Dy3+‐Doped Selenide Chalcogenide Glasses: Influence of Dy3+ Dopant‐Additive and Containment

This work reports on process‐induced impurities in rare‐earth ion: Dy³⁺‐doped selenide chalcogenide glasses, which are significant materials for active photonic devices in the mid‐infrared region. In particular, the effect of contamination from the silica glass ampoule containment used in chalcogenide glass synthesis is studied. Heat‐treating Dy‐foil‐only, and DyCl₃‐only, separately, within evacuated silica glass ampoules gives direct evidence of silica ampoule corrosion by the rare‐earth additives. The presence of [Ga₂Se₃] associated with [Dy] on the silica glass ampoule that has been contact with the chalcogenide glass during glass melting, is reported for the first time. Studies of 0–3000 ppmw Dy³⁺‐doped Ge_16.5As₉Ga₁₀Se_64.5 glasses show that Dy‐foil is better than DyCl₃ as the Dy³⁺ additive in Ge‐As‐Ga‐Se glass in aspects of avoiding bulk crystallization, improving glass surface quality and lowering optical loss. However, some limited Dy/Si/O related contamination is observed on the surfaces of Dy‐foil‐doped chalcogenide glasses, as found for DyCl₃‐doped chalcogenide glasses, reported in our previous work. The surface contamination indicates the production of Dy₂O₃ and/or [≡Si‐O‐Dy=]‐containing particles during chalcogenide glass melting, which are potential light‐scattering centers in chalcogenide bulk glass and heterogeneous nucleation agents for α‐Ga₂Se₃ crystals.     

Regulatory T cells in the control of autoimmunity: the essential role of transforming growth factor beta and interleukin 4 in the prevention of autoimmune thyroiditis in rats by peripheral CD4(+)CD45RC- cells and CD4(+)CD8(-) thymocytes

Previous studies have shown that induction of autoimmune diabetes by adult thymectomy and split dose irradiation of PVG.RT1(u) rats can be prevented by their reconstitution with peripheral CD4(+)CD45RC-TCR-alpha/beta+RT6(+) cells and CD4(+)CD8(-) thymocytes from normal syngeneic donors. These data provide evidence for the role of regulatory T cells in the prevention of a tissue-specific autoimmune disease but the mode of action of these cells has not been reported previously. In this study, autoimmune thyroiditis was induced in PVG.RT1(c) rats using a similar protocol of thymectomy and irradiation. Although a cell-mediated mechanism has been implicated in the pathogenesis of diabetes in PVG.RT1(u) rats, development of thyroiditis is independent of CD8(+) T cells and is characterized by high titers of immunoglobulin (Ig)G1 antithyroglobulin antibodies, indicating a major humoral component in the pathogenesis of disease. As with autoimmune diabetes in PVG. RT1(u) rats, development of thyroiditis was prevented by the transfer of CD4(+)CD45RC- and CD4(+)CD8(-) thymocytes from normal donors but not by CD4(+)CD45RC+ peripheral T cells. We now show that transforming growth factor (TGF)-beta and interleukin (IL)-4 both play essential roles in the mechanism of this protection since administration of monoclonal antibodies that block the biological activity of either of these cytokines abrogates the protective effect of the donor cells in the recipient rats. The prevention of both diabetes and thyroiditis by CD4(+)CD45RC- peripheral cells and CD4(+)CD8(-) thymocytes therefore does not support the view that the mechanism of regulation involves a switch from a T helper cell type 1 (Th1) to a Th2-like response, but rather relies upon a specific suppression of the autoimmune responses involving TGF-beta and IL-4. The observation that the same two cytokines were implicated in the protective mechanism, whether thymocytes or peripheral cells were used to prevent autoimmunity, strongly suggests that the regulatory cells from both sources act in the same way and that the thymocytes are programmed in the periphery for their protective role. The implications of this result with respect to immunological homeostasis are discussed.     

