• Refine Query
  • Source
  • Publication year
  • to
  • Language
  • 2174
  • 1005
  • 999
  • 484
  • 3
  • 3
  • 2
  • 2
  • 1
  • 1
  • 1
  • 1
  • 1
  • 1
  • Tagged with
  • 9821
  • 3334
  • 1736
  • 1362
  • 1358
  • 1358
  • 1061
  • 663
  • 516
  • 282
  • 277
  • 269
  • 248
  • 246
  • 232
  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.

Design, synthesis and biological evaluation of small molecules for controlling cellular development

Haffez, Hesham Raffat Shawky January 2016 (has links)
Cellular differentiation is a process directed by a wide range of controlling signaling molecules and pathways. All-trans-retinoic acid (ATRA) is one such compound that shows a wide range of biological activity. The endogenous effects of ATRA have the potential to be translated into many in vitro and in vivo applications; however, its administration is associated with many drawbacks. Consequently, a large group of synthetic analogues known as synthetic retinoids - that are structurally similar to ATRA have been prepared and tested in vitro in the search for higher stability and more potency. A small library of stable synthetic retinoids known as EC and GZ derivatives were prepared and their biological activity investigated using TERA2.cl.SP12 human embryonal carcinoma (EC) stem cells and SHSY5Y neuroblastoma cells. Two compounds, EC23 and GZ25 were found to inhibit cellular proliferation and induce neural differentiation in both cell lines. EC50s showed higher binding affinity of these two analogues to all RAR types and was confirmed by how they fit into the binding pocket of the different RARs. They bind into the binding pocket through a hydrophilic network of carboxylate group with Arg (salt bridge) and Ser (two hydrogen bonds) residues similar to ATRA. These effects were thoroughly characterized and quantified by monitoring the phenotypic changes of both cell lines and the gene expression markers such as RAR-β, PAX6, NeuroD1 which showed higher order of efficacy for induction of neuronal differentiation.In this study, the combined use of calculated chemical structures, molecular docking tools with receptor binding assays and biological characterization was useful to probe, and hence, understand the biological activity of certain synthetic retinoids with the ultimate goal of designing more specific synthetic retinoic acid derivatives.

Ultrafast dynamics of gas phase anions

West, Christopher William January 2016 (has links)
The ultrafast dynamics of a number of molecules have been studied in the gas phase through the use of frequency- angle- and time-resolved photoelecron imaging. A particular emphasis has been applied to the behaviour of biologically relevant molecules following photoexcitation. The gaseous ions were produced from an electrospray ionisation source and interrogated by a purpose-built velocity-map imaging photoelectron spectrometer with a minimum temporal resolution of ~50 fs. Firstly, the details of a global kinetic fitting routine for a time-resolved photoelectron spectrum are presented. Through fitting the constituent photoelectron images to a kinetic fit, the photoelectron angular anisotropy of the constituent features of the time-resolved spectrum is preserved. Secondly, the dynamics of the green fluorescent protein model chromophore following UV excitation were explored, identifying internal conversion of the initially produced excited state population to a lower lying excited state before photodetachment. Thirdly, frequency- and angle-resolved photoelectron imaging is employed to investigate the dynamics of anionic resonances of para-benzoquinone, that have been implicated in facilitating electron attachment to this moiety. Fourthly, the photoelectron spectra of a series of carboxylic acids are presented in order to assess the feasibility of producing anions by attaching carboxylic acids to neutral chromophores. Fifthly, a time-resolved photoelectron spectrum of the biological chromophore and carboxylic acid, all-trans¬-retinoic acid is presented. Finally, highly anisotropic photoelectron spectra of the dianion, antimony tartrate are presented. In order to explain the anisotropy, classical trajectories of electrons on the molecular electrostatic potential energy surface are calculated. From this, the observed anisotropy can be assigned the the shape of the molecular repulsive Coulomb barrier.

Some studies on boronium salts (I) ; The coordination chemistry of beryllium borohydride (II)

Banford, L. January 1965 (has links)
No description available.

