Wrapping and interoperating bioinformatics resources using CORBA

Bioinformaticians seeking to provide services to working biologists are faced with the twin problems of distribution and diversity of resources. Bioinformatics databases are distributed around the world and exist in many kinds of storage forms, platforms and access paradigms. To provide adequate services to biologists, these distributed and diverse resources have to interoperate seamlessly within single applications. The Common Object Request Broker Architecture (CORBA) offers one technical solution to these problems. The key component of CORBA is its use of object orientation as an intermediate form to translate between different representations. This paper concentrates on an explanation of object orientation and how it can be used to overcome the problems of distribution and diversity by describing the interfaces between objects.     

Developing and evaluating abstractions for distributed supercomputing

To fully realize its potential, distributed supercomputing requires abstractions and environments facilitating development of efficient applications. In this paper we present PARDIS, a system which addresses this demand by providing support for interoperability of PARallel DIStributed applications. The design of PARDIS is based on the Common Object Request Broker Architecture (CORBA). Like CORBA, it provides interoperability between heterogeneous components by specifying their interfaces in a meta-language, the CORBA IDL, which can be translated into the language of interacting components. However, PARDIS extends the CORBA object model by introducing SPMD objects representing data-parallel computations. This extension allows us to build interactions involving data-parallel components, which exchange distributed data structures whose definitions are captured by distributed sequences. We present microbenchmark results which evaluate the performance potential of SPMD objects for data structures of diverse complexity and different network configurations. Based on these results, we conclude that while encapsulating the existence of multiple interactions SPMD objects also allow their efficient utilization, and therefore constitute a useful abstraction. This revised version was published online in July 2006 with corrections to the Cover Date.     

SPiD: a subtilis protein interaction database.

MOTIVATION: Protein-protein interactions are a potential source of valuable clues in determining the functional role of as yet uncharacterized gene products in metabolic pathways. Graph-like structures emerging from the accumulation of interaction data make it difficult to maintain a consistent and global overview by hand. Bioinformatics tools are needed to perform this graph visualization while maintaining a link to the experimental data. RESULTS: "SPiD" is an online database for exploring networks of interacting proteins in Bacillus subtilis characterized by the two-hybrid system. Graphical displays of interaction networks are created dynamically as users interactively navigate through these networks. Third party applications can interface the database through a Common Object Request Broker Architecture (CORBA) tier. AVAILABILITY: SPiD is available through its web site at http://www-mig.versailles.inra.fr/bdsi/SPiD, and through an Interoperable Object Reference (IOR) and its associated Interface Definition Language (IDL). CONTACT: hoebeke@versailles.inra.fr     

Wrapping SRS with CORBA: from textual data to distributed objects.

MOTIVATION: Biological data come in very different shapes. Databanks are maintained and used by distinct organizations. Text is the de facto Standard exchange format. The SRS system can integrate heterogeneous textual databanks but it was lacking a way to structure the extracted data. RESULTS: This paper presents a CORBA interface to the SRS system which manages databanks in a flat file format. SRS Object Servers are CORBA wrappers for SRS. They allow client applications (visualisation tools, data mining tools, etc.) to access and query SRS servers remotely through an Object Request Broker (ORB). They provide loader objects that contain the information extracted from the databanks by SRS. Loader objects are not hard-coded but generated in a flexible way by using loader specifications which allow SRS administrators to package data coming from distinct databanks. AVAILABILITY: The prototype may be available for beta-testing. Please contact the SRS group (http://srs.ebi.ac.uk).     

Supporting high‐performance I/O in QoS‐enabled ORB middleware

To be an effective platform for high‐performance distributed applications, off-the-shelf Object Request Broker (ORB) middleware, such as CORBA, must preserve communication-layer quality of service (QoS) properties both vertically (i.e., network interface ↔ application layer) and horizontally (i.e., end-to-end). However, conventional network interfaces, I/O subsystems, and middleware interoperability protocols are not well-suited for applications that possess stringent throughput, latency, and jitter requirements. It is essential, therefore, to develop vertically and horizontally integrated ORB endsystems that can be (1) configured flexibly to support high-performance network interfaces and I/O subsystems and (2) used transparently by performance-sensitive applications. This paper provides three contributions to research on high-performance I/O support for QoS-enabled ORB middleware. First, we outline the key research challenges faced by high-performance ORB endsystem developers. Second, we describe how our real-time I/O (RIO) subsystem and pluggable protocol framework enables ORB endsystems to preserve high-performance network interface QoS up to applications running on off-the-shelf hardware and software. Third, we illustrate empirically how highly optimized ORB middleware can be integrated with real-time I/O subsystem to reduce latency bounds on communication between high-priority clients without unduly penalizing low-priority and best-effort clients. Our results demonstrate how it is possible to develop ORB endsystems that are both highly flexible and highly efficient. This revised version was published online in July 2006 with corrections to the Cover Date.     

l-Ribose Production from l-Arabinose by Using Purified l-Arabinose Isomerase and Mannose-6-Phosphate Isomerase from Geobacillus thermodenitrificans

Two enzymes, l-arabinose isomerase and mannose-6-phosphate isomerase, from Geobacillus thermodenitrificans produced 118 g/liter l-ribose from 500 g/liter l-arabinose at pH 7.0, 70°C, and 1 mM Co²⁺ for 3 h, with a conversion yield of 23.6% and a volumetric productivity of 39.3 g liter⁻¹ h⁻¹.l-Ribose, a potential starting material for the synthesis of many l-nucleoside-based pharmaceutical compounds, is not abundant in nature (4, 15, 20). l-Ribose has been synthesized primarily from l-arabinose, l-xylose, d-glucose, d-galactose, d-ribose, and d-mannono-1,4-lactone (1, 13, 20). Recombinant cells containing a NAD-dependent mannitol-1-dehydrogenase produced 52 g/liter l-ribose from 100 g/liter ribitol after fermentation for 72 h (14). However, the volumetric productivity of l-ribose was 26-fold lower than that of the chemical synthetic method starting from l-arabinose (6). l-Ribose isomerase from an Acinetobacter sp., which is most active with l-ribose, showed poor efficiency in the conversion of l-ribulose to l-ribose (9). Recently, l-ribulose was produced with a conversion yield of 19% from the inexpensive sugar l-arabinose using l-arabinose isomerase (AI) from Geobacillus thermodenitrificans (18). l-Ribose has been produced from l-ribulose using mannose-6-phosphate isomerase (MPI) from Bacillus subtilis with a conversion yield of 70% (17). In this study, the production of l-ribose from l-arabinose was demonstrated via a two-enzyme system from G. thermodenitrificans, in which l-ribulose was first produced from l-arabinose by AI and subsequently converted to l-ribose by MPI.The analysis of monosaccharides and the purification and thermostability of AI and MPI from G. thermodenitrificans (2) isolated from compost were performed as described previously (7, 18, 19). The cross-linked enzymes were obtained from the treatment of 0.5% glutaraldehyde (10, 16). The reaction was performed by replacing the reaction solution with 100 g/liter l-arabinose and 1 mM Co²⁺ every 6 h at 70°C and pH 7.0. The reaction volume of 10 ml contained 5 g of the cross-linked enzymes with 8 U/ml AI and 20 U/ml MPI. One unit of AI or MPI activity, which corresponded to 0.0625 or 2.5 mg protein, respectively, was defined as the amount of enzyme required to produce 1 μmol of l-ribulose or l-ribose, respectively, per min at 70°C, pH 7.0, and 1 mM Co²⁺. Unless otherwise stated, the reaction was carried out in 50 mM piperazine-N,N′-bis(2-ethanesulfonic acid) (PIPES) buffer (pH 7.0) in the presence of 1 mM Co²⁺ at 70°C for 4 h. All experiments were performed in triplicate.The recombinant Escherichia coli ER2566 (New England Biolabs, Ipswich, MA) containing pTrc99A plasmid (Pharmacia Biotech, Piscataway, NJ) and the AI or MPI gene was cultivated in a 7-liter fermentor containing 3 liters of chemically defined medium (11). When the cell mass reached 2 g/liter, 10 g/liter lactose was added for enzyme induction. After 14 h, 40 g/liter cells with 13,400 U/liter of AI or 34 g/liter cells with 630 U/liter of MPI was obtained. The enzyme was purified by heat treatment and Hi-Trap anion-exchange chromatography. The purification yields of AI and MPI were 21 and 78%, respectively, and the levels of purity for the concentrated AI and MPI by gene scanning were 48 and 92%, respectively. Maximum l-ribose production from l-arabinose by AI and by MPI in 10 ml of total volume was observed at pH 7.0, 70°C, and 1 mM Co²⁺ (data not shown). Half-lives for the two-enzyme system containing 10 mM l-arabinose, 0.2 U/ml AI, and 0.5 U/ml MPI at 60, 65, 70, 75, and 80°C were 1,216, 235, 48, 26, and 12 h, respectively. The use of Co²⁺ may be disadvantageous, as it is fairly toxic. This problem can be solved by using Mn²⁺ instead of Co²⁺. When Mn²⁺ was used in the reaction with the same amounts of enzymes, the conversion yield was the same as that obtained with Co²⁺, even though the volumetric productivity was lower than that with Co²⁺ (data not shown).The effect of the ratio of AI to MPI in the two-step enzymatic production of l-ribose from l-arabinose was investigated by mixing the enzyme solutions (8 U/ml AI and 20 U/ml MPI) to obtain AI/MPI ratios ranging from 10:90 to 90:10 (vol/vol) (Fig. ​(Fig.1).1). The reactions were run with 300 g/liter l-arabinose. Maximum l-ribose production was observed at a volume ratio of 50:50 of the enzyme solutions. The effects of enzyme concentration on l-ribose production were investigated at the optimal