Heparanase (Hpa1) is an enzyme overexpressed in nearly all cancers, typically at the tumour growth front. It cleaves proteoglycan heparan sulfate (HS) chains to release growth factors necessary for tumour growth. While some carbohydrate-based mimetic inhibitors have progressed to advanced clinical trials, new inhibitors and tools to further investigate heparanase are of continued interest. This thesis proposes a HS mimetic trisaccharide sequence that can bind Hpa1 and is suitable both for biological evaluation and inhibitor development. Synthetic work was then undertaken toward the progression of this moiety. Exploring building blocks applicable to the trisaccharide, conformationally-locked glucose derivatives were developed. This included the introduction of a conformational switch that resulted in the isolation of constrained half-chair conformers. The synthetic work toward trisaccharide formation also evaluated the utility of 1,2-cyclohexane-diacetal as a protecting group with glucuronic acid. The disarming qualities of these moieties were assessed, leading to the development of alternate routes. A more linear approach resulted in the formation of important disaccharide building blocks that contribute toward the synthesis of the core trisaccharide, including isolated 1,2-orthoesters. Further development of the chemistry established herein should allow for the formation of the desired core trisaccharide, while contributions have additionally been made toward its tool functionalisation and use in multivalent schemes.

No description available.

Xu, Yeming = 水熱法和熱蒸法製備硫化鋅納米结构的電子輻射損傷研究 / 徐業明. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2007. / Includes bibliographical references (leaves 61-63). / Text in English; abstracts in English and Chinese. / Xu, Yeming = Shui re fa he re zheng fa zhi bei liu hua xin na mi jie gou de dian zi fu she sun shang yan jiu / Xu Yeming. / Abstract --- p.i / 摘要 --- p.ii / Acknowledgment --- p.iii / List of Figures --- p.VII / Table of contents --- p.XI / Chapter Chapter 1 --- Introduction --- p.1 / Chapter Chapter 2 --- Background of electron beam irradiation --- p.4 / Chapter 2.1 --- Basic principles of electron beam irradiation --- p.4 / Chapter 2.1.1 --- Atomic displacement --- p.5 / Chapter 2.1.2 --- Electron beam sputtering --- p.7 / Chapter 2.1.3 --- Electron beam heating --- p.8 / Chapter 2.1.4 --- Radiolysis --- p.11 / Chapter Chapter 3 --- Instrumentation --- p.13 / Chapter 3.1 --- X-ray photoelectron spectroscopy (XPS) --- p.13 / Chapter 3.1.1 --- Basic principles --- p.13 / Chapter 3.1.2 --- Chemical shifts in x-ray photoelectron spectroscopy --- p.16 / Chapter 3.2 --- The principle of the Scanning Electron Microscopy (SEM) --- p.16 / Chapter 3. 3 --- Transmission Electron Microscope (TEM) --- p.19 / Chapter 3. 3.1 --- Principle of the TEM --- p.19 / Chapter 3.3.2 --- Electron specimen interaction in TEM --- p.21 / Chapter 3.3.3 --- Electron Diffraction --- p.22 / Chapter 3.3.4 --- Contrast --- p.22 / Chapter 3.4 --- Energy dispersive x-ray spectroscopy --- p.23 / Chapter 3.5 --- Elemental mapping using Electron Energy Loss Spectrometer (EELS) --- p.24 / Chapter Chapter 4 --- Structure Degradation of ZnS Nanomaterials Synthesized via Hydrothermal Method --- p.26 / Chapter 4.1 --- Experimental --- p.26 / Chapter 4.2 --- Structure degradation of ZnS nanotubes synthesized via hydrothermal method --- p.27 / Chapter 4.2.1 --- Chemical and structural characterization of the as-synthesized nanotubes --- p.27 / Chapter 4.2.2 --- Crystallinity and structural degradation of the nanosheet under the electron beam irradiation --- p.29 / Chapter 4.2.3 --- Nanotube structure degradation with different experimental parameters --- p.33 / Chapter 4.3 --- Structure degradation of ZnS nanosheets synthesized via hydrothermal method --- p.34 / Chapter 4.3.1 --- Chemical and morphological characteristics of the ZnS nanosheets --- p.34 / Chapter 4.3.2 --- Crystallinity and structural degradation of the nanosheet under the electron beam irradiation --- p.37 / Chapter 4.3.3 --- Nanosheet structure degradation with different experimental parameters --- p.41 / Chapter 4.3.4 --- Discussion on the damage mechanisms --- p.45 / Chapter Chapter 5 --- Structure Degradation of ZnS Nanobelts Synthesized via thermal evaporation Method --- p.48 / Chapter 5.1 --- Experimental --- p.48 / Chapter 5.2 --- Chemical and morphological characteristics of the ZnS nanobelts --- p.49 / Chapter 5.3 --- Crystallinity and structural degradation of the nanobelt under the electron beam irradiation --- p.50 / Chapter 5.4 --- Nanobelt structure degradation with different experimental parameters --- p.55 / Chapter 5.5 --- Discussion on the damage mechanisms --- p.56 / Chapter Chapter 6 --- Conclusion --- p.59 / References --- p.61

Purpose: To assess and measure the compatibility of irreversible hydrocolloids (alginates) readily available in South Africa with available gypsum products by testing the quality reproducibility of lines on a standard die. Method: Under controlled laboratory conditions six brands of alginate impression material were tested against six types of gypsum products using the EN 21563:1991 (ISO 1563:1990) recommended protocol. Photomicrographs of the resultant gypsum surfaces were taken and a scoring method similar to that described by Owen (1986b) was used by previously calibrated independent examiners in order to evaluate the acceptable alginate/gypsum combinations. Results: There was an unexpected variability in the rater scores, and considerable variability in the quality of the casts from the various possible alginate/gypsum combinations. Statistical analysis allowed for the use of combination mean scores taking into account all the scores of all the raters, but discrimination was limited to those combinations with the best scores. The best possible score was 3 and the worst 12. In light of the inter-rater variability the combinations with scores of 4 or less were considered to be the recommended combination for clinical application. No alginate proved to be universally compatible with all the gypsum products tested and no gypsum product was universally compatible with all alginates. Conclusion: This study has highlighted the fact that not all alginates are compatible with all gypsum products, and that it is possible to find appropriate combinations for the clinical requirements of a dental cast. However, the fact that there were nine combinations which scored in the very worst category means that manufacturers of alginates should recommend specific gypsum products with which they are compatible and which were used to obtain their ISO rating, and clinicians should be more aware of the need for compatibility.

Les carbohydrates font partie des trois grandes classes de biopolymères présents dans la nature. Ils représentent 75% de la biomasse. Les glycosaminoglycanes font partie des carbohydrates, ils sont présents à la surface des cellules et sont responsables de la signalisation cellulaire. Ils sont importants dans de nombreux processus biologiques. Vu leur importance en biologie et en santé, il est nécessaire de comprendre leur fonctionnement. Dans cette thèse nous avons étudié deux types de tétrasaccharides de glycosaminoglycanes (chondroïtine sulfate et dermatane sulfate) avec une nouvelle méthode qui couple la spectrométrie de masse à la spectroscopie vibrationnelle (MS/IR). Nous avons montré qu’avec cette méthode la signature de l’empreinte OH fonctionne pour les glycosaminoglycanes qui présentent des groupements Coo- et des groupements sulfate contrairement aux oses simples. Cette méthode a également validé la pertinence du séquençage pour l'élucidation de profils de sulfate et la nature de l’hexuronique dans les oligosaccharides de glycosaminoglycanes. L’approche du séquençage améliore considérablement la résolution structurelle par rapport à la simple analyse spectroscopique de l'ion précurseur. Elle permet d’avoir plus d’information sur les oligosaccharides. Et pour finir nous avons proposé un protocole pour l’analyse de mélanges afin de déterminer le ratio des différents éléments présents dans le mélange / Carbohydrates are among the three major classes of biopolymers found in nature. They represent 75% of the biomass. Glycosaminoglycans are carbohydrates, they are present on the surface of cells and are responsible for cell signaling. They are important in many biological processes. Given their importance in biology and health, it is necessary to understand their mechanism. In this thesis we studied two types of glycosaminoglycan tetrasaccharides (chondroitin sulfate and dermatan sulfate) with a new method that combines mass spectrometry with vibrational spectroscopy (MS / IR). We have shown that with this method the signature of the OH-fingerprint works for glycosaminoglycans which have COO- groups and sulfate groups in contrast to simple carbohydrates. This method also validated the relevance of sequencing for the elucidation of sulfate profiles and the nature of hexuronic in oligosaccharides of glycosaminoglycans. The sequencing approach significantly improves the structural resolution compared to the simple spectroscopic analysis of the precursor ion. It provides more information on oligosaccharides. And finally we proposed a protocol for the analysis of mixtures to determine the ratio of the different elements present in the mixture

Thesis (M.S.)--Brigham Young University. Dept. of Chemical Engineering, 2006. / Includes bibliographical references (p. 75-78).

