Ordered intermetallic alloys: an assessment

The paper summarizes our present understanding, as established at a recent workshop, of two classes of intermetallic alloys: nickel and iron aluminides, which are currently used by industries; and advanced intermetallic alloys including silicides and Laves-phase alloys, which have a great potential to be developed as new high-temperature structural materials for future industrial use. The workshop emphasized close interaction and co-operation between basic research, applied research, and industrial development, and stressed discussion of critical scientific and technological issues. The current status of these intermetallic alloys was assessed, and the directions for future research and development, as well as emerging opportunities, were identified. The information presented in the text is summarized from the presentations at the workshop, and so no references are given to the published literature. However, an extensive bibliography is appended, in which further details may be found.     

Species differences in brain adenosine A1 receptor pharmacology revealed by use of xanthine and pyrazolopyridine based antagonists

1. The pharmacological profile of adenosine A1 receptors in human, guinea-pig, rat and mouse brain membranes was characterized in a radioligand binding assay by use of the receptor selective antagonist, [3H]-8-cyclopentyl-1,3-dipropylxanthine ([3H]-DPCPX). 2. The affinity of [3H]-DPCPX binding sites in rat cortical and hippocampal membranes was similar. Binding site affinity was higher in rat cortical membranes than in membranes prepared from guinea-pig cortex and hippocampus, mouse cortex and human cortex. pKD values (M) were 9.55, 9.44, 8.85, 8.94, 8.67, 9.39 and 8.67, respectively. The binding site density (Bmax) was lower in rat cortical membranes than in guinea-pig or human cortical membranes. 3. The rank order of potency of seven adenosine receptor agonists was identical in each species. With the exception of 5'-N-ethylcarboxamidoadenosine (NECA), agonist affinity was 3.5-26.2 fold higher in rat cortical membranes than in human and guinea-pig brain membranes; affinity in rat and mouse brain membranes was similar. While NECA exhibited 9.3 fold higher affinity in rat compared to human cortical membranes, affinity in other species was comparable. The stable GTP analogue, Gpp(NH)p (100 microM) reduced 2-chloro-N6-cyclopentyladenosine (CCPA) affinity 7-13.9 fold, whereas the affinity of DPCPX was unaffected. 4. The affinity of six xanthine-based adenosine receptor antagonists was 2.2-15.9 fold higher in rat cortical membranes compared with human or guinea-pig membranes. The rank order of potency was species-independent. In contrast, three pyrazolopyridine derivatives, (R)-1-[(E)-3-(2-phenylpyrazolo[1,5-a]pyridin-3-yl) acryloyl]-2-piperidine ethanol (FK453), (R)-1-[(E)-3-(2-phenylpyrazolo[1,5-a]pyridin-3-yl) acryloyl]-piperidin-2-yl acetic acid (FK352) and 6-oxo-3-(2-phenylpyrazolo[1,5-a]pyridin-3-yl)-1(6H)-pyridazinebutyric acid (FK838) exhibited similar affinity in human, guinea-pig, rat and mouse brain membranes. pKi values (M) for [3H]-DPCPX binding sites in human cortical membranes were 9.31, 7.52 and 7.92, respectively. 5. Drug affinity for adenosine A2A receptors was determined in a [3H]-2-[4-(2-carboxyethyl)phenethylamino]-5'-N-ethylcarboxamido ade nosine ([3H]-CGS 21680) binding assay in rat striatal membranes. The pyrazolopyridine derivatives, FK453, FK838 and FK352 exhibited pKi values (M) of 5.90, 5.92 and 4.31, respectively, compared with pKi values of 9.31, 8.18 and 7.57 determined in the [3H]-DPCPX binding assay in rat cortical membranes. These novel pyrazolopyridine derivatives therefore represent high affinity, adenosine A1 receptor selective drugs that, in contrast to xanthine based antagonists, exhibit similar affinity for [3H]-DPCPX binding sites in human, rat, mouse and guinea-pig brain membranes.     

Optical absorption and luminescence in poly(4,4′-diphenylenediphenylvinylene)

Poly(4,4′-diphenylenediphenylvinylene), PDPV, is a soluble conjugated polymer that shows a degree of conjugation similar to that in poly-(paraphenylene). The optical properties of thin films exposed to AsF₅ show the appearance of features below the $\text{π-π}{}^1$ gap at 3 eV that can be interpreted in a model of dopant-induced polaron and bipolaron defects. When excited above the $\text{π-π}{}^1$ gap, PDPV shows a strong luminescence peaked at 2.4 eV. The Stokes' shift of 1 eV can be accounted for by radiative decay from a photogenerated polaron-exciton defect.     