unit ratio (AI/MPI ratio, 1:2.5) with 500 g/liter l-arabinose and AI and MPI concentrations from 0.4 and 1.0 U/ml, respectively, to 9.2 and 23.0 U/ml, respectively (Fig. ​(Fig.2A).2A). l-Ribose production increased with increasing amounts of enzymes until reaching a plateau at 8 U/ml AI and 20 U/ml MPI. The effect of substrate concentration on l-ribose production was evaluated at l-arabinose concentrations ranging from 15 to 500 g/liter with 8 U/ml AI and 20 U/ml MPI (Fig. ​(Fig.2B).2B). The production of both l-ribose and l-ribulose, an intermediate, increased with increasing substrate level. The results suggest that concentrations of substrate above 500 g/liter l-arabinose might cause the increased production. The conversion yields of l-ribose and l-ribulose from l-arabinose were constant at 32% and 14%, respectively, within an initial concentration of 100 g/liter l-arabinose, indicating that the reactions reached equilibrium at an l-arabinose/l-ribulose/l-ribose ratio of 54:14:32, which was in agreement with the calculated equilibrium (17). However, at l-arabinose concentrations above 100 g/liter, the conversion yields of l-ribose and l-ribulose from l-arabinose decreased with increasing l-arabinose concentration. The l-arabinose/l-ribulose/l-ribose ratio, with an initial l-arabinose concentration of 300 g/liter, was 71:6:23 after 4 h of reaction. To obtain near-equilibrium (54:14:32) at this high concentration of l-arabinose, more effective enzymes are required.Open in a separate windowFIG. 1.Effect of the ratio of AI to MPI on l-ribose production from l-arabinose by the purified AI and MPI from G. thermodenitrificans. Data are the means for three separate experiments, and error bars represent standard deviations. Symbols: •, l-ribose; ▪, l-ribulose.Open in a separate windowFIG. 2.(A) Effect of enzyme concentration on l-ribose production from l-arabinose at the optimal unit ratio (AI/MPI ratio, 1:2.5). Symbols: •, l-ribose; ▪, l-ribulose; ○, l-arabinose. (B) Effect of l-arabinose concentration on l-ribose production. Symbols: •, l-ribose; ▪, l-ribulose. Data are the means for three separate experiments, and error bars represent standard deviations.A time course reaction of l-ribose production from l-arabinose was monitored for 3 h with 8 U/ml AI and 20 U/ml MPI (Fig. ​(Fig.3).3). As a result, 118 g/liter l-ribose was obtained from an initial l-arabinose concentration of 500 g/liter after 3 h, with a conversion yield of 23.6% and a productivity of 39.3 g liter⁻¹ h⁻¹. Recombinant E. coli containing MDH yielded 52 g/liter l-ribose from an initial ribitol concentration of 100 g/liter after 72 h, with a productivity of 0.72 g liter⁻¹ h⁻¹ (14). The production and productivity obtained in the current study using AI and MPI from G. thermodenitrificans were 2.3- and 55-fold higher, respectively, than those obtained from ribitol and 17- and 21-fold higher than those obtained with the production of l-ribose from l-arabinose using resting cells of recombinant Lactobacillus plantarum (5). The chemical synthetic method is capable of producing 56.5 g/liter l-ribose from 250 g/liter l-arabinose after 3 h, corresponding to a productivity of 18.8 g liter⁻¹ h⁻¹ (6). Still, both the production and productivity of l-ribose using the method described herein were 2.1-fold higher. Thus, the method of production of l-ribose in the present study exhibited the highest productivity and production, compared to other fermentation methods and chemical syntheses.Open in a separate windowFIG. 3.Time course of l-ribose production from l-arabinose by purified AI and MPI from G. thermodenitrificans. Data are the means for three separate experiments, and error bars represent standard deviations. Symbols: •, l-ribose; ▪, l-ribulose; ○, l-arabinose.Several rounds of conversion reusing the cross-linked enzymes were performed (Fig. ​(Fig.4).4). The immobilized enzymes showed more than 20% conversion of l-ribose from l-arabinose for the 9th batch, and the concentration of l-ribose was reduced to 43% after the 20th batch. These results suggest that the immobilization of enzyme facilitates separation of product and enzyme, and it enables the enzyme to function continuously, as reported previously (3, 8, 12). Thus, the reuse of enzyme by immobilization improves the economic viability of this enzymatic process.Open in a separate windowFIG. 4.Reuse of immobilized AI and MPI from G. thermodenitrificans for l-ribose production from 100 g/liter l-arabinose. Data are the means for three separate experiments, and error bars represent standard deviations.     