Thesis (Ph.D.) in Chemical Enigneering--University of Maine, 2006. / Includes vita. Includes bibliographical references (leaves 189-193).

Bottom water hypoxia and its influence on the environment have been topics of increasing concern for many coastal regions. This research addresses both spatial and temporal variability in sediment biogeochemistry at the southeastern region of Corpus Christi Bay, TX, where seasonal (summer) hypoxia occurs. Traditional techniques for determination of a variety of dissolved and solid components, benthic oxygen demand, and sulfate reduction rates were augmented by measurements using solid state microelectrodes to simultaneously determine concentrations of dissolved O2, Mn2+, Fe2+, and [sigma]H2S in multiple small - interval (1 mm) depth profiles of sediment microcosms. Oxygen concentrations in the overlying water were manipulated in the sediment microcosms and electrode depth profile measurements were made over ~ 500 hours of experimentation. Laboratory and field microelectrode results were in good agreement for both norm - oxic and anoxic time periods. Results indicated that iron (Fe2+) and sulfide ([sigma]H2S) were the redox reactive species in these sediments. During hypoxic conditions an upward migration of dissolved Fe2+and [sigma]H2S through the sediment column and, at times, into the overlying water was observed as the dissolved oxygen concentrations decreased. A corresponding decline in the vertical extent of these redox species occurred when the overlying water was re-oxidized. When both dissolved iron and sulfide coexisted, FeS minerals were formed in the sediment, preventing sulfide diffusion into the overlying water. However, after a long duration of hypoxia (> 200 hours) this buffering capacity was exceeded and both iron and sulfide penetrated into the overlying waters. Results indicated that iron may have a greater influence on hypoxia than sulfide because its concentration in the overlying waters during induced hypoxia was an order of magnitude greater than those of sulfide. Moreover, in the southeastern region of the Bay, where mixing was minimal and the water column was shallow, the sediments alone may have caused the onset of the hypoxic event in a relatively short time period (< 5.5 days). These results demonstrated that in shallow marine environments where seasonal hypoxia occurs, such as Corpus Christi Bay, the associated major changes that take place in the sediment biogeochemistry must be included in benthic - pelagic models for overlying water hypoxia.

No description available.

Sulfation of tyrosine residues is a post-translational modification that occurs on many secretory as well as transmembrane proteins. This modification is believed to be essential for numerous biological processes. However, one of the factors hindering the study of the significance of sulfotyrosine (sTyr) within a protein is the absence of a general method that enables the synthesis of sTyr peptides in satisfactory yields and purity. A general approach to the synthesis of sTyr-bearing peptides was developed in which the sTyr residue is incorporated into the peptides with the sulfate group protected. For the implementation of this general approach a new protecting group for sulfates, namely, the dichlorovinyl (DCV) group was developed. This was accomplished by conducting a careful analysis of the reaction of a trichloroethyl (TCE)-protected sulfate ester with piperidine and 2-methylpiperidine (2-MP). A unique sulfuryl imidazolium reagent, compound 2.22, was also developed that enabled the ready synthesis of DCV-protected sulfates. This reagent was used to prepare the amino acid building block FmocTyr(SO3DCV)OH (2.23). An alternative and more economical synthesis of FmocTyr(SO3DCV)OH (2.23) was also developed that did not require reagent 2.22. Fmoc-based solid phase peptide synthesis (SPPS) was used to incorporate 2.23 into peptides using 2-MP for Fmoc removal. After cleavage of the peptide from the support, the DCV group was removed by hydrogenolysis to give sTyr peptides in good yield and purity. Using this approach a variety of sTyr peptides were prepared including a tetrasulfated 20-mer corresponding to residues 14-33 in chemokine receptor D6 and a disulfated 35-mer corresponding to residues 8-42 of the N-terminus region of the chemokine receptor DARC and this is the largest multisulfated sTyr–bearing peptide made to date. It was also demonstrated that the incorporation of an important non-hydrolyzable sTyr analog, 4-(sulfonomethyl)phenylalanine (Smp), into peptides can be accomplished in good yield by protecting the sulfonate residue with a TCE group during SPPS. This approach was shown to be superior to the previously reported method where the sulfonate group is unprotected. Finally, a number of sulfotyrosine bearing peptides were synthesized and tested as protein tyrosine phosphatase-1B (PTP1B) inhibitors