Inhibition of feline collateral vessel development following experimental thrombolic occlusion

We compared development of feline hindlimb collateral circulation after acute occlusion of the terminal aorta by ligation, thrombus formation, and formation of a "closed" aortic loop containing thromboplastin. Collateral circulation development was assessed by aortograms, scintillation scans, neurological signs following occlusion, measurement of hindlimb muscle blood flow, and forelimb and hindlimb temperature. In cats in which aortic occlusion was the result of ligation or thromboplastin in the aortic loop, paralysis was not evident. Aortograms and scintillation scans indicated hindlimb blood flow. Both muscle temperature and blood flow data indicated that the return of blood flow was rapid. The 5th lumbar artery appears to be the origin of the collateral vessels. The mid-zone component is a dorsal and ventral vertebral route and an epaxial muscle route. The reentry components are the 6th or 7th lumbar arteries. The collateral vessels arise from preexisting collateral vessels. Of those cats in which aortic occlusion was the result of a thrombus, all exhibited paralysis. Aortograms, scintillation scans, muscle temperature, and hindlimb blood flow data indicated reduced hindlimb blood flow. The results suggest that the thrombus has an inhibitory effect on the development of collateral circulation.     

Features of autoimmune hepatitis in primary sclerosing cholangitis: an evaluation of 114 primary sclerosing cholangitis patients according to a scoring system for the diagnosis of autoimmune hepatitis

Overlapping features between primary sclerosing cholangitis (PSC and autoimmune hepatitis (AIH) have previously been noted. To assess systematically similarities between these disorders, we have evaluated 114 PSC patients (36 women; 78 men), all confirmed by endoscopic retrograde cholangiography (ERC), according to a scoring system proposed by The International Autoimmune Hepatitis Group for the diagnosis of AIH. The scoring system attributes positive or negative scores to the parameters sex, ratio of elevation of serum levels of alkaline phosphatase (ALP) vs. aminotransferase, serum levels of immunoglobulins and autoantibodies, viral markers, history of drug and alcohol intake, genetic factors, liver histology, and response to therapy. Two of the PSC patients (2%) obtained scores above 15 before treatment, satisfying the diagnostic criterion of "definite" AIH. Thirty-eight patients (33%) scored between 10 and 15 points and could be classified as "probable" AIH. The serum level of immunoglobulin G (IgG) was elevated in 68 patients (61% of 111 cases tested), and positive titers of antinuclear antibodies (ANA) or smooth muscle antibodies (SMA) were detected in 24 patients (22% of 111 cases tested). Thirty-five of the PSC patients (33% of 105 evaluable biopsy specimens) obtained positive scores for histological features similar to those of AIH, but the total score for histology was in the negative range in 72 patients (69%) because of the presence of biliary changes. The frequent finding of high scores in PSC patients underlines the similarities PSC may have with AIH. A modification of the scoring system, in particular by increasing the negative score for histological biliary changes, would improve its potential to discriminate between AIH and PSC.     

Non-hierarchical control of a flexible manufacturing cell

As hierarchically controlled computer-integrated manufacturing systems growthey tend to become complex and their designability, maintainability, expandability and fault tolerance deteriorate. As an alternative, herterarchical control architectures offer prospects of reduced compexity, reduced software development costs, high modularity, high flexibility, and improved fault tolerance. By locating decision making where information originates, global information is reduced to a minimum, scheduling becomes dynamic, machines and parts become “intelligent” entities that cooperatively interact, and the overall system is decomposed into functionally simplified, modular parts.Three flexible machining cell control systems have been constructed at the University of Wisconsin-Madison and are described in this paper: a centralized controller, a hierarchical controller with dynamic scheduling, and a fully distributed heterarchical controller with “intelligent parts”. Comparative results are reported showing that the heterarchical approach possesses a number of advantages including increased fault-tolerance, inherent adaptability and reconfigurability, decreased complexity, and reduced software development cost.     

Domains of DnaA protein involved in interaction with DnaB protein, and in unwinding the Escherichia coli chromosomal origin

DnaA protein of Escherichia coli is a sequence-specific DNA-binding protein required for the initiation of DNA replication from the chromosomal origin, oriC. It is also required for replication of several plasmids including pSC101, F, P-1, and R6K. A collection of monoclonal antibodies to DnaA protein has been produced and the primary epitopes recognized by them have been determined. These antibodies have also been examined for the ability to inhibit activities of DNA binding, ATP binding, unwinding of oriC, and replication of both an oriC plasmid, and an M13 single-stranded DNA with a proposed hairpin structure containing a DnaA protein-binding site. Replication of the latter DNA is dependent on DnaA protein by a mechanism termed ABC priming. These studies suggest regions of DnaA protein involved in interaction with DnaB protein, and in unwinding of oriC, or low-affinity binding of ATP.     

Redox properties of human medium-chain acyl-CoA dehydrogenase, modulation by charged active-site amino acid residues

The modulation of the electron-transfer properties of human medium-chain acyl-CoA dehydrogenase (hwtMCADH) has been studied using wild-type and site-directed mutants by determining their midpoint potentials at various pH values and estimating the involved pKs. The mutants used were E376D, in which the negative charge is retained; E376Q, in which one negative charge (pKa approximately 6. 0) is removed from the active center; E99G, in which a different negative charge (pKa approximately 7.3) also is affected; and E376H (pKa approximately 9.3) in which a positive charge is present. Em for hwtMCADH at pH 7.6 is -0.114 V. Results for the site-directed mutants indicate that loss of a negative charge in the active site causes a +0.033 V potential shift. This is consistent with the assumption that electrostatic interactions (as in the case of flavodoxins) and specific charges are important in the modulation of the electron-transfer properties of this class of dehydrogenases. Specifically, these charge interactions appear to correlate with the positive Em shift observed upon binding of substrate/product couple to MCADH [Lenn, N. D., Stankovich, M. T., and Liu, H. (1990) Biochemistry 29, 3709-3715], which coincides with a pK increase of Glu376-COOH from approximately 6 to 8-9 [Rudik, I., Ghisla, S., and Thorpe, C. (1998) Biochemistry 37, 8437-8445]. From the pH dependence of the midpoint potentials of hwtMCADH two mechanistically important ionizations are estimated. The pKa value of approximately 6.0 is assigned to the catalytic base, Glu376-COOH, in the oxidized enzyme based on comparison with the pH behavior of the E376H mutant, it thus coincides with the pK value recently estimated [Vock, P., Engst, S., Eder, M., and Ghisla, S. (1998) Biochemistry 37, 1848-1860]. The pKa of approximately 7.1 is assigned to Glu376-COOH in reduced hwtMCADH. Comparable values for these pKas for Glu376-COOH in pig kidney MCADH are pKox = 6.5 and pKred = 7.9. The Em measured for K304E-MCADH (a major mutant resulting in a deficiency syndrome) is essentially identical to that of hwtMCADH, indicating that the disordered enzyme has an intact active site.     

Assessment of Wilson and NRTL equations in vapor‐liquid equilibria prediction

Abstract

This work considers the application of Wilson and NRTL equations in the multicomponent VLE prediction. We emphasize the critical comparison of partially miscible solution treatment by these two equations. Results revealed NRTL equation performed slightly better than the Wilson equation in data credibility so far as the systems examined are concerned. Estimation of optimum NRTL parameters requires further exploration. Optimization methods of pattern search, gradient search and golden section were employed in this study. All of the computations were performed on an IBM 1130 digital computer.     

Dysfunctional cGMP Signaling Leads to Age-Related Retinal Vascular Alterations and Astrocyte Remodeling in Mice

The nitric oxide–guanylyl cyclase-1–cyclic guanylate monophosphate (NO–GC-1–cGMP) pathway is integral to the control of vascular tone and morphology. Mice lacking the alpha catalytic domain of guanylate cyclase (GC1^−/−) develop retinal ganglion cell (RGC) degeneration with age, with only modest fluctuations in intraocular pressure (IOP). Increasing the bioavailability of cGMP in GC1^−/− mice prevents neurodegeneration independently of IOP, suggesting alternative mechanisms of retinal neurodegeneration. In continuation to these studies, we explored the hypothesis that dysfunctional cGMP signaling leads to changes in the neurovascular unit that may contribute to RGC degeneration. We assessed retinal vasculature and astrocyte morphology in young and aged GC1^−/− and wild type mice. GC1^−/− mice exhibit increased peripheral retinal vessel dilation and shorter retinal vessel branching with increasing age compared to Wt mice. Astrocyte cell morphology is aberrant, and glial fibrillary acidic protein (GFAP) density is increased in young and aged GC1^−/− mice, with areas of dense astrocyte matting around blood vessels. Our results suggest that proper cGMP signaling is essential to retinal vessel morphology with increasing age. Vascular changed are preceded by alterations in astrocyte morphology which may together contribute to retinal neurodegeneration and loss of visual acuity observed in GC1^−/− mice.     

Comparative Assay of Antioxidant Packages for Dimer of Estolide Esters

A series of 26 different antioxidants and commercial antioxidant packages designed for petroleum‐based materials, containing both natural and synthetic‐based materials, were evaluated with dimeric coconut‐oleic estolide 2‐ethylhexyl ester (2‐EH), a bio‐based material. The different antioxidants were categorized into different classes of phenolic, aminic, and blended/others materials. The oxidation onset temperatures (OT) using non‐isothermal pressurized differential scanning calorimetry (PDSC) were measured and recorded under previously reported standard conditions. The aminic series gave the best resistance to oxidation as defined by the PDSC method with OT of 246.6 and 244.7 °C for the best two performers, which was a 38 °C improvement over the uninhibited or unformulated dimer estolide material. The phenolic series, containing most of the naturally occurring antioxidants, was the least successful formulation package for the dimer estolide. The blended/other materials, which were specifically designed for petroleum‐based lubricants, did not have the best OT, since the estolides and other bio‐based materials interact differently than their petroleum counterparts. A number of potential antioxidants have been identified as useful additives for the estolides esters. The OT of the estolide and formulated materials correlated well with other bio‐based materials such as biodiesel.     

Threshold lowering in GaN micropillar lasers by means of spatiallyselective optical pumping

A new optical pumping method is demonstrated for creating a population inversion in GaN micropillar cavities with circular symmetry. This approach employs an axicon lens to produce a ring-shaped optical beam and provides for independent control of ring thickness and diameter. By bringing the pump beam into coincidence with whispering gallery modes confined near the outer rim of the cavity, we achieve a significant reduction in the threshold pump intensity for room-temperature operation of GaN micropillar lasers