A placebo-controlled study of liposome-mediated gene transfer to the nasal epithelium of patients with cystic fibrosis

The crystal structure of bovine neurophysin-II in its liganded state (Chen et al. [1991] Proc. Natl. Acad. Sci. USA 88, 4240-4244) indicates that the 1-6 sequence has a disordered conformation, lacks noncovalent contacts to other regions of the protein and is distant from the monomer-monomer interface. Cleavage of the 1-6 sequence by Staphylococcus protease V8 yielded a protein that, for the first time, crystallized in both liganded and unliganded states. Insights into the role of the 1-6 sequence in the unliganded state were obtained by NMR and related biophysical comparisons of the native and des-1-6 proteins. NMR spectra demonstrated that the environment and/or conformation of residues in the 1-6 sequence differed in liganded and unliganded states. Additionally, the unliganded des-1-6 protein exhibited a dimerization constant four to five times that of the native protein, potentially accounting for the observation that its peptide affinity was also increased. NMR studies further indicated that the increased dimerization constant of the des-1-6 protein correlated with the presence in the native protein of two isoenergetic forms of the monomer, in contrast to only a single form in the des-1-6 protein, as evidenced by signals from an internal dimerization-sensitive alpha-proton. Thus, the 1-6 sequence reduces the dimerization constant by stabilization of an alternative monomer conformation. A second product of Staphylococcus protease V8 digestion of the native protein was identified as the des-1-6 protein with an internal clip after binding site residue Glu-47, the clip presumably breaking the short 3,10 helix that most directly connects the interface to the interface to the binding site. This product, although unable to bind peptide, retained the dimerization constant of the des-1-6 protein, suggesting a lack of importance of the helix in dimerization and contrasting with the effects of the 1-6 sequence. A model is proposed in which the 1-6 sequence stabilizes the second conformation of the unliganded monomer via interactions affecting the loop region that separates the two neurophysin domains and which has been shown to influence neurophysin self-association.     

Co‐Extrusion of Multilayer Glass Fiber‐Optic Preforms: Prediction of Layer Dimensions in the Extrudate

A three‐dimensional, incompressible and noncavitating model of a glass‐stack coextrusion process, under isothermal and non‐isothermal conditions is numerically simulated by means of computational fluid dynamics. A dynamic mesh approach is taken in a domain‐subdomain type setup to simulate the transient steps in the steady‐velocity phase of the experimental co‐extrusion. The multiphase setup consists of a glass‐stack which is composed of different glass compositions. Experimentally measured glass properties, such as the temperature coefficient of the viscosity of the supercooled glass melts are used to define the flow behavior of the glasses in the starting stack when extruded. The modeled extrudate is numerically verified for transient and spatial errors, leading to the choice of a suitable mesh. Excellent agreement is found between modeling and experiment when plotting the core/cladding dimensions of a step‐index extruded fiber‐optic preform along the length of the preform. This approach can identify the stable part of the preform, in terms of constant core/cladding layer geometry, obviating costly and time‐consuming experimental iteration. Also, the modeling allows prediction of the starting glass‐stack dimensions for a specified fiber design.     

Excretion and metabolism of tipredane, a novel glucocorticoid, in the rat, mouse, monkey, and human

The excretion and metabolism of [3H]tipredane, a novel glucocorticoid, has been studied in mice, rats, marmosets, rhesus and cynomolgus monkeys, and humans. After oral administration, [3H]tipredane was rapidly absorbed, metabolized, and excreted into urine and feces. In mice and male rats, radioactivity was excreted primarily into feces or bile, whereas in female rats, monkeys, and humans, excretion was mainly via the renal route. Some sex differences in the proportions excreted into urine and feces were noted in rodents, with females eliminating relatively more radioactivity in urine. Tipredane was shown to be extensively metabolized, but the routes were highly species-dependent and, in the rat, they were sex-dependent. Unchanged tipredane was not detected in any urine, bile, or blood extracts. Urinary and blood extract profiles indicated that there were between 10 and 30 metabolites in rats and mice, the majority of which constituted < 2% of the dose. In these species, the major pathways involved loss of the thioethyl moiety, S-oxidation of the thiomethyl group, and saturation of the adjacent saturated C16-17 bond. Hydroxylation of the steroid B-ring was seen in the 7 alpha-position in mice and female rats, and in the 6 beta-position in male rats. Metabolism of tipredane in rhesus and cynomolgus monkeys and humans was similar, but less extensive and different to that seen in rodents. The major products, the 6 beta-hydroxylated sulfoxide and sulfone metabolites of tipredane, accounted for 21-36% of the dose in human and monkey urine, and were also major components in blood. In contrast to mice and rats, S-oxidation and an unsaturated C16-17 bond were evident in primates. Metabolism of tipredane was rapid and complex, with significant species differences, although the disposition in rhesus and cynomolgus monkeys seemed to be similar to humans.     

