musically interesting and professional concert, which includes the whole cycle of works by one composer. The aim of this written report was to clarify the practicing process and the progress of the concert itself. In the report, the author tells about the composer, introduces the pieces played in the concert more closely, and explain the working process in detail. The ways of practising were gathered by participating in piano master-classes and collecting the advices of many teachers from different countries.
More attention has been paid to author’s own ideas and experience. As sources the author used biographies, general dictionaries, music analyses of composer’s works and different music scores. The poster, program and the video of the concert are found as attachments in the thesis. The results show that the performer and members of the audience were satisfied with the performance and the evaluator’s opinions gave interesting information for the developing process
Glutamate induced morphological response in astrocytoma cells
No full textGrowing evidence indicates that dysregulation of glutamate signaling between neurons and astrocytes leads to the onset and progression of brain tumors (glioma). The aberrant morphology of glioma cells from astrocytic origin (astrocytoma cells) with elongated processes is also emerging as an underlying cause of progression and therapy resistance of gliomas. Whether glutamate dysregulation conducts this atypical morphology of astrocytoma cells has not been explored. Since normal astrocytes respond to glutamate by filopodiagenesis and processes extension, observing aberrantly elongated processes in response to excessive glutamate in astrocytoma cells is conceivable; yet it requires detailed empirical support to make it translatable to therapies. In this dissertation, the role of glutamate receptors and contribution of L-type voltage-gated calcium channels (CaVs) in elongation and directional protrusion of the astrocytoma cell processes toward glutamate were investigated.
Protrusion of cellular processes toward glutamate and an intracellular calcium rise were observed in U118-MG astrocytoma cells. α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), whose role in neuro-gliomal interactions has been reported, did not trigger filopodiagenesis in these cells. In contrast, use of selective agonists (kainate and phenyl-kainate) and an antagonist (CNQX) indicated that kainate receptors (KARs) contribute to the glutamate-induced morphological response. However, precisely releasing a KAR caged-agonist (DECM-PhKA) to the 3D-cultured cells showed that despite their role in processes extension, KARs do not contribute to the pathfinding and the directional motility towards glutamate.
CaVs were also found to play a role in the glutamate-induced morphological response in U118-MG cells by using selective antagonists (nifedipine, verapamil and diltiazem). Interestingly, a real-time imaging probe (FluoBar1) revealed that the membranar density of CaV1.2 rises immediately upon exposure to glutamate. Results from application of selective ligands (gabapentinoids and antibody) suggested that an auxiliary subunit of CaVs, α2δ1, links glutamate sensing to the intracellular calcium rise and filopodiagenesis. Strong evidence for the role of α2δ1 was found in heterologous expression systems that acquired the ability to respond to glutamate upon transfection. Altogether, determining the involvement of ligand-gated KARs and voltage-gated CaVs for the first time in the morphology of astrocytoma cells paves the way for therapeutical purposes to prevent progression and malignancy of gliomas.Science, Faculty ofScience, Irving K. Barber Faculty of (Okanagan)Graduat
Development of an affinity-guided probe with turn-on fluorescence to selectively label kainate receptors
No full textKainate receptors (KARs) are classified as one of three main subfamilies of ionotropic glutamate receptors (iGluRs) located in the brain. They have been shown to participate in neurological homeostasis and normal brain development processes such as synapse elimination; however, excessive synapse elimination is a hallmark of neurodegenerative diseases. Despite a strong association between KARs and neurodegeneration, our understanding of the underlying mechanisms that contribute to excessive synapse elimination is hindered by the lack of chemical tools required to study them. The development of new chemical tools to study KARs will provide a better understanding of their role in neurodegenerative processes and help identify therapeutics to treat related symptoms and diseases. This thesis details the synthesis of a fluorescent kainate probe that selectively labels KARs to address this knowledge gap. The kainate probe consists of three smaller molecules; a kainoid ligand, a linker, and a squaraine fluorophore which were all individually synthesized and then coupled to assemble the probe. Chapter 1 provides a brief introduction to kainate receptors and their role in the brain, as well as an overview of fluorescent protein imaging methods and the concept of turn-on fluorescence. Chapter 2 reviews the structural features that are essential to designing kainoid ligands, precedents in the kainoid syntheses, and the synthesis of a novel kainoid analog, (4R)-4-azidokainic acid, to enable late-stage derivatization at the C4 position of kainic acid. Chapter 3 contextualizes the biological applications of squaraine dyes and how they can be utilized to achieve turn-on fluorescence with improved contrast during fluorescent imaging. Next, it describes the syntheses of squaraine and aminosquaraine intermediates, along with an alkyne linker. Chapter 3 concludes with a detailed account of the synthetic steps performed and the challenges faced towards assembling the kainate probe. Overall, the synthesis of a novel kainoid analog, (4R)-4-azidokainic acid, serves as a versatile kainoid intermediate, with late-stage modularity, for the development of new kainate probes. The synthetic routes established in Chapter 3 constitute significant progress towards a unique kainate probe with selective turn-on fluorescence to study kainate receptors.Science, Irving K. Barber Faculty of (Okanagan)Chemistry, Department of (Okanagan)Graduat
Design and expression of an ankyrin-like molecular probe for alpha-neurexin 1 labelling in live neurons
No full textNeurexins (NRXNs) are a set of cell adhesion proteins that play a key role in the formation of new synaptic connections and pre-synaptic differentiation in the brain. NRXNs also participate in the remodeling of synapses terminals. Impairment of proper neurexin function can lead to psychological and developmental disorders, with recent evidence suggesting that they play a role in Alzheimer’s disease. Understanding the molecular mechanisms underlying neurexins alterations is paramount to shed light on their role in neurodegeneration. Current approaches to study NRXN’s function suffer from several limitations. In this project, we developed a molecular probe selective for α-neurexin 1 to label it in live cells by exploiting a neurotoxin found in the venom of Latrodectus spiders.
First, we used a bioinformatics approach to identify the sequence of amino acids within a latrotoxin that binds to α-neurexin 1. This minimal sequence was used to design a peptide scaffold for our molecular probe. Then we generated two distinct expression vectors using molecular biology to express a recombinant sequence for selective probes and isolated them from a bacterial expression system. Finally, we assessed the selectivity and cytotoxicity of our recombinant probes in live cells containing α-NRXN 1.
Overall, advancements were made on the development and activity assessment of novel approaches to study neurexins. Chapter 2 proposed a novel recognition sequence of latrotoxins to neurexin that up to date has not been identified. In chapter 3 we created modular expression plasmids enabling purification with metal chromatography to obtain a recombinant probe for neurexin. Finally, we showed that probe lost cytotoxic activity, but selectivity to neurexin still needs to be further assessed.Science, Irving K. Barber Faculty of (Okanagan)Chemistry, Department of (Okanagan)Graduat
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