Reduction of carbamylated albumin by extended hemodialysis

Introduction Among conventional hemodialysis (CHD) patients, carbamylated serum albumin (C‐Alb) correlates with urea and amino acid deficiencies and is associated with mortality. We postulated that reduction of C‐Alb by intensive HD may correlate with improvements in protein metabolism and cardiac function. Methods One‐year observational study of in‐center nocturnal extended hemodialysis (EHD) patients and CHD control subjects. Thirty‐three patients receiving 4‐hour CHD who converted to 8‐hour EHD were enrolled, along with 20 controls on CHD. Serum C‐Alb, biochemistries, and cardiac MRI parameters were measured before and after 12 months of EHD. Findings EHD was associated with reduction of C‐Alb (average EHD change ?3.20 mmol/mol [95% CI ?4.23, ?2.17] compared to +0.21 [95% CI ?1.11, 1.54] change in CHD controls, P < 0.001). EHD was also associated with increases in average essential amino acids (in standardized units) compared to CHD (+0.38 [0.08, 0.68 95%CI]) vs. ?0.12 [?0.50, 0.27, 95% CI], P = 0.047). Subjects who reduced C‐Alb more than 25% were found to have reduced left ventricular mass, increased urea reduction ratio, and increased serum albumin compared to nonresponders, and % change in C‐Alb significantly correlated with % change in left ventricular mass. Discussion EHD was associated with reduction of C‐Alb as compared to CHD, and reduction of C‐Alb by EHD correlates with reduction of urea. Additional studies are needed to test whether reduction of C‐Alb by EHD also correlates with improved clinical outcomes.     

Approximation Algorithms for the Directed k-Tour and k-Stroll Problems

We consider two natural generalizations of the Asymmetric Traveling Salesman problem: the k-Stroll and the k-Tour problems. The input to the k-Stroll problem is a directed n-vertex graph with nonnegative edge lengths, an integer k, as well as two special vertices s and t. The goal is to find a minimum-length s-t walk, containing at least k distinct vertices (including the endpoints s,t). The k-Tour problem can be viewed as a special case of k-Stroll, where s=t. That is, the walk is required to be a tour, containing some pre-specified vertex s. When k=n, the k-Stroll problem becomes equivalent to Asymmetric Traveling Salesman Path, and k-Tour to Asymmetric Traveling Salesman. Our main result is a polylogarithmic approximation algorithm for the k-Stroll problem. Prior to our work, only bicriteria (O(log² k),3)-approximation algorithms have been known, producing walks whose length is bounded by 3OPT, while the number of vertices visited is Ω(k/log² k). We also show a simple O(log² n/loglogn)-approximation algorithm for the k-Tour problem. The best previously known approximation algorithms achieved min(O(log³ k),O(log² n?logk/loglogn)) approximation in polynomial time, and O(log² k) approximation in quasipolynomial time.     

Assessing the performance of a waste characterization expert system

Scientists at the Mississippi State University Diagnostic Instrumentation and Analysis Laboratory and the Idaho National Engineering and Environmental Laboratory (INEEL) have developed an expert system for a noninvasive characterization of containerized radiological waste. The characterization of the containers is necessary for determining their proper disposition. Three prototypes were developed, with each using a different method of handling uncertainty - a fuzzy system, a Bayesian network system, and a neural network system. The performance of each expert system was assessed to determine how well it modeled the decisions made by the INEEL domain expert. The prototype systems were also analyzed to measure the agreement in their decisions, the domain expert's decisions, and the decisions made by two additional experts. The neural network prototype was further analyzed to determine how consistent it was in its assessments. This paper describes the analysis of the performance of the three expert system prototypes.     

How Does Corporate Reputation Affect Customer Loyalty in a Corporate Crisis?

It is widely accepted that corporate reputation plays an important role in determining the impact of crises on firms. Crises may erode corporate reputation. However, reputation may also attenuate the negative effects of crises. This study investigates how corporate reputation moderates the relationship between crisis occurrence and customer loyalty which is expected to decrease given a crisis. Drawing on opposing theories, namely dissonance theory and expectancy‐violation, we conduct a scenario experiment set in the airline industry. Results demonstrate that the moderating effect is weaker in the case of a favourable corporate reputation. This may indicate that a pre‐existing favourable reputation does not shield the firm from the negative effects of the crisis, but may rather present a liability because customers have higher expectations with regard to well‐reputed firms. Contrary to that, ill‐reputed firms have less to lose in the case of a crisis and suffer comparatively smaller decreases in customer loyalty. Marketing management might take into account the role of crisis and reputation management for customer bonding strategies while crisis management should recognize the importance of reputation effects in crises given their impact on customer loyalty and firm profitability.     

