The electroactive species in the catalysis of cyclohexadiene to benzene by Rh2(TM4) 4 +2 (TM4=2,5-diisocyano-2,5-dimethylhexane)

Upon further investigation of the recently reported electrocatalytic oxidation of 1,4-cyclohexadiene to benzene by Rh₂(TM4) ₄ ⁺² (TM4=2,5-diisocyano-2,5-dimethylhexane), we have obtained data which strongly implicates the 2e^– oxidized d⁷-d⁷ complex as the electroactive species. This contrasts with the original report which suggested that the le^– oxidized d⁷-d⁸ radical acted as the key species via hydrogen atom abstraction from 1,4-cyclohexadiene. A possible mechanism for the catalysis is proposed.     

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.     

Espresso Reward Learning, Hold the Dopamine: Theoretical Comment on Robinson et al. (2005).

Question: Is dopamine needed for reward learning? Answer: No--at least, not in the brain of a caffeinated dopamine-deficient (DD) mutant mouse. That is the conclusion of an important paper in this issue by S. Robinson, S. M. Sandstrom, V. H. Denenberg, and R. D. Palmiter (see record 2005-01705-001). Those authors demonstrate that reward learning can proceed normally in the brains of DD mice, even though they contain no dopamine at the time of learning, if the mice are given caffeine just before learning. Caffeine activates the DD mice by a nondopaminergic mechanism, allowing them to learn where to obtain food reward in a T-maze runway. Their reward-learning-without-dopamine is revealed on a subsequent test day, when dopamine function is restored by L-dopa administration. Robinson et al. conclude that dopamine is not needed for normal learning about rewards, or for hedonic "liking" of rewards during learning, but rather specifically for a motivational "wanting" component of reward, such as incentive salience. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The Bidirectional Mapping Problem

Mappings between models and languages are essential to support model driven approaches to software development. Those mappings need to be supported by tools. There are different kinds of mapping appropriate for different stages in the development process. This paper focuses on bidirectional mappings between models used to capture software requirements and models used to capture software designs. The properties of such mappings are illustrated using a mapping between models used in the development of web-based, business systems. This motivates and helps identify a set of benchmarks against which approaches to the definition and tooling of such mappings can be judged. The paper concludes with pointers to one approach at addressing the bidirectional mapping problem.     

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.     

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.     

Benchmarking and learning garbage collection delays for resource-restricted graphical user interfaces

Tablets, smartphones, and wearables have limited resources. Applications on these devices employ a graphical user interface (GUI) for interaction with users. Language runtimes for GUIs employ dynamic memory management using garbage collection (GC). However, GC policies and algorithms are designed for data centers and cloud computing, but they are not necessarily ideal for resource-constrained embedded devices. In this article, we present GUI GC, a JavaFX GUI benchmark, which we use to compare the performance of the four GC policies of the Eclipse OpenJ9 Java runtime on a resource-constrained environment. Overall, our experiments suggest that the default policy Gencon registered significantly lower execution times than its counterparts. The region-based policy, Balanced, did not fully utilize blocking times; thus, using GUI GC, we conducted experiments with explicit GC invocations that measured significant improvements of up to 13.22% when multiple CPUs were available. Furthermore, we created a second version of GUI GC that expands on the number of controllable load-stressing dimensions; we conducted a large number of randomly configured experiments to quantify the performance effect that each knob has. Finally, we analyzed our dataset to derive suitable knob configurations for desired runtime, GC, and hardware stress levels.     

Metalloendopeptidase ADAM-like Decysin 1 (ADAMDEC1) in Colonic Subepithelial PDGFRα+ Cells Is a New Marker for Inflammatory Bowel Disease

Metalloendopeptidase ADAM-Like Decysin 1 (ADAMDEC1) is an anti-inflammatory peptidase that is almost exclusively expressed in the gastrointestinal (GI) tract. We have recently found abundant and selective expression of Adamdec1 in colonic mucosal PDGFRα⁺ cells. However, the cellular origin for this gene expression is controversial as it is also known to be expressed in intestinal macrophages. We found that Adamdec1 mRNAs were selectively expressed in colonic mucosal subepithelial PDGFRα⁺ cells. ADAMDEC1 protein was mainly released from PDGFRα⁺ cells and accumulated in the mucosal layer lamina propria space near the epithelial basement membrane. PDGFRα⁺ cells significantly overexpressed Adamdec1 mRNAs and protein in DSS-induced colitis mice. Adamdec1 was predominantly expressed in CD45⁻ PDGFRα⁺ cells in DSS-induced colitis mice, with only minimal expression in CD45⁺ CD64⁺ macrophages. Additionally, overexpression of both ADAMDEC1 mRNA and protein was consistently observed in PDGFRα⁺ cells, but not in CD64⁺ macrophages found in human colonic mucosal tissue affected by Crohn’s disease. In summary, PDGFRα⁺ cells selectively express ADAMDEC1, which is localized to the colon mucosa layer. ADAMDEC1 expression significantly increases in DSS-induced colitis affected mice and Crohn’s disease affected human tissue, suggesting that this gene can serve as a diagnostic and/or therapeutic target for intestinal inflammation and Crohn’s disease.