Stochastic models and numerical algorithms for a class of regulatory gene networks.

Regulatory gene networks contain generic modules, like those involving feedback loops, which are essential for the regulation of many biological functions (Guido et al. in Nature 439:856-860, 2006). We consider a class of self-regulated genes which are the building blocks of many regulatory gene networks, and study the steady-state distribution of the associated Gillespie algorithm by providing efficient numerical algorithms. We also study a regulatory gene network of interest in gene therapy, using mean-field models with time delays. Convergence of the related time-nonhomogeneous Markov chain is established for a class of linear catalytic networks with feedback loops.

High-resolution three-dimensional aortic magnetic resonance angiography and quantitative vessel wall characterization of different atherosclerotic stages in a rabbit model

PURPOSE: Atherosclerosis results in a considerable medical and socioeconomic impact on society. We sought to evaluate novel magnetic resonance imaging (MRI) angiography and vessel wall sequences to visualize and quantify different morphologic stages of atherosclerosis in a Watanabe hereditary hyperlipidemic (WHHL) rabbit model. MATERIAL AND METHODS: Aortic 3D steady-state free precession angiography and subrenal aortic 3D black-blood fast spin-echo vessel wall imaging pre- and post-Gadolinium (Gd) was performed in 14 WHHL rabbits (3 normal, 6 high-cholesterol diet, and 5 high-cholesterol diet plus endothelial denudation) on a commercial 1.5 T MR system. Angiographic lumen diameter, vessel wall thickness, signal-/contrast-to-noise analysis, total vessel area, lumen area, and vessel wall area were analyzed semiautomatically. RESULTS: Pre-Gd, both lumen and wall dimensions (total vessel area, lumen area, vessel wall area) of group 2 + 3 were significantly increased when compared with those of group 1 (all P < 0.01). Group 3 animals had significantly thicker vessel walls than groups 1 and 2 (P < 0.01), whereas angiographic lumen diameter was comparable among all groups. Post-Gd, only diseased animals of groups 2 + 3 showed a significant (>100%) signal-to-noise ratio and contrast-to-noise increase. CONCLUSIONS: A combination of novel 3D magnetic resonance angiography and high-resolution 3D vessel wall MRI enabled quantitative characterization of various atherosclerotic stages including positive arterial remodeling and Gd uptake in a WHHL rabbit model using a commercially available 1.5 T MRI system.

Coffee consumption attenuates short-term fructose-induced liver insulin resistance in healthy men.

BACKGROUND: Epidemiologic and experimental data have suggested that chlorogenic acid, which is a polyphenol contained in green coffee beans, prevents diet-induced hepatic steatosis and insulin resistance. OBJECTIVE: We assessed whether the consumption of chlorogenic acid-rich coffee attenuates the effects of short-term fructose overfeeding, dietary conditions known to increase intrahepatocellular lipids (IHCLs), and blood triglyceride concentrations and to decrease hepatic insulin sensitivity in healthy humans. DESIGN: Effects of 3 different coffees were assessed in 10 healthy volunteers in a randomized, controlled, crossover trial. IHCLs, hepatic glucose production (HGP) (by 6,6-d2 glucose dilution), and fasting lipid oxidation were measured after 14 d of consumption of caffeinated coffee high in chlorogenic acid (C-HCA), decaffeinated coffee high in chlorogenic acid, or decaffeinated coffee with regular amounts of chlorogenic acid (D-RCA); during the last 6 d of the study, the weight-maintenance diet of subjects was supplemented with 4 g fructose · kg(-1) · d(-1) (total energy intake ± SD: 143 ± 1% of weight-maintenance requirements). All participants were also studied without coffee supplementation, either with 4 g fructose · kg(-1) · d(-1) (high fructose only) or without high fructose (control). RESULTS: Compared with the control diet, the high-fructose diet significantly increased IHCLs by 102 ± 36% and HGP by 16 ± 3% and decreased fasting lipid oxidation by 100 ± 29% (all P < 0.05). All 3 coffees significantly decreased HGP. Fasting lipid oxidation increased with C-HCA and D-RCA (P < 0.05). None of the 3 coffees significantly altered IHCLs. CONCLUSIONS: Coffee consumption attenuates hepatic insulin resistance but not the increase of IHCLs induced by fructose overfeeding. This effect does not appear to be mediated by differences in the caffeine or chlorogenic acid content. This trial was registered at clinicaltrials.gov as NCT00827450.

