Soft Lewis acid catalyzed cycloisomerization of oxo-alkynes and enynes

In the literature, some transition metal salts have been used as soft Lewis acids to activate alkynes toward nucleophilic attack. For example, Pt(II), Au(I) and Pd(II) catalysts can catalyze cycloisomerization reactions of alkynyl compounds to give a variety of cyclic products. In order to expand the scope of these reactions, in chapter 2 of this dissertation, several alkynyl epoxides were isomerized to cyclic allyl vinyl ethers using PtCl2 as the catalyst. Three of these allyl vinyl ethers were hydrolyzed to 2-hydroxymorpholine derivatives and two were converted to piperidine derivatives by thermal Claisen rearrangement. In order to find more benign and inexpensive catalysts for these types of reactions, in chapter 3 of this dissertation, BiCl3 was used to catalyze the isomerization of eight enynes to pyrrolidine derivatives. This reaction was normally catalyzed by expensive noble metal catalysts, such as Pd(II), Pt(II) and Au(I). All the cyclic products are valuable intermediates in the synthesis of bioactive molecules, these soft Lewis acid catalyzed cycloisomerization may find applications in the synthesis of bioactive molecules.

Multimembership and Identity in Writing Centers and in Industry: Examining the Work of Reconciliation in the Michigan Tech Multiliteracies Center and at Kimberly-Clark Corporation

Writing center scholarship and practice have approached how issues of identity influence communication but have not fully considered ways of making identity a key feature of writing center research or practice. This dissertation suggests a new way to view identity -- through an experience of "multimembership" or the consideration that each identity is constructed based on the numerous community memberships that make up that identity. Etienne Wenger (1998) proposes that a fully formed identity is ultimately impossible, but it is through the work of reconciling memberships that important individual and community transformations can occur. Since Wenger also argues that reconciliation "is the most significant challenge" for those moving into new communities of practice (or, "engage in a process of collective learning in a shared domain of human endeavor" (4)), yet this challenge often remains tacit, this dissertation examines and makes explicit how this important work is done at two different research sites - a university writing center (the Michigan Tech Multiliteracies Center) and at a multinational corporation (Kimberly-Clark Corporation). Drawing extensively on qualitative ethnographic methods including interview transcriptions, observations, and case studies, as well as work from scholars in writing center studies (Grimm, Denney, Severino), literacy studies (New London Group, Street, Gee), composition (Horner and Trimbur, Canagarajah, Lu), rhetoric (Crowley), and identity studies (Anzaldua, Pratt), I argue that, based on evidence from the two sites, writing centers need to educate tutors to not only take identity into consideration, but to also make individuals' reconciliation work more visible, as it will continue once students and tutors leave the university. Further, as my research at the Michigan Tech Multiliteracies Center and Kimberly-Clark will show, communities can (and should) change their practices in ways that account for reconciliation work as identity, communication, and learning are inextricably bound up with one another.

Cathepsin D specifically cleaves the chemokines macrophage inflammatory protein-1 alpha, macrophage inflammatory protein-1 beta, and SLC that are expressed in human breast cancer

