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A Bayesian system integrating expression data with sequence patterns for localizing proteins: comprehensive application to the yeast genome.

We develop a probabilistic system for predicting the subcellular localization of proteins and estimating the relative population of the various compartments in yeast. Our system employs a Bayesian approach, updating a protein's probability of being in a compartment, based on a diverse range of 30 features. These range from specific motifs (e.g. signal sequences or the HDEL motif) to overall properties of a sequence (e.g. surface composition or isoelectric point) to whole-genome data (e.g. absolute mRNA expression levels or their fluctuations). The strength of our approach is the easy integration of many features, particularly the whole-genome expression data. We construct a training and testing set of approximately 1300 yeast proteins with an experimentally known localization from merging, filtering, and standardizing the annotation in the MIPS, Swiss-Prot and YPD databases, and we achieve 75 % accuracy on individual protein predictions using this dataset. Moreover, we are able to estimate the relative protein population of the various compartments without requiring a definite localization for every protein. This approach, which is based on an analogy to formalism in quantum mechanics, gives better accuracy in determining relative compartment populations than that obtained by simply tallying the localization predictions for individual proteins (on the yeast proteins with known localization, 92% versus 74%). Our training and testing also highlights which of the 30 features are informative and which are redundant (19 being particularly useful). After developing our system, we apply it to the 4700 yeast proteins with currently unknown localization and estimate the relative population of the various compartments in the entire yeast genome. An unbiased prior is essential to this extrapolated estimate; for this, we use the MIPS localization catalogue, and adapt recent results on the localization of yeast proteins obtained by Snyder and colleagues using a minitransposon system. Our final localizations for all approximately 6000 proteins in the yeast genome are available over the web at: http://bioinfo.mbb.yale. edu/genome/localize.

Amino Acid Motifs↗

A radiographic and tomographic imaging system integrated into a medical linear accelerator for localization of bone and soft-tissue targets.

PURPOSE: Dose escalation in conformal radiation therapy requires accurate field placement. Electronic portal imaging devices are used to verify field placement but are limited by the low subject contrast of bony anatomy at megavoltage (MV) energies, the large imaging dose, and the small size of the radiation fields. In this article, we describe the in-house modification of a medical linear accelerator to provide radiographic and tomographic localization of bone and soft-tissue targets in the reference frame of the accelerator. This system separates the verification of beam delivery (machine settings, field shaping) from patient and target localization. MATERIALS AND METHODS: A kilovoltage (kV) x-ray source is mounted on the drum assembly of an Elekta SL-20 medical linear accelerator, maintaining the same isocenter as the treatment beam with the central axis at 90 degrees to the treatment beam axis. The x-ray tube is powered by a high-frequency generator and can be retracted to the drum-face. Two CCD-based fluