Brain edema : a valid endpoint for measuring hepatic encephalopathy?

Hepatic encephalopathy (HE) is a major complication of liver failure/disease which frequently develops during the progression of end-stage liver disease. This metabolic neuropsychiatric syndrome involves a spectrum of symptoms, including cognition impairment, attention deficits and motor dysfunction which eventually can progress to coma and death. Pathologically, HE is characterized by swelling of the astrocytes which consequently leads to brain edema, a common feature found in patients with acute liver failure (ALF) as well as in cirrhotic patients suffering from HE. The pathogenic factors involved in the onset of astrocyte swelling and brain edema in HE are unresolved. However, the role of astrocyte swelling/brain edema in the development of HE remains ambiguous and therefore measuring brain edema as an endpoint to evaluate HE is questioned. The following review will determine the effect of astrocyte swelling and brain edema on neurological function, discuss the various possible techniques to measure brain edema and lastly to propose a number of neurobehavioral tests to evaluate HE

Waldschmidt constants for Stanley-Reisner ideals of a class of graphs

In the present note we study Waldschmidt constants of Stanley-Reisner ideals of a hypergraph and a graph with vertices forming a bipyramid over a planar n-gon. The case of the hypergraph has been studied by Bocci and Franci. We reprove their main result. The case of the graph is new. Interestingly, both cases provide series of ideals with Waldschmidt constants descending to 1. It would be interesting to known if there are bounded ascending sequences of Waldschmidt constants.Comment: 7 pages, 2 figure

SLoMo: automated site localization of modifications from ETD/ECD mass spectra

Recently, software has become available to automate localization of phosphorylation sites from CID data and to assign associated confidence scores. We present an algorithm, SLoMo (Site Localization of Modifications), which extends this capability to ETD/ECD mass spectra. Furthermore, SLoMo caters for both high and low resolution data and allows for site-localization of any UniMod post-translational modification. SLoMo accepts input data from a variety of formats (e.g., Sequest, OMSSA). We validate SLoMo with high and low resolution ETD, ECD, and CID data

Kinetic evaluation of human cloned coproporphyrinogen oxidase using a ring isomer of the natural substrate

Background: The enzyme coproporphyrinogen oxidase (copro\u27gen oxidase) converts coproporphyrinogen-Ill (GIII) to protoporphyrinogen-IX via an intermediary monovinyl porphyrinogen. The A ring isomer coproporphyrinogen-IV (C-IV) has previously been shown to be a substrate for copro\u27gen oxidase derived from avian erythrocytes. In contrast to the authentic substrate (GIII) where only a small amount of the monovinyl intermediate is detected, C-IV gives rise to a monovinyl intermediate that accumulates before being converted to an isomer of protoporphyrinogen-IX. No kinetic studies have been carried out using the purified human copro\u27gen oxidase to evaluate its ability to process both the authentic substrate as well as analogs. Material/Methods: Therefore, purified, cloned human copro\u27gen oxidase was incubated with GIII or C-IV at 37 degrees C with various substrate concentrations (from 0.005 mu M to 3.5 mu M). The Km (an indication of molecular recognition) and Kcat (turnover number) values were determined. Results: The Km value for total product formation was about the same with either C-III or C-IV indicating the same molecular recognition. However, the catalytic efficiency (Kcat/Km) of the enzyme for total product formation was not more than two fold higher using GIII relative to C-IV. Conclusions: Since the Km values are about the same for either substrate and the total Kcat/Km values are within two fold of each other, this could correlate with the increase of severity of porphyrias with monovinyl accumulation. The ability of the increased levels of C-IV to compete with the authentic substrate has important implications for clinical porphyrias

Absence of Evidence Is Not Evidence of Absence: The Color-Density Relation at Fixed Stellar Mass Persists to z ~ 1

We use data drawn from the DEEP2 Galaxy Redshift Survey to investigate the relationship between local galaxy density, stellar mass, and rest-frame galaxy color. At z ~ 0.9, we find that the shape of the stellar mass function at the high-mass (log (M*/Msun) > 10.1) end depends on the local environment, with high-density regions favoring more massive systems. Accounting for this stellar mass-environment relation (i.e., working at fixed stellar mass), we find a significant color-density relation for galaxies with 10.6 < log(M*/Msun) < 11.1 and 0.75 < z < 0.95. This result is shown to be robust to variations in the sample selection and to extend to even lower masses (down to log(M*/Msun) ~ 10.4). We conclude by discussing our results in comparison to recent works in the literature, which report no significant correlation between galaxy properties and environment at fixed stellar mass for the same redshift and stellar mass domain. The non-detection of environmental dependence found in other data sets is largely attributable to their smaller samples size and lower sampling density, as well as systematic effects such as inaccurate redshifts and biased analysis techniques. Ultimately, our results based on DEEP2 data illustrate that the evolutionary state of a galaxy at z ~ 1 is not exclusively determined by the stellar mass of the galaxy. Instead, we show that local environment appears to play a distinct role in the transformation of galaxy properties at z > 1.Comment: 10 pages, 5 Figures; Accepted for publication in MNRA

Technical Challenges Associated with In-Air Wingtip Docking of Aircraft in Forward Flight

Autonomous in-air wingtip docking of aircraft offers significant opportunity for system level performance gains for numerous aircraft applications. Several of the technical challenges facing wingtip docking of fixed-wing aircraft are addressed in this paper, including: close proximity aerodynamic coupling; mechanisms and operations for robust docking; and relative state estimation methods. A simulation framework considering the aerodynamics, rigid-body dynamics, and vehicle controls is developed and used to perform docking sensitivity studies for a system of two 5.5% scale NASA Generic Transport Model aircraft. Additionally, proof of- concept testing of a candidate docking mechanism designed to move the primary wingtip vortex inboard suggests the viability of such an approach for achieving robust docking

Investigation of the catalytic and structural roles of conserved histidines of human coproporphyrinogen oxidase using site-directed mutagenesis

Background: The catalytic contribution of four conserved histidines of human coproporphyrinogen oxidase (CPO) has been investigated using site-directed mutagenesis to change histidine (H) into alanine (A). Material/Methods: The wild-type and mutant enzyme forms were analyzed for their ability to utilize coproporphyrinogen-III, mesoporphvrinogen-VI, and harderoporphyrinogen as substrates. Results: Wild-type CPO had specific activities of 4.9 +/- 0.9 nmole product/min/mg for coproporphyrinogen-III, 1.7 +/- 0.7 nmole ptoduct/min/mg for mesoporphyrinogen-VI, and 5.1 +/- 1.8 nmole product/min/mg for harderoporphyrinogen. The four mutant enzymes were catalytically competent With all three substrates, but to varying degrees. The most affected Mutant was the H158A enzyme which exhibited approximately 50-fold lower activity than wild-type recombinant CPO. Conclusions: Thus, His 158 of human CPO may have a role ill the active site, but none of the conserved histidine residues of human coproporphyrinogen oxidase is essential for catalytic activity although changes in histidines have been implicated in the disease state hereditary coproporphyria