PathoGene: a pathogen coding sequence discovery and analysis resource

PathoGene is a web-based resource that streamlines the process of predicting genes in microorganisms and designs PCR primers for amplification to facilitate sequence analysis and experimentation. PathoGene currently supports primer design for every complete microbial, viral, and fungal genome as cataloged in GenBank by the National Center for Biotechnology Information (NCBI; http://www.ncbi.nlm.nih.gov/). The resulting primers can then be subjected to a stand-alone Basic Local Alignment Search Tool (BLAST) system called PathoBLAST in which the predicted PCR product and/or primers can be compared against the genome of interest or a similar genome to find related genes or estimate primer quality.     

UniCarb-DB: a database resource for glycomic discovery

Glycosylation is one of the most important post-translational modifications of proteins, known to be involved in pathogen recognition, innate immune response and protection of epithelial membranes. However, when compared to the tools and databases available for the processing of high-throughput proteomic data, the glycomic domain is severely lacking. While tools to assist the analysis of mass spectrometry (MS) and HPLC are continuously improving, there are few resources available to support liquid chromatography (LC)-MS/MS techniques for glycan structure profiling. Here, we present a platform for presenting oligosaccharide structures and fragment data characterized by LC-MS/MS strategies. The database is annotated with high-quality datasets and is designed to extend and reinforce those standards and ontologies developed by existing glycomics databases. AVAILABILITY: http://www.unicarb-db.org     

Design of a nonuniformly distributed biocatalyst

The properties of a nonuniformly distributed biocatalyst, where the active enzymes are immobilized on the exterior or the interior portions o a solid support, are compared with those of a conventional biocatalyst which is uniformly distributed in a spherical geometry. To investigate the performance of nonuniformly distributed biocatalysts their effectiveness factors are computed and compared for six different enzyme distribution configurations: one-half core, one-half shell, one-third center space, one-third middle annulus, one-third outer shell, and the uniformly distributed. According to the results of numerical analysis, the biocatalyst performance of the exterior "shell" configuration is always far more effective for the immobilized enzymes with positive order reaction kinetics such as Michaelis-Menten and competitive product inhibition. However, in the case of negative order enzymatic reaction kinetics such as substrate inhibition, the interior "core" configuration of the biocatalyst can render far greater enzyme utilization efficiency.     

Direct queries for discovering network resource properties in a distributed environment

The development and performance of networkaware applications depends on the availability of accurate predictions of network resource properties. Obtaining this information directly from the network is a scalable solution that provides the accurate performance predictions and topology information needed for planning and adapting application behavior across a variety of networks. The performance predictions obtained directly from the network are as accurate as applicationlevel benchmarks, but the networkbased technique provides the added advantages of scalability and topology discovery. We describe how to determine network properties directly from the network using SNMP. We provide an overview of SNMP and describe the features it provides that make it possible to extract both available bandwidth and network topology information from network devices. The available bandwidth predictions based on network queries using SNMP are compared with traditional predictions based on application history to demonstrate that they are equally useful. To demonstrate the feasibility of topology discovery, we present results for a large Ethernet LAN.     

TILLMore, a resource for the discovery of chemically induced mutants in barley

A sodium azide-mutagenized population of barley (cv. 'Morex') was developed and utilized to identify mutants at target genes using the 'targeting induced local lesions in genomes' (TILLING) procedure. Screening for mutations at four agronomically important genes (HvCO1, Rpg1, eIF4E and NR) identified a total of 22 new mutant alleles, equivalent to the extrapolated rate of one mutation every 374 kb. All mutations except one were G/C to A/T transitions and several (approximately 68%) implied a change in protein amino acid sequence and therefore a possible effect on phenotype. The high rate of mutation detected through TILLING is in keeping with the high frequency (32.7%) of variant phenotypes observed amongst the M(3) families. Our results indicate the feasibility of using this resource for both reverse and forward genetics approaches to investigate gene function in barley and related crops.     

UniPep - a database for human N-linked glycosites: a resource for biomarker discovery

There has been considerable recent interest in proteomic analyses of plasma for the purpose of discovering biomarkers. Profiling N-linked glycopeptides is a particularly promising method because the population of N-linked glycosites represents the proteomes of plasma, the cell surface, and secreted proteins at very low redundancy and provides a compelling link between the tissue and plasma proteomes. Here, we describe UniPep http://www.unipep.org--a database of human N-linked glycosites--as a resource for biomarker discovery.     