Organochlorine levels in maternal and umbilical cord blood plasma in Arctic Canada

A baseline for exposure to organochlorine and metal contaminants has been established for mothers and newborns in the Northwest Territories and Nunavut areas of Arctic Canada. Maternal and umbilical cord blood plasma organochlorine levels are described for Inuit, Dene, Métis, Caucasian and Other non-Aboriginal participants. Overall, 523 women volunteered to participate by giving their written informed consent between May 1994 and June 1999, resulting in the collection of 386 maternal blood samples, 407 cord blood samples and 351 maternal/cord pairs. Nearly half of all the participants regularly smoked cigarettes, including 77% of the Inuit participants. Maternal and cord results are presented for PCBs (as Aroclor 1260 and 14 congeners) and organochlorine pesticides, including p,p'-DDT, p,p'-DDE, beta-hexachlorocyclohexane (beta-HCH), hexachlorobenzene (HCB), cis and trans nonachlor, heptachlor epoxide, oxychlordane, mirex, dieldrin and toxaphene. Maternal PCB levels (as Aroclor 1260) averaged 4.42 (+/-9.03) microg/l in Inuit, which was 3.3 times higher than those found in Dene/Métis, and 3.4 times higher than levels in Caucasians. Mean DDE levels were 2.8 times higher in the Other non-Aboriginal group (Chinese, Filipino, East Indian and multiple ethnicity) than in the Inuit group, at 3.99 microg/l and 1.42 microg/l, respectively. Cord blood PCB levels (as Aroclor 1260) averaged 1.16 (+/-2.42) microg/l for Inuit participants, which was 3.3-4 fold higher than the other ethnic groups. PCBs, p,p'-DDE and hexachlorobenzene were detected in all maternal samples, and p,p'-DDE was detected in all cord samples. Regression coefficients for maternal/cord pairs are presented for selected organochlorines. Other results from this study, including maternal and cord metals data, will be presented elsewhere.     

Crystallization in 70Ga2S3.30La2S3(mol%) Glasses as a Function of Oxide/Hydroxide Concentration

The crystallization of 70Ga₂S₃^.30La₂S₃(mol%) glasses has been studied using X-ray diffraction and transmission electron microscopy. Two of the glasses were prepared from raw materials with nominally different oxide concentrations. The third was prepared from raw materials aged in an oxygen-depleted, argon-flushed glove box for more than 1 yr. Their oxide/hydroxide impurity content was qualitatively ranked using Fourier transform infrared spectroscopy. The lowest oxide content composition (≤0.5 wt%, supplied information) devitrified readily close to the glass transition temperature, T _g, forming crystallites of a new (GLS) phase with a monoclinic Bravais lattice and a lathlike internal structure. Ga₂S₃was observed in small quantities between the laths. Samples prepared from nonaged, high oxide (1–3 wt%) content precursors produced the most stable glass. On crystallization, these samples exhibited spherulites composed of intergrown laths of melilite-structured La_3.33Ga₆S₁₄and the new monoclinic GLS phase. Whiskers of Ga₂S₃were found in the residual glass between crystallites. Samples prepared from aged raw materials produced spherulites of La_3.33Ga₆S₁₄on crystallization with no identifiable regions of the new GLS phase.