Myocardial performance index in female athletes

Background

Long-term intensive training leads to morphological and mechanical changes in the heart generally known as “athlete’s heart”. Previous studies have suggested that the diastolic and systolic function of the ventricles is unaltered in athletes compared to sedentary.The purpose of this study was to investigate myocardial performance index (MPI) by pulsed wave Doppler (PWD) and by tissue Doppler imaging (TDI) in female elite athletes compared to sedentary controls.

Methods

The study consisted of 32 athletes (mean age 20 ± 2 years) and 34 sedentary controls (mean age 23 ± 2 years). MPI by PWD and TDI were measured in the left (LV) and right ventricle (RV) in both groups. Moreover, comparisons of MPI by the two methods and between the LV and RV within the two groups were made.

Results

There were no significant differences in MPI between athletes and controls (p > 0.05), whereas the LV had significantly higher MPI compared to RV (p < 0.001, in athletes and controls). The agreement and the correlation between the two methods measuring MPI showed low agreement and no correlation (athletes RV r = ?0.027, LV r = 0.12; controls RV r = 0.20, LV r = 0.30).

Conclusion

The global function of the LV and RV measured by MPI with PWD and TDI is similar in female athletes compared to sedentary controls. Conversely, both MPI by PWD and by TDI shows a significant difference between the LV and RV. However, the agreement and correlation between conventional methods of measuring MPI by PWD compared to MPI by TDI is very poor in both these populations.

     

Iron Oxide Nanoparticle-Micelles (ION-Micelles) for Sensitive (Molecular) Magnetic Particle Imaging and Magnetic Resonance Imaging

Background

Iron oxide nanoparticles (IONs) are a promising nanoplatform for contrast-enhanced MRI. Recently, magnetic particle imaging (MPI) was introduced as a new imaging modality, which is able to directly visualize magnetic particles and could serve as a more sensitive and quantitative alternative to MRI. However, MPI requires magnetic particles with specific magnetic properties for optimal use. Current commercially available iron oxide formulations perform suboptimal in MPI, which is triggering research into optimized synthesis strategies. Most synthesis procedures aim at size control of iron oxide nanoparticles rather than control over the magnetic properties. In this study, we report on the synthesis, characterization and application of a novel ION platform for sensitive MPI and MRI.

Methods and Results

IONs were synthesized using a thermal-decomposition method and subsequently phase-transferred by encapsulation into lipidic micelles (ION-Micelles). Next, the material and magnetic properties of the ION-Micelles were analyzed. Most notably, vibrating sample magnetometry measurements showed that the effective magnetic core size of the IONs is 16 nm. In addition, magnetic particle spectrometry (MPS) measurements were performed. MPS is essentially zero-dimensional MPI and therefore allows to probe the potential of iron oxide formulations for MPI. ION-Micelles induced up to 200 times higher signal in MPS measurements than commercially available iron oxide formulations (Endorem, Resovist and Sinerem) and thus likely allow for significantly more sensitive MPI. In addition, the potential of the ION-Micelle platform for molecular MPI and MRI was showcased by MPS and MRI measurements of fibrin-binding peptide functionalized ION-Micelles (FibPep-ION-Micelles) bound to blood clots.