Design and implementation of a distributed multimedia collaborative environment

Multimedia applications are being developed and used for many aspects of our lives today. New high-speed, broadband networks have emerged and made the operation of these high-bandwidth requiring applications readily feasible. However, the development of distributed multimedia applications and efficient and reliable operation of these applications are still very difficult. This paper presents a flexible and reliable distributed multimedia collaborative environment called MAESTRO which provides a rich multimedia collaborative service API and which provides distributed multimedia services that can be used to develop a variety of multimedia applications easily. MAESTRO has been designed using CORBA. The system as well as applications running on it are managed and controlled in order to provide a reliable and efficient multimedia operations environment. We validate our claim by developing a number of multimedia applications using our distributed multimedia system and by using them for supporting distributed collaborative scientific and engineering research experiments. This revised version was published online in July 2006 with corrections to the Cover Date.     

Manipulation of the mouse genome: a multiple impact resource for drug discovery and development

Few would deny that the pharmaceutical industry's investment in genomics throughout the 1990s has yet to deliver in terms of drugs on the market. The reasons are complex and beyond the scope of this review. The unique ability to manipulate the mouse genome, however, has already had a positive impact on all stages of the drug discovery process and, increasingly, on the drug development process too. We give an overview of some recent applications of so-called 'transgenic' mouse technology in pharmaceutical research and development. We show how genetic manipulation in the mouse can be employed at multiple points in the drug discovery and development process, providing new solutions to old problems.     

Design and discovery of metamorphic proteins

Metamorphic proteins are single amino acid sequences that reversibly interconvert between multiple, dramatically different native structures, often with distinct functions. Since the discovery of the first metamorphic proteins in the early 2000s, several additional metamorphic proteins have been identified, and it was suggested that up to 4% of proteins in the PDB may switch folds. Metamorphic proteins have been found to share common features such as marginal thermostability and inconsistencies in predicted secondary structures. Outstanding challenges in the field include the search for more metamorphic proteins and the design of new proteins that switch folds. Identification of novel metamorphic proteins in nature will improve therapeutic targeting of fold-switching proteins involved in human pathology and will enhance the design of protein-based therapies. Designed fold switching proteins have applications as biosensors, molecular switches, molecular machines, and self-assembling systems.     

Subdural grid recordings of distributed neocortical networks involved with somatosensory discrimination

Previous studies suggest that evidence for the sub-second activation of distributed neural networks can be obtained by computing the covariance between segments of the scalp-recorded evoked potential. However, the cortical representation of such potentials is not known. Here we report a case study where the evoked potential covariance (EPC) measure was applied to data recorded from a 58-channel subdural grid implanted in an epilepsy patient. Recordings were made while the patient performed a task that required judging the somatosensory intensities of electrical stimuli and executing precise finger flexion responses in response to a subset of those stimuli. Post-stimulus EPC patterns involved covariances between somatosensory, motor, and temporal regions. Pre-stimulus EPC patterns involved these same regions, but only when it could be anticipated that the upcoming stimulus would likely require a response. The majority of the observed EPCs occurred with non-zero time-lags, and these EPCs often involved non-adjacent electrode pairs. Thus, the observed EPCs were unlikely to arise solely from volume conduction. Rather, they appeared to reflect the transient integration of activity across distinct cortical processing nodes.     

Profiling services for resource optimization and capacity planning in distributed systems

The capacity needs of online services are mainly determined by the volume of user loads. For large-scale distributed systems running such services, it is quite difficult to match the capacities of various system components. In this paper, a novel and systematic approach is proposed to profile services for resource optimization and capacity planning. We collect resource consumption related measurements from various components across distributed systems and further search for constant relationships between these measurements. If such relationships always hold under various workloads along time, we consider them as invariants of the underlying system. After extracting many invariants from the system, given any volume of user loads, we can follow these invariant relationships sequentially to estimate the capacity needs of individual components. By comparing the current resource configurations against the estimated capacity needs, we can discover the weakest points that may deteriorate system performance. Operators can consult such analytical results to optimize resource assignments and remove potential performance bottlenecks. In this paper, we propose several algorithms to support capacity analysis and guide operator’s capacity planning tasks. Our algorithms are evaluated with real systems and experimental results are also included to demonstrate the effectiveness of our approach.

Prospects for riboswitch discovery and analysis

An expanding number of metabolite-binding riboswitch classes are being discovered in the noncoding portions of bacterial genomes. Findings over the last decade indicate that bacteria commonly use these RNA genetic elements as regulators of metabolic pathways and as mediators of changes in cell physiology. Some riboswitches are surprisingly complex, and they rival protein factors in their structural and functional sophistication. Each new riboswitch discovery expands our knowledge of the biochemical capabilities of RNA, and some give rise to new questions that require additional study to be addressed. Some of the greatest prospects for riboswitch research and some of the more interesting mysteries are discussed in this review.