Molecular imaging probes for N-methyl-D-aspartate receptors

Sim, Neil January 2014 (has links)
The non-invasive detection of neuronal transmission is of prime importance in order to understand brain function better. This will aid cognitive neuroscience, as well as medical science, in the early detection of diseased states. Herein, approaches to molecular imaging of the NMDA receptor, a receptor subtype of the excitatory neurotransmitter glutamate, through the use of targeted contrast agents, is described. Initially, a series of NMDA receptor-targeted MRI contrast agents was developed based upon a known competitive NMDA receptor antagonist, appended to an N-linked ‘Gd-DOTA’ core that possesses a fast-exchanging water molecule. Their use as responsive MR imaging probes was evaluated in vitro using a neuronal cell line model, and three contrast agents showed large enhancements in cellular relaxation rates. In order to confirm NMDA receptor localisation, derivatives of the lead compounds were also prepared. The derivatives contained a biotin moiety, which allowed direct visualisation of the cell-surface receptors, after addition of an AvidinAlexaFluor®-488 conjugate. Using these derivatives, the specificity and reversibility (in the presence of glutamate) of binding at the NMDA receptor was demonstrated in living cells using laser scanning confocal microscopy. In an attempt to generate a single-component NMDA receptor-targeted optical imaging agent, a very bright europium complex conjugated to an NMDA receptor-binding moiety was synthesised. Unfortunately, upon incubation with a neuronal cell line model, complex localisation appeared to be dictated by the ligand structure and not by the receptor-binding moiety. One emerging imaging technique with potential applications in neuronal imaging is photoacoustic imaging. Two NMDA receptor-targeted photoacoustic imaging agents were synthesised and their ability to label NMDA receptors assessed in vitro. Finally, preliminary in vivo evaluation of the most promising photoacoustic imaging agent is described.

The diverse roles of the Pseudomonas aeruginosa phospholipase PlcH and the Toxoplasma gondii serine palmitoyltransferase in sphingolipid biochemistry

Thye, Julie Kristine January 2014 (has links)
Sphingolipids are essential for cell survival for almost all eukaryotic cells. Due to the large variety in sphingolipid structure, they possess a wide range of functions from acting as structural components of membranes to participating in cell signalling pathways. Sphingolipid metabolism and catabolism can occur via numerous routes and the disruption of sphingolipids or sphingolipid biosynthetic pathways is therefore detrimental to cells. The vast majority of prokaryotes do not utilise sphingolipids, however certain prokaryotic enzymes which posses similar functionality to those involved in sphingolipid biosynthesis, are crucial to pathogen-host interactions. For instance, the opportunistic human pathogen, Pseudomonas aeruginosa, which represents a particular threat to cystic fibrosis patients, expresses a variety of virulence factors. One of these, the heterodimeric complex, PlcHR₂, is a phospholipase C. It also possesses sphingomyelinase properties which has been suggested to be responsible for the highly specific cytotoxic effects of the enzyme. The first aim of the thesis was to express and purify the PlcH part of the complex in order to functionally and biophysically characterise it, laying the foundation towards the crystal structure determination. Furthermore, the sphingomyelinase activity assay was established, utilising PlcHR₂, in order to screen several commercially available compounds and an in-house library of ceramide analogues for potential inhibitory effect on the enzyme. Five inhibitory and five activating compounds were identified. Sphingolipids also play crucial roles in more complex human pathogens, including the apicomplexan protozoan parasite, Toxoplasma gondii, which causes a life-threatening disease, toxoplasmosis, in animals and humans. The first step in the sphingolipid biosynthetic pathway is catalysed by serine palmitoyltransferase (SPT), making it an important drug target in several parasites as preventing this step from occurring in the biosynthesis will result in an incapability of the parasite to proliferate. Several constructs of the SPT from T. gondii were designed in order to establish the smallest catalytically active domain. The constructs were expressed and purified in order to characterise the enzyme by a range of biochemical and biophysical methods, with the ultimate aim of obtaining a crystal structure for the enzyme. The final part of the thesis focussed on the crystallisation and crystal structure determination of a triosephosphate isomerase (TPI) from a hyperthermophilic archaeon, Sulfolobus solfataricus. The TPI protein assumes a β α₈-barrel fold, the most common protein fold. It is thus an ideal target to study to gain an understanding of the evolutionary process that enzymes undergo to stabilise their structure and function at the extreme conditions they are subjected to in extremophiles.

An investigation of chlorofluorocyclohexanes (a) ; The action of chlorine trifluoride on trichloroacetic acid (b)

Cuthbertson, F. January 1957 (has links)
No description available.

The telomerisation and polymerisation of fluoro-olefins

Plimmer, Peter N. January 1962 (has links)
No description available.

Some fluorinated ethers and esters (Part I) ; Mass spectrometric studies on halogenated aromatic compounds (Part II)

Eastwood, Frank George January 1969 (has links)
No description available.

Reactions of the diazocyanides (Part I) ; The preparation of cinnoline derivatives (Part II)

Stephenson, Oliver January 1940 (has links)
No description available.

The iodous sulphates

Argument, Cyril January 1944 (has links)
No description available.

Page generated in 0.0408 seconds