Lag-one autocorrelation in short series: Estimation and hypothesis testing

In the first part of the study, nine estimators of the first-order autoregressive parameter are reviewed and a new estimator is proposed. The relationships and discrepancies between the estimators are discussed in order to achieve a clear differentiation. In the second part of the study, the precision in the estimation of autocorrelation is studied. The performance of the ten lag-one autocorrelation estimators is compared in terms of Mean Square Error (combining bias and variance) using data series generated by Monte Carlo simulation. The results show that there is not a single optimal estimator for all conditions, suggesting that the estimator ought to be chosen according to sample size and to the information available of the possible direction of the serial dependence. Additionally, the probability of labelling an actually existing autocorrelation as statistically significant is explored using Monte Carlo sampling. The power estimates obtained are quite similar among the tests associated with the different estimators. These estimates evidence the small probability of detecting autocorrelation in series with less than 20 measurement times.

Thin Bonded Concrete Overlay with Fast Track Concrete, HR-531, Condition and Performance Report, 1987

This report is a supplement to one issued in late summer 1986 which covered construction on U.S. 71, in Buena Vista County Iowa. The work involved rehabilitation of an older 20 feet wide pavement by placing a four inch thick bonded concrete overlay monolithically with two feet of widening on each side. The work was performed on one lane at a time while construction traffic and limited public traffic used the adjacent traffic lane. When work on the first lane was complete traffic was moved onto it and rehabilitation was completed on the second lane. This report covers the condition of the rehabilitated roadway in May 1987 after the first winter. The condition is described by visual observations, core conditions, and various test results including core compressive strength, direct shear tests on cores for bond strength, profilometer results and delamtect test results.

Metric Short Course for the Office of Bridges and Structures, HR-378, 1995

This metric short course was developed in response to a request from the Office of Bridges and Structures to assist in the training of engineers in the use of metric units of measure which will be required in all highway designs and construction after September 30, 1996 (CFR Presidential Executive Order No. 12770). The course notes which are contained in this report, were developed for a half-day course. The course contains a brief review of metrication in the U.S., metric units, prefixes, symbols, basic conversions, etc. The unique part of the course is that it presents several typical bridge calculations (such as capacity of reinforced concrete compression members, strength of pile caps, etc.) worked two ways: inch-pound units throughout with end conversion to metric and initial hard conversion to metric with metric units throughout. Comparisons of partial results and final results (obtained by working the problems the two ways) are made for each of the example problems.

Fast Track Portland Cement Concrete Pavement, HR-538, 1997

In 1987, 1.5 km (0.935 mi.) of Spruce Hill Drive in Bettendorf, Iowa was reconstructed. It is an arteriel street with commercial usage on both termini with single family residential dwellings along most of the project. A portland cement concrete (PCC) pavement design was selected, but a 14 day curing period would have been an undue hardship on the residents and commercial businesses. An Iowa DOT Class F fast track concrete was used so the roadway could be used in 7 to 10 days. The Class F concrete with fly ash was relatively sticky and exhibited early stiffening problems and substantial difficulty in obtaining the target entrained air content of 6.5%. These problems were never completely resolved on the project. Annual visual field reviews were conducted through 1996. In November 1991, severe premature distress was identified on the westbound two lanes of the full width replacement. The most deteriorated section in a sag vertical, 152 m (500 ft.) of the westbound roadway, was replaced in 1996. Premature distress has been identified on a dozen other conventional PCC Iowa pavements constructed between 1983 and 1989, so the deterioration may not be related to the fact that it was fast track pavement.

Rapid, simple and high yield production of recombinant proteins in mammalian cells using a versatile episomal system.

Many research projects in life sciences require purified biologically active recombinant protein. In addition, different formats of a given protein may be needed at different steps of experimental studies. Thus, the number of protein variants to be expressed and purified in short periods of time can expand very quickly. We have therefore developed a rapid and flexible expression system based on described episomal vector replication to generate semi-stable cell pools that secrete recombinant proteins. We cultured these pools in serum-containing medium to avoid time-consuming adaptation of cells to serum-free conditions, maintain cell viability and reuse the cultures for multiple rounds of protein production. As such, an efficient single step affinity process to purify recombinant proteins from serum-containing medium was optimized. Furthermore, a series of multi-cistronic vectors were designed to enable simultaneous expression of proteins and their biotinylation in vivo as well as fast selection of protein-expressing cell pools. Combining these improved procedures and innovative steps, exemplified with seven cytokines and cytokine receptors, we were able to produce biologically active recombinant endotoxin free protein at the milligram scale in 4-6weeks from molecular cloning to protein purification.

Islands of euchromatin-like sequence and expressed polymorphic sequences within the short arm of human chromosome 21.