Sample preparation strategies for targeted proteomics via proteotypic peptides in human blood using liquid chromatography tandem mass spectrometry

The simultaneous quantification of protein concentrations via proteotypic peptides in human blood by liquid chromatography coupled to quadrupole MS/MS is an important field of bioanalytical research with a high potential for routine diagnostic applications. This review summarizes currently available sample preparation procedures and trends for absolute protein quantification in blood using LC-MS/MS. It discusses approaches of transferring established qualitative protocols to a quantitative analysis regarding their reliability and reproducibility. Techniques used to enhance method sensitivity such as the depletion of high-abundant proteins or the immunoaffinity enrichment of proteins and peptides are described. Furthermore, workflows for (i) protein denaturation, (ii) disulfide bridge reduction and (iii) thiol alkylation as well as (iv) enzymatic digestion for absolute protein quantification are presented. The main focus is on the tryptic digestion as a bottleneck of protein quantification via proteotypic peptides. Conclusively, requirements for a high-throughput application are discussed.     

Immuno-SEM characterization of developing bovine cartilage

Collagen is a vital material in the tissues of living organisms. Found almost everywhere in the human body, collagen is important in connective tissues, bone growth, and cartilage. Collagen XI makes up a very small portion of the cartilaginous tissue; however, it plays a key role in cartilaginous tissue. Collagen XI and two collagen XI isoforms, V1b and V2, are critical in the ossification process. The location of collagen XI, V1b, V2, and their specific functions in the ossification process within developing bovine cartilage are not well characterized. In this work, the location of collagens I, II, XI and two collagen XI isoforms, V1b and V2, present in developing bovine cartilage are investigated using the immuno-SEM technique. The results for the locations of collagen I and II indicate a high level of consistency with previous work, thus showing that the technique of immuno-SEM can be used with confidence to determine the location of various collagen types within cartilaginous and mineralized tissue. This work has shown that collagen XI is present in the lower hypertrophic region and also in a pericellular arrangement, within about two microns of cell walls, throughout the cartilaginous tissue. V1b is expressed in the articular surface, mineralized region, resting zone, and the distal edge of the diaphysis. The V2 isoform is most strongly expressed in areas of newly forming cartilage, and disappears with chondrocyte maturation. V2 is present in the distal edge of the epiphysis, as well as in mineralized tissue. Collagen XI and two of its isoforms, V1b and V2, are thought to play a critical role in the ossification process. However, this role is not well understood, and is still being characterized. The detection of collagen XI and two of its isoforms in the osteo-chondral junction as well as at a joint surface further point to collagen XI, V1b, and V2 playing a vital role in the ossification process, and warrants further research as to their specific function within the ossification process.     

Volume and Enthalpy Changes upon Photoexcitation of Bovine Rhodopsin Derived from Optoacoustic Studies by Using an Equilibrium between Bathorhodopsin and Blue-Shifted Intermediate

A complex multistep model including an equilibrium was used for the first time to analyze data obtained by laser-induced optoacoustic spectroscopy (LIOAS) with bovine rhodopsin in washed membranes (T = 5–32°C). The thermal equilibrium was between bathorhodopsin, batho, and the blue-shifted intermediate (BSI), i.e., batho ⇄ BSI. This analysis considers a 14-ns intermediate detected by LIOAS at 25°C (with similar decay activation parameters as those reported for BSI in solubilized rhodopsin). The energy content of lumirhodopsin (lumi) and the structural volume difference between lumi and rhodopsin were essentially the same (E_lumi. = 80 kJ/mol and ΔV_lumi–rho = 40 mL/mol) for both a model based on a simple batho → BSI → lumi sequence and one including the batho ⇄; BSI equilibrium. However, the structural volume changes for the individual steps batho → BSI and BSI → lumi were markedly changed by the introduction of the equilibrium. With the rate constant for the forward reaction batho → BSI for solubilized rhodopsin determined by Hug et al. (Hug, S.J.; Lewis, W.J.; Einterz, C.M.; Thorgeirsson, T.E.; Kliger, D.S. Biochemistry, 1990 , 29, 1475–1485) the structural volume changes obtained with the equilibrium model are ΔV_BSI-batho = 79 mL/mol and ΔV_lumi-BSI = −44 mL/mol. The resulting batho → BSI expansion is larger than with the sequential model, and ΔV_lumi-BSI is now a contraction instead of an expansion. A small expansion of 5 mL/mol is derived for the formation of batho with both models. The estimated energy content of BSI is clearly higher than the value of lumi. The structural volume changes between batho, BSI, and lumi derived from the equilibrium model correlate better than those from the simple sequential model with the chromophore transition dipole moment changes determined in the literature using linear dichroism measurements. The structural volume changes are discussed in terms of the variations upon transformation of the chromophore–protein interactions.     

Medical Students Time-Sharing an Analog Computer to Learn Physiology

Medical schools, both newly developing and well-established, are recognizing a need for visual and mechanical instructional aids for teaching medicine to future physicians and paramedical personnel. The analog computer has proved to be very useful for these purposes in our hands, since it can be used to simulate many human and animal functions.