Cathepsin D (Cath-D) expression in human primary breast cancer has been associated with a poor prognosis. In search of a better understanding of the Cath-D substrates possibly involved in cancer invasiveness and metastasis, we investigated the potential interactions between this protease and chemokines. Here we report that purified Cath-D, as well as culture supernatants from the human breast carcinoma cell lines MCF-7 and T47D, selectively degrade macrophage inflammatory protein (MIP)-1 alpha (CCL3), MIP-1 beta (CCL4), and SLC (CCL21). Proteolysis was totally blocked by the protease inhibitor pepstatin A, and specificity of Cath-D cleavage was demonstrated using a large chemokine panel. Whereas MIP-1 alpha and MIP-1 beta degradation was rapid and complete, cleavage of SLC was slow and not complete. Mass spectrometry analysis showed that Cath-D cleaves the Leu(58) to Trp(59) bond of SLC producing two functionally inactive fragments. Analysis of Cath-D proteolysis of a series of monocyte chemoattractant protein-3/MIP-1 beta hybrids indicated that processing of MIP-1 beta might start by cleaving off amino acids located in the C-terminal domain. In situ hybridization studies revealed MIP-1 alpha, MIP-1 beta, and Cath-D gene expression mainly in the stromal compartment of breast cancers whereas SLC transcripts were found in endothelial cells of capillaries and venules within the neoplastic tissues. Cath-D production in the breast carcinoma cell lines MCF-7 and T47D, as assessed by enzyme-linked immunosorbent assay of culture supernatants and cell lysates, was not affected by stimulation with chemokines such as interleukin-8 (CXCL8), SDF-1 (CXCL12), and SLC. These data suggest that inactivation of chemokines by Cath-D possibly influences regulatory mechanisms in the tumoral extracellular microenvironment that in turn may affect the generation of the antitumoral immune response, the migration of cancer cells, or both processes.

GPR Reflection Profiles of Clark and Commonwealth Glaciers, Dry Valleys, Antarctica

Englacial horizons deeper than 100 m are absent within 100 MHz ground-penetrating radar (GPR) surface profiles we recorded on Clark and Commonwealth Glaciers in the Antarctic Dry Valleys region. Both glaciers show continuous bottom horizons to 280 m, with bottom signal-to-noise ratios near 30 dB. Density horizons should fade below 50 m depth because impermeable ice occurred by 36 m. Folding within Commonwealth Glacier could preclude radar strata beneath about 80 m depth, but there is no significant folding within Clark Glacier. Strong sulfate concentrations and contrasts exist in our shallow ice core. However, it appears that high background concentration levels, and possible decreased concentration contrasts with depth placed their corresponding reflection coefficients at the limit of, or below, our system sensitivity by about 77 m depth. Further verification of this conclusion awaits processing of our deep-core chemistry profiles.

(Table 3) Sedimentation rates of stage 1 and last glacial maximum from different Holes during cruises of RRS Discovery in 1984-1985 and 1987-1988, and RRS James Clark Ross in 1992-1993

Within the Scotia Sea, the axis of the Antarctic Circumpolar Current (ACC) is geographically confined, and sediments therefore contain a record of palaeo-flow speed uncomplicated by ACC axis migration. We outline Holocene and Last Glacial Maximum (LGM) current-controlled sedimentation using data from 3.5-kHz profiles, cores and current meter moorings. Geophysical surveys show areas of erosion and deposition controlled by Neogene basement topography. Deposition occurs in mounded sediment drifts or flatter areas, where 500-1000 m of sediment overlies acoustic basement. 3.5-kHz profiles show parallel, continuous sub-bottom reflectors with highest sedimentation rates in the centre of the drifts, and reflectors converging towards marginal zones of non-deposition. Locally, on the flanks of continental blocks (e.g. South Georgia), downslope processes are dominant. The absence of mudwaves on the sediment drifts may result from the unsteadiness of ACC flow. A core transect from the ACC axis south to the boundary with the Weddell Gyre shows a southward decrease in biogenic content, controlled by the Polar Front and the spring sea-ice edge. Both these features lay farther north at LGM. The cores have been dated by relative abundance of the radiolarian Cycladophora davisiana, and by changes in the biogenic Ba content, a palaeoproductivity indicator. Sedimentation rates range from 3 to 17 cm/ka. The grain size of Holocene sediments shows a coarsening trend from south to north, consistent with strongest bottom-current flow near the ACC axis, though interpretation is complicated by the presence of biogenic grains. Year-long current meter records indicate mean speeds from 7 cm/s in the south to 12 cm/s in the north, with benthic storm frequency increasing northwards. LGM sediments are predominantly terrigenous and show a clearer northward-coarsening trend, with well-sorted silts in the northern Scotia Sea. Assuming a constant terrigenous source, this implies stronger ACC flow at the LGM, contrasting with weaker Weddell Gyre flow deduced from earlier work.