Conclusions

The presented data underlines the potential of the ION-Micelle nanoplatform for sensitive (molecular) MPI and warrants further investigation of the FibPep-ION-Micelle platform for in vivo, non-invasive imaging of fibrin in preclinical disease models of thrombus-related pathologies and atherosclerosis.     

A framework for characterizing overlap of communication and computation in parallel applications

Effective overlap of computation and communication is a well understood technique for latency hiding and can yield significant performance gains for applications on high-end computers. In this paper, we propose an instrumentation framework for message-passing systems to characterize the degree of overlap of communication with computation in the execution of parallel applications. The inability to obtain precise time-stamps for pertinent communication events is a significant problem, and is addressed by generation of minimum and maximum bounds on achieved overlap. The overlap measures can aid application developers and system designers in investigating scalability issues. The approach has been used to instrument two MPI implementations as well as the ARMCI system. The implementation resides entirely within the communication library and thus integrates well with existing approaches that operate outside the library. The utility of the framework is demonstrated by analyzing communication-computation overlap for micro-benchmarks and the NAS benchmarks, and the insights obtained are used to modify the NAS SP benchmark, resulting in improved overlap.

Effect of food intake on myocardial performance index

Background

Myocardial performance index (MPI) has been investigated in a variety of populations, but the effect of food intake has not been evaluated. We assessed whether myocardial performance index is affected by food intake in healthy subjects.

Methods

Twenty-three healthy subjects aged 25.6?±?4.5 years were investigated. MPI was measured before, 30 min after, and 110 min after a standardized meal.

Results

MPI decreased significantly (P?<?0.05) from fasting values 30 min after the meal, and had almost returned to baseline after 110 min. MPI decreased from 0.28?±?0.06 (fasting) to 0.20?±?0.07 30 min after eating. At 110 min after eating the index value was almost back to the baseline value 0.26?±?0.06. (P?=?0.15).

Conclusions

This study shows that myocardial performance index is affected by food intake in healthy subjects.

     

Escher-FBA: a web application for interactive flux balance analysis

Background

Flux balance analysis (FBA) is a widely-used method for analyzing metabolic networks. However, most existing tools that implement FBA require downloading software and writing code. Furthermore, FBA generates predictions for metabolic networks with thousands of components, so meaningful changes in FBA solutions can be difficult to identify. These challenges make it difficult for beginners to learn how FBA works.

Results

To meet this need, we present Escher-FBA, a web application for interactive FBA simulations within a pathway visualization. Escher-FBA allows users to set flux bounds, knock out reactions, change objective functions, upload metabolic models, and generate high-quality figures without downloading software or writing code. We provide detailed instructions on how to use Escher-FBA to replicate several FBA simulations that generate real scientific hypotheses.

Conclusions

We designed Escher-FBA to be as intuitive as possible so that users can quickly and easily understand the core concepts of FBA. The web application can be accessed at https://sbrg.github.io/escher-fba.

     

Ambiguity and the evolution of the genetic code

The evolution of the genetic code is an extremely complex problem. The addition of a new method by which the code could evolve, however, allows much to be explained about the way in which the present codes (₃ and ₃ ) originated. The idea that ambiguity would allow the length of the codon to change is very useful, since it predicts the distribution of the 4-blocs and 2-blocs in the code, determines where variations in the code are probable, and presents a scenario for the evolution of the code.     

Experimental limitations in microdosimetry measurements using the variance technique

Summary Microdosimetry measurements give information about the energy imparted to a volume of given size. With the most frequent method only data for object sizes above 0.2 µm are obtainable. Although restricted to the dose mean values, the variance technique can, however, be applied to object sizes an order of magnitude less. In this report some limiting parameters for this technique are discussed and results down to about 20 nm in a⁶⁰co-ray beam are reported. The resulting data exceed earlier reported values at object sizes below 0.1 µm, but are in good agreement for larger object sizes.     