Adaptive decentralized control under non-uniqueness of the optimal control

We study the problem of decentralization of flow control in packet-switching networks under the isarithmic scheme. An incoming packet enters the network only if there are permits available at the entry port when it arrives. The actions of the controllers refer to the routing of permits in the network and the control variables are the corresponding probabilities. We study the behavior of adaptive algorithms implemented at the controllers to update these probabilities and seek optimal performance. This problem can be stated as a routing problem in a closed queueing network. The centralized version of a learning automation is a general framework presented along with the proof of asymptotic optimality. Decentralization of the controller gives rise to non-uniqueness of the optimal control parameters. Non-uniqueness can be exploited to construct asymptotically optimal learning algorithms that exhibit different behavior. We implement two different algorithms for the parallel operation and discuss their differences. Convergence is established using the weak convergence methodology. In addition to our theoretical results, we illustrate the main results using the flow control problem as a model example and verify the predicted behavior of the two proposed algorithms through computer simulations, including an example of tracking.The work of this author was partially supported by a grant from the Canadian Institute for Telecommunications Research under the NCE program of the Government of Canada, and partially supported by NSERC grant WFA 0139015 and FCAR-Québec grant 95-NC-1375.The work of this author was supported by a grant from the CITR under the NCE program of the Government of Canada.     

Medial prefrontal lesion deficits involving or sparing the prelimbic area in the rat

OBJECTIVE: Evaluate wound healing of incisions created by the scalpel, electrocautery, CO2 laser, and potassium titanyl phosphate (KTP) laser in the upper aerodigestive tract in an animal model. STUDY DESIGN: Prospective randomized study in an animal model. METHODS: Postoperative oral intake, histologic depth of injury, and tensile mechanical strength were measured in rat tongues after creating incisions using a scalpel, electrocautery, CO2 laser, and KTP laser. An unpaired, two-tailed Student's t-test was used to compare results between the experimental groups. RESULTS: Oral intake, indirectly assessed by postoperative weight loss, by the third postoperative day was significantly decreased in the electrocautery (P = 0.004), CO2 laser (P = 0.001), and KTP laser (P = 0.0001) groups as compared with the scalpel group. The depth of the wound healing, as assessed by histologic examination, was successively greater for the scalpel (75 +/- 13 microm), electrocautery (110 +/- 10 microm), CO2 laser (145 +/- 10 microm), and KTP laser (195 +/- 23 microm) groups. However, this difference was only statistically significant for the CO2 laser (P = 0.006) and KTP laser (P = 0.01) groups relative to the scalpel group. Wounds created by the KTP laser had the lowest strength (76.5 +/- 6.9 kPa) as compared with the CO2 laser (156 +/- 28.4 kPa), electrocautery (153 +/- 15.7 kPa), and scalpel groups (249 +/- 61.8 kPa). This difference was only statistically significant for the KTP laser group (P = 0.02) when compared with the scalpel group. CONCLUSIONS: Wounds created in the upper aerodigestive tract of rats by scalpels result in the least postoperative weight loss, tissue destruction, and decrease in tensile strength, whereas wounds created by the KTP laser demonstrated a significantly greater postoperative weight loss, depth of wounding, and decrease in tensile strength.     

Relationships between cell density, glutathione and proliferation of A549 human lung adenocarcinoma cells treated with acrolein