The goals of the human genome project did not include sequencing of the heterochromatic regions. We describe here an initial sequence of 1.1 Mb of the short arm of human chromosome 21 (HSA21p), estimated to be 10% of 21p. This region contains extensive euchromatic-like sequence and includes on average one transcript every 100 kb. These transcripts show multiple inter- and intrachromosomal copies, and extensive copy number and sequence variability. The sequencing of the "heterochromatic" regions of the human genome is likely to reveal many additional functional elements and provide important evolutionary information.

Special Cements for Fast Track Concrete, MLR-87-4, 1988

Two specialty cements are currently being marketed as a way to achieve portland cement concrete pavement opening strengths at less than 12 hours after placement. The cements are Pyrament from Pyrament/Lone Star Industries of Houston, Texas and Ideal Regulated-Set (RS) Portland Cement from Ideal Cement Company of Saratoga, Arkansas. The objective of the study was to evaluate the strength gain and durability of concrete produced with Pyrament and Ideal RS cement as Fast Track concrete. Mixes with 610 lb/cu yd (362 kg/cu m) cement were made and tested. Both Pyrament and Ideal RS are capable of producing pavement opening times less than 12 hours. Recent changes to Ideal RS cement have produced concrete flexural strengths of 550 psi (3792 kPa) at 4 hours in Iowa tests. Freeze/thaw durability of the concrete was not adversely affected by using either cement.

Evaluation of Type I Cement Fast Track Concrete, MLR-87-6, 1988

There are projects where opening the pavement to traffic in less than the 5 to 7 days is needed, but an 8 to 12 hour opening time is not necessary. The study examined fast track concrete with Type I cement and admixtures. The variables studied were: (1) cure temperature, (2) cement brand, (3) accelerators, and (4) water reducers. A standard water reducer and curing blankets appear to be effective at producing a 24 hour to 36 hour opening strength. An accelerator and/or high range water reducer may produce opening strength in 12 to 24 hours. Calcium chloride was most effective at achieving high-early strength.

Comparison of short-wood forwarding systems used in Iberia

Abstract

How do the different components of episodic memory develop? Role of executive functions and short-term feature-binding abilities.

This study investigated the development of all 3 components of episodic memory (EM), as defined by Tulving, namely, core factual content, spatial context, and temporal context. To this end, a novel, ecologically valid test was administered to 109 participants aged 4-16 years. Results showed that each EM component develops at a different rate. Ability to memorize factual content emerges early, whereas context retrieval abilities continue to improve until adolescence, due to persistent encoding difficulties (isolated by comparing results on free recall and recognition tasks). Exploration of links with other cognitive functions revealed that short-term feature-binding abilities contribute to all EM components, and executive functions to temporal and spatial context, although ability to memorize temporal context is predicted mainly by age.

Quantitative X-Ray Diffraction Measurements by Fast Scanning, HR-111

Two goals were pursued in this research: first, to evaluate statistically some effects of sample preparation and instrument geometry on reproducibility of X-ray diffraction intensity data; and second, to develop a procedure for finding minimum peak and background counting times for a desired level of accuracy. The ratio of calcite to dolomite in limestones was determined in trials. Ultra-fine wet grinding of the limestone in porcelain impact type ball mill gave most consistent X-ray results, but caused considerable line broadening, and peaks were best measured on an area count basis. Sample spinning reduced variance about one third, and a coarse beam-medium detector slit arrangement was found to be best. An equation is developed relating coefficient of variation of a count ratio to peak and background counts. By use of the equation or graphs the minimum coefficient of variation is predicted from one fast scan, and the number and optimum arrangement of additional counting periods to reduce variation to a desired limit may be obtained. The calculated coefficient is the maximum which may be attributed to the counting statistic but does not include experimental deviations.

Thin Bonded Concrete Overlay with Fast Track Concrete, Final Report, HR-531, 1990

Pavements have been overlaid with thin bonded portland cement concrete (PCC) for several years. These projects have had traffic detoured for a period of 5-10 days. These detours are unacceptable to the traveling public and result in severe criticism. The use of thin bonded fast track overlay was promoted to allow a thin bonded PCC overlay with minimal disruption of local traffic. This project demonstrated the concept of using one lane of the roadway to maintain traffic while the overlay was placed on the other and then with the rapid strength gain of the fast track concrete, the construction and local traffic is maintained on the newly placed, thin bonded overlay. The goals of this project were: 1. Traffic usage immediately after placement and finishing. 2. Reduce traffic disruption on a single lane to less than 5 hours. 3. Reduce traffic disruption on a given section of two-lane roadway to less than 2 days. 4. The procedure must be economically viable and competitive with existing alternatives. 5. Design life for new construction equivalent to or in excess of conventional pavements. 6. A 20 year minimum design life for rehabilitated pavements.