Accessing and distributing EMBL data using CORBA (common object request broker architecture)

Background  

The EMBL Nucleotide Sequence Database is a comprehensive database of DNA and RNA sequences and related information traditionally made available in flat-file format. Queries through tools such as SRS (Sequence Retrieval System) also return data in flat-file format. Flat files have a number of shortcomings, however, and the resources therefore currently lack a flexible environment to meet individual researchers' needs. The Object Management Group's common object request broker architecture (CORBA) is an industry standard that provides platform-independent programming interfaces and models for portable distributed object-oriented computing applications. Its independence from programming languages, computing platforms and network protocols makes it attractive for developing new applications for querying and distributing biological data.     

NT-proBNP and circulating inflammation markers in prediction of a normal myocardial scintigraphy in patients with symptoms of coronary artery disease

Background

Myocardial perfusion imaging (MPI) can detect myocardial perfusion abnormalities but many examinations are without pathological findings. This study examines whether circulating biomarkers can be used as screening modality prior to MPI.

Methodology/Principal Findings

243 patients with an intermediate risk of CAD or with known CAD with renewed suspicion of ischemia were referred to MPI. Blood samples were analyzed for N-terminal fragment of the prohormone brain natriuretic peptide (NT-proBNP), YKL-40, IL-6, matrix metalloproteinase 9 (MMP-9) and high sensitive C-reactive protein (hsCRP). Patients with myocardial perfusion defects had elevated levels of NT-proBNP (p<0.0001), YKL-40 (p = 0.03) and IL-6 (p = 0.03) but not of hsCRP (p = 0.58) nor of MMP-9 (p = 0.14). The NT-proBNP increase was observed in both genders (p<0.0001), whereas YKL-40 (p = 0.005) and IL-6 (p = 0.02) were elevated only in men. A NT-proBNP cut off-concentration at 25 ng/l predicted a normal MPI with a negative predictive value >95% regardless of existing CAD.

Conclusions

20-25% of patients suspected of CAD could have been spared a MPI by using a NT-proBNP cut-off concentration at 25 ng/l with a negative predictive value >95%. NT-proBNP has the potential use of being a screening marker of CAD before referral of the patient to MPI.     

An indirect method for estimating 15N isotope fractionation during nitrogen fixation by a legume under field conditions

A new technique is proposed for measuring ¹⁵N isotope fractionation during N fixation that obviates some of the possible disadvantages of existing methods. Accurate calculation of N fixation by legumes using the ¹⁵N natural abundance technique requires a value for the isotopic composition of fixed N as an input. Isotopic fractionation in fixed N in legumes has usually been measured using N- free solution culture but results can vary with Rhizobium strain and growth conditions. The proposed method avoids these problems and can be used as an integral part of a field experiment for evaluating N fixation.The technique is essentially a process of adjusting values of ¹⁵ N for fixed N until % N fixation calculated by the ¹⁵N natural abundance method best matches % N fixation estimated by the ¹⁵N enrichment method. The use of high % N fixation values improves the sensitivity and reliability of the method.A field evaluation of this comparison technique using chickpea (Cicer arietinum L.) provided a ¹⁵N isotope fractionation factor (–2.37) for fixed N close to that obtained by N-free solution culture methods (–2.10). The availability of these two independent techniques allowed mutual corroboration of estimates of ¹⁵N isotope fractionation during N fixation.

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Groups Partitioning Over CORBA for Cooperative Work

Many examples illustrate the usefulness of group partitioning in distributed systems. The process group abstraction is a powerful tool for the development of fault-tolerant distributed applications. This solution is also particularly relevant to group entities sharing similar properties or stakes when applied to the field of cooperative work. When dealing with distributed applications, communication standards have evolved from socket-based interfaces to Remote Procedure Calls and nowadays, towards distributed object platforms like CORBA. This standard from the Object Management Group masks distribution and heterogeneity and provides a good basis for distributed application development. This paper presents a review of group mechanisms found in the literature then focuses on the implementation of groups over CORBA. An implementation of such a service over CORBA illustrates the impact of group auto-organization. Performance we obtain show that our service is efficient and provides good mechanisms to manage operations in a group.     