Acrolein is a highly electrophilic alpha,beta-unsaturated aldehyde to which humans are exposed in various situations. Acrolein reacts rapidly with and depletes cellular glutathione (GSH), and is toxic to various types of cells. In the current study, the ability of acrolein to alter proliferation of A549 cells was found to be dependent on cell density as well as total cell number. Thus, 'doses' must be expressed per cell rather than as a concentration, and all related studies need to be performed by plating a constant number of cells. A549 cells were plated at various densities and treated with acrolein after 48 h. Acrolein doses up to 47 fmol/cell at the time of treatment did not cause cell lethality. However, growth of A549 cells (as shown by thymidine incorporation, alamarBlue and total protein) was inhibited at acrolein levels > 34 fmol/cell in 6-well plates seeded at 5000 cells/cm2 48 h prior to treatment. Cellular GSH levels were decreased 34% by 2 h at acrolein levels of 6.7 fmol/cell and by 65% at 47 fmol/cell. Recovery of GSH was rapid at 6.7-47 fmol/cell acrolein, returning to control levels or above by 12 h post-treatment. These data show a strong correlation between cellular GSH and proliferation. The apparent conflict with a previous study of Ramu et al., suggesting that sublethal concentrations (up to 10 microM) of acrolein inhibited the proliferation of A549 cells without a decline in total cellular GSH, arose because, while the acrolein concentration was the same in cells used for proliferation and GSH assays, GSH measurements were done in cells plated at a higher density, resulting in a much lower acrolein dose per cell. Interestingly, very low dose levels of acrolein with cells seeded at low densities stimulated cell growth despite an initial decline in GSH content. Preliminary studies with the stress genes hsp70 and gadd153 suggest that acrolein at 35 fmol/cell does not stimulate formation of their mRNA beyond the level stimulated by a 2 h incubation in serum-free medium but may actually delay or decrease the induced expression. The mechanism(s) of the inhibitory and mitogenic effects of acrolein remains to be determined, but could be due to changes in gene expression induced by this electrophile, perhaps mediated by changes in GSH.     

Reoperation for recurrent coronary artery disease: results of 200 consecutive cases

OBJECTIVE: To quantify first-pass enhancement of cervix carcinoma using fast dynamic MRI. To assess the accuracy of dynamic contrast-enhanced colour-coded MRI for determining tumour invasion into surrounding pelvic tissues. METHODS: Gadolinium enhanced dynamic MRI at one image every 2 s was performed in 47 patients with cervical carcinoma and five controls. First-pass contrast enhancement of cervix carcinoma and surrounding pelvic tissues was quantified. Automated colour-coded images were constructed using the dynamic parameters slope, amplitude and timing of enhancement. Of 47 patients, 28 underwent surgery and colour coded images were correlated with histological findings. RESULTS: First-pass contrast enhancement imaging of cervix carcinoma required a temporal resolution of dynamic MRI of one image every 3-4 s. Cervix carcinoma first-pass was more rapid and intense than that of other pelvic tissues (P<0.001) with the exception of normal myometrium (P>0.05). Binary colour coding, however, was not reliable for tumour delineation or for accurate assessment of tumour invasion into the parametria or the bladder wall. Overestimation of the extent of tumour invasion occurred in 15, 16 and nine out of 28 patients, respectively, using amplitude, slope and timing of enhancement as parameters. CONCLUSION: Dynamic contrast-enhanced colour-coded MRI of cervix carcinoma has limited value for assessing the extent of tumour spread and tumour staging.     

Structural determinants of calcium signaling by RGD peptides in rat osteoclasts: integrin-dependent and -independent actions

Extensive characterization of the vitronectin receptor (VNR), a member of the integrin group of cell adhesion molecules, which is abundantly expressed in osteoclasts, has revealed a role for this receptor in osteoclast adhesion as well as bone resorption. Earlier evidence from our laboratory suggests that VNR is also capable of transducing intracellular signals following receptor ligand interaction, although this function is poorly understood. Thus, addition of peptides containing the minimal tripeptide Arg-Gly-Asp (RGD) integrin recognition sequence elicits transient increases in intracellular free calcium ions, with maximal responses seen with a bone sialoprotein peptide, BSP-IIA. In the present study we have attempted to determine some of the structural requirements for calcium signaling in osteoclasts using derivatives of the peptide PRGDN/T sequence found in bone sialoprotein. While some peptides, such as the parent sequence PRGDN, can induce both signaling and retractile events, it was found that minor structural modifications yielded peptides such as PRADN which elicited a transient increase in intracellular free calcium ions without promoting a reduction in osteoclast spread area (retraction). Conversely, certain other modifications resulted in peptides, such as PrGDN and benzoyl-RGDN, which effect osteoclast retraction, while having minimal Ca2+ signaling capabilities. Osteoclast adhesion, and hence retraction, are known to be RGD-dependent and integrin-dependent events. However, intracellular Ca2+ signaling is RGD-independent and, based on lack of inhibition by an anti-beta 3 integrin antibody F11 and echistatin, very likely integrin-independent. These data suggest that signaling is not always via VNR and as yet unknown receptors on the osteoclast membrane play a role in osteoclast signaling and hence function.