Data management and analysis for high-throughput DNA sequencingprojects

The rapid advances in molecular biology have begun to shift many of the bottlenecks in genome research from the laboratory to the data analysis facility. The pace at which this has occurred creates a situation in which software development always has to catch up with the flow of data. Since such large-scale processes were not anticipated, the analysis infrastructure has not been fully established. Furthermore, most systems that have been built were designed by the biologists who collected the data. More recently, computer scientists, mathematicians, and engineers have taken an interest in this problem. This has had a positive effect, since it has created a tight synergy between the informatics and the biology. Several principles affected the design of the system developed at TIGR. Each of the sample preparation, sequencing, and analysis steps had to be managed, scheduled, and tracked. This information had to be made readily available to those who needed it for carrying out their tasks. Different skill levels of the users had to be taken into account. The degree of human intervention at each step had to be evaluated and built into the design. A mixed processing environment of Macintosh and Unix platforms had to be integrated. Most importantly, the system had to save time, reduce error, and ensure uniformity of the analysis and quality of the results. In the authors' experience, the tools they have built work well because of their early decisions as to which systems to use for development. The authors settled on a robust relational database management system (Sybase) and a portable development environment (C, C++)     

Variation in phosphoric acid concentration and treatment time and HEMA diffusion through dentin

IGF-1 and its receptors have been identified in many tissues including the central nervous system (CNS). We have previously demonstrated that injection of insulin directly into the cerebral ventricles (ICV) is followed by a drop in mean arterial pressure (MAP) associated with an increase in skeletal muscle blood flow. Given the similarities between the IGF-1 and insulin molecules and their respective receptors, we have investigated the effect of ICV administration of IGF-1 on systemic blood pressure and blood flow in selected vascular beds. ICV cannulas were implanted into normal rats and the animals were allowed to recover for 3 to 4 days. The femoral artery and vein were cannulated for blood pressure monitoring and blood sampling and blood flow probes placed around the iliac, the renal and the superior mesenteric artery were used to assess regional blood flow. ICV injection of IGF-1 resulted in a significant decrease in MAP with a nadir at 15 minutes and a gradual return to baseline by 60 minutes; heart rate increased 40 minutes after the injection. IGF-1 significantly enhanced vascular flow and conductance in the iliac, but not in the renal and superior mesenteric arteries. The effects of IGF-1 were much smaller than those observed previously with equimolar amounts of insulin. We conclude that IGF-1 can decrease MAP by selectively increasing blood flow to skeletal muscle through a direct action on the central nervous system.     

Inhibition of nitric oxide synthesis extends cerebrovascular autoregulation during hypertension

In anesthetized intact rats, cerebral blood flow is autoregulated until mean arterial blood pressure (MAP) exceeds 150 mmHg. At higher pressures cerebral blood flow breaks through autoregulation and rapidly increases. However, interruption of the arterial baroreceptor reflex eliminates breakthrough of autoregulation. Thus, breakthrough may reflect active rather than passive vasodilatation. We, therefore, sought to determine if breakthrough depends upon synthesis of the vasodilator nitric oxide. Thirty-eight anesthetized adult male Sprague-Dawley rats were studied. In all, MAP was raised by slow i.v. infusion of phenylephrine. In rats pretreated with the nitric oxide synthase inhibitor L-nitroarginine (L-NA; 22 mg/kg i.v.) or with a combination of L-NA plus D-arginine (D-Arg; 240 mg/kg i.v.), breakthrough did not occur even when MAP exceeded 185 mmHg (L-NA) and 165 mmHg (D-Arg). In contrast, breakthrough occurred in rats treated with L-NA plus L-arginine (L-Arg; 240 mg/kg i.v.) and in rats whose basal vascular tone had been increased by pretreatment with arginine vasopressin prior to infusion of phenylephrine. Removal of sympathetic innervation to cerebral vessels attenuated, but did not eliminate, effects of L-NA on breakthrough. Thus, vasodilatation seen with breakthrough of autoregulation depends upon release of nitric oxide or a nitric oxide donor.     

Flow reversal in the descending aorta: a guide to intraoperative assessment of aortic regurgitation with transesophageal echocardiography

This study assessed the value of biplane transesophageal echocardiographic assessment of diastolic flow reversal in the descending aorta as an alternative to Doppler color flow imaging in determining severity of aortic regurgitation. In 45 patients undergoing cardiac operations, the severity of aortic regurgitation was assessed by semiquantitative grading of the width of the Doppler color flow regurgitant jet relative to the left ventricular outflow tract, and the presence of diastolic flow reversal was assessed with pulsed-wave Doppler measurements at three sites in the descending aorta. In four patients, the diastolic flow reversal method was the only available form of assessment because of inadequate visualization of the left ventricular outflow tract beneath a mitral valve prosthesis. Diastolic flow reversal in the descending aorta was not observed in patients without aortic regurgitation and was always present in patients with severe aortic regurgitation. Aortic valve replacement successfully eliminated descending aortic flow reversal in all 19 patients in whom it was present before valve replacement. Identification of diastolic flow reversal at multiple sites in the descending aorta with biplane transesophageal echocardiography helps to confirm the presence of severe aortic regurgitation and can serve as an alternative method of assessment when visualization of the left ventricular outflow tract is impaired.     

The Bi2O3-SrO phase diagram

The phase relations in the Bi₂O₃-SrO system have been examined in air at temperatures above 740 °C. Intermediate phases were found to agree with previous work, but the homogeneity ranges and high-temperature phase relationships were in some cases at variance. A modified phase diagram is proposed.     

The effect of random vaccine response on the vaccination coverage required to prevent epidemics

The response people have to vaccination varies because their immune systems differ and vaccine failures occur. Here we consider the effect that a random response, independent for each vaccinee, has on the vaccination coverage required to prevent epidemics in a large community. For a community of uniformly mixing individuals an explicit expression is found for the critical vaccination coverage (CVC) and the effect of the vaccine response is determined entirely by the mean E(AB), where A and B, respectively, reflect the infectivity and susceptibility of a vaccinated individual. This result shows that the usual concept of vaccine efficacy, which focuses on the amount of protection the vaccine provides the vaccinee against infection, is not adequate to describe the requirements for preventing epidemics when vaccination affect infectivity. The estimation of E(AB) poses a problem because A and B refer to the vaccine response of the same individual. Similar results are found when there are different types of individual, but now the mean E(AB) may differ between types. However, for a community made up of households it is shown that the CVC also depends on other characteristics of the vaccine response distribution. In practice this means that estimating a single measure of vaccine effectiveness is generally not enough to determine the CVC. For a specific community of households it is found that the vaccination coverage required to prevent epidemics decreases as the variation in the vaccine response increases.