Predictors of severe stenosis at invasive coronary angiography in patients with normal myocardial perfusion imaging

Purpose

Normal myocardial perfusion imaging (MPI) is associated with excellent prognosis. However, in patients with persisting symptoms, it may be difficult to determine the patients in whom invasive angiography is justified to rule out false negative MPI. We evaluated predictors for severe stenosis at invasive angiography in patients with persisting symptoms after normal MPI.

Methods

229 consecutive patients with normal MPI, without previous bypass surgery, underwent invasive angiography within 6 months. Older age was defined as >65 years. Multivariable analyses were performed to adjust for differences in baseline variables.

Results

Mean age was 62?±?11 years, 48% were women. Severe stenosis was observed in 34%, and of these patients 60% had single-vessel disease (not left main coronary artery disease). After adjusting for several variables, including diabetes, smoking status, hypertension and hypercholesterolaemia, predictors of severe stenosis were male gender, odds ratio (OR) 2.7 (95% confidence interval (CI) 1.5–4.9), older age, OR 1.9 (95% CI 1.02–3.54) previous PCI, OR 2.0 (95% CI 1.0–4.3) and typical angina, OR 2.5 (95% CI 1.4–4.6).

Conclusions

Increasing age, male gender, previous PCI and typical symptoms are predictors of severe stenosis at invasive coronary angiography in patients with normal MPI. The majority of these patients have single-vessel disease.

     

The design and implementation of MPI collective operations for clusters in long-and-fast networks

Several MPI systems for Grid environment, in which clusters are connected by wide-area networks, have been proposed. However, the algorithms of collective communication in such MPI systems assume relatively low bandwidth wide-area networks, and they are not designed for the fast wide-area networks that are becoming available. On the other hand, for cluster MPI systems, a bcast algorithm by van de Geijn, et al. and an allreduce algorithm by Rabenseifner have been proposed, which are efficient in a high bi-section bandwidth environment. We modify those algorithms so as to effectively utilize fast wide-area inter-cluster networks and to control the number of nodes which can transfer data simultaneously through wide-area networks to avoid congestion. We confirmed the effectiveness of the modified algorithms by experiments using a 10 Gbps emulated WAN environment. The environment consists of two clusters, where each cluster consists of nodes with 1 Gbps Ethernet links and a switch with a 10 Gbps upper link. The two clusters are connected through a 10 Gbps WAN emulator which can insert latency. In a 10 millisecond latency environment, when the message size is 32 MB, the proposed bcast and allreduce are 1.6 and 3.2 times faster, respectively, than the algorithms used in existing MPI systems for Grid environment.

Parasitological,Hematological and Biochemical Characteristics of a Model of Hyper-microfilariaemic Loiasis (Loa loa) in the Baboon (Papio anubis)

Background

Loiasis, a filarial infection caused by Loa loa usually thought to cause relatively minor morbidity, can cause serious and often fatal reactions in patients carrying very high levels of circulating Loa loa microfilariae (mf) following administration of microfilaricidal drugs. An experimental model of this condition would greatly aid the definition of the optimal management of this important clinical presentation.

Methodology/Principle Findings

Fifteen baboons (Papio anubis) were infected with 600 infective larvae (L3) isolated from Chrysops vector flies. Animals were observed for any clinical changes; blood samples were collected every 1–2 months for 22 months, and analysed for parasitological, hematological and biochemical profiles using standard techniques. All animals became patent but remained clinically normal throughout the study. The parasitological pre-patent period was between 4–8 months, with a majority (60%) of animals becoming patent by 5 months post infection (MPI); all animals were patent by 8 MPI. Microfilarial loads increased steadily in all animals and reached a peak at 18 MPI. By 10 MPI >70% of animals had mf >8,000 mf/mL, and at 18 MPI >70% of animals had mf >30,000mf/mL with 50% of these animals with mf >50,000mf/mL. Absolute eosinophil, creatinine, Ca²⁺ and K⁺ levels were generally above normal values (NV). Positive associations were seen between microfilariaemia and eosinophilia, Hb, Ca²⁺, and gamma-GT values, whilst significant negative associations were seen between microfilariaemia and potassium, glucose and mononuclear leukocyte levels.

Conclusions

Infection of splenectomised baboons with L. loa can induce levels of circulating microfilariae, and corresponding haematological profiles, which parallel those seen in those humans in danger of the severe post-microfilariacide clinical responses. Utilization of this experimental model could contribute to the improved management of the loiasis related adverse responses in humans.