The Role of the Pre-Sensor 1 β Hairpin in Minichromosome Maintenance 2-7 Function

The pre-sensor 1 (PS1) hairpin is found in helicases of the AAA+ family (ATPases associated with a variety of cellular activities) of proteins and is implicated in DNA translocation during DNA unwinding. To determine whether the PS1 b hairpin is required in the eukaryotic replicative helicase, Mcm2-7 (also comprised of AAA+ proteins), we mutated the conserved lysine residue in the PS1 hairpin in each of the S. cerevisiae Mcm subunits to alanine. Only the PS1 hairpin of Mcm3 was essential for viability, while mutation of the PS1 hairpin in the remaining Mcm subunits resulted in minimal phenotypes, with the exception of Mcm7. The viable alleles were synthetic lethal with each other. Mcm2-7 containing Mcm3K499A (Mcm2-73K499A) disrupts helicase activity, yet the ATPase activity of Mcm2-73K499A was similar to the wild type Mcm2-7, and its interaction with single-stranded DNA was subtly altered in vitro. These findings indicate that the PS1 hairpins in the Mcm2-7 subunits have important and distinct functions most evident with Mcm3K499A

Water Demand at Recreation Developments

Design criteria for drinking water systems at recreation developments, particularly summer home type, cause frequent confrontations with regulatory agencies. Developers claim extremely low water use rates due to low occupancy rates, but regulatory agencies are concerned about changes over time from essentially weekend use to more permanent residency and also about occasional peak day water demands similar to those of municipal systems. Little empirical data have been available to resolve such questions. This study included the gathering and analysis of both historic water use measurements and additional daily and instantaneous measurements during peak seasons at 11 Utah and one Wyoming recreation development. The water demand parameters studied included average, peak month, peak day, and instantaneous events at mountain cabins, resort condominiums, marinas, and recreation vehicle campgrounds. The results are compared to existing design criteria of the Utah Division of Environmental Health

An Efficient Adaptive Search Algorithm for Scheduling Real-Time Traffic

Proc. Fourth IEEE International Conference on Network Protocols (ICNP), pp. 14-22, Columbus, OH, October 1996.The article of record as published may be found at http://dx.doi.org/10.1109/ICNP.1996.564885For many service disciplines that provide delay guarantees, the scheduler of a channel repeatedly searches for the smallest element in a set of priority values (or deadlines). It is required that each search finishes within a time bound. Furthermore, the search algorithm should be highly efficient. To meet these requirements, we have developed a search algorithm based upon a new data structure, called adaptive heap; it behaves like a heap most of the time, but adaptively changes its strategy when necessary to satisfy the time bound. We show that the algorithm has optimal worst case time complexity and good average performance. To further improve efficiency, the basic algorithm is extended to include the use of group scheduling. We present empirical results on the performance of adaptive heap search with and without group scheduling. We conclude that adaptive heap search performs as intended, and that group scheduling provides a substantial reduction in the scheduler’s work when channel utilization is high

Predictors of septic shock in patients with methicillin-resistant Staphylococcus aureus bacteremia

SummaryObjectivesRisk factors for septic shock associated with methicillin-resistant Staphylococcus aureus (MRSA) bacteremia are not well described. We designed this study to assess the independent predictors of septic shock in patients with MRSA bacteremia.MethodsThis retrospective chart review included 234 patients with MRSA bacteremia admitted to a tertiary care academic medical center. Cases of septic shock and non-septic shock MRSA bacteremia were compared in terms of patient baseline characteristics and co-morbidities, modes of acquisition, and MRSA genotyping. Independent risk factors were determined by multivariable analysis.ResultsOn univariate analysis the presence of chronic kidney disease, respiratory failure, acute renal failure, staphylococcal cassette chromosome (SCCmec) type II, and higher APACHE II scores were significantly correlated with the presence of septic shock. On multivariate analysis, baseline APACHE II score (adjusted odds ratio (AOR) for 1-point increase 1.13, 95% confidence interval (CI) 1.04–1.22, p=0.005), acute renal failure (AOR 2.57, 95% CI 1.02–6.48, p=0.045), and SCCmec type II (AOR 2.60, 95% CI 1.01–6.75, p=0.049) were independently associated with MRSA bacteremic septic shock.ConclusionsThe development of septic shock associated with MRSA bacteremia was independently correlated with baseline severity of illness, presence of acute renal failure, and an MRSA genotyping consistent with nosocomially acquired MRSA infection

The Effects of Pregnenolone 16α-Carbonitrile Dosing on Digoxin Pharmacokinetics and Intestinal Absorption in the Rat

The effect of Pgp induction in rats by pregnenolone 16α-carbonitrile (PCN) (3 days, 35 mg/kg/d, p.o.) on digoxin pharmacokinetics and intestinal transport has been assessed. After intravenous or oral digoxin dosing the arterial and hepatic portal vein (oral) AUC(0-24h) were significantly reduced by PCN pre-treatment. Biliary digoxin clearance increased 2-fold following PCN treatment. PCN significantly increased net digoxin secretion (2.05- and 4.5-fold respectively) in ileum and colon but not in duodenum or jejunum. This increased secretion correlated with increased Pgp protein expression in ileum and colon. Both intestinal and biliary excretion therefore contribute to altered digoxin disposition following PCN

Integrating the Theory of Sampling into Underground Mine Grade Control Strategies

Grade control in underground mines aims to deliver quality tonnes to the process plant via the accurate definition of ore and waste. It comprises a decision-making process including data collection and interpretation; local estimation; development and mining supervision; ore and waste destination tracking; and stockpile management. The foundation of any grade control programme is that of high-quality samples collected in a geological context. The requirement for quality samples has long been recognised, where they should be representative and fit-for-purpose. Once a sampling error is introduced, it propagates through all subsequent processes contributing to data uncertainty, which leads to poor decisions and financial loss. Proper application of the Theory of Sampling reduces errors during sample collection, preparation, and assaying. To achieve quality, sampling techniques must minimise delimitation, extraction, and preparation errors. Underground sampling methods include linear (chip and channel), grab (broken rock), and drill-based samples. Grade control staff should be well-trained and motivated, and operating staff should understand the critical need for grade control. Sampling must always be undertaken with a strong focus on safety and alternatives sought if the risk to humans is high. A quality control/quality assurance programme must be implemented, particularly when samples contribute to a reserve estimate. This paper assesses grade control sampling with emphasis on underground gold operations and presents recommendations for optimal practice through the application of the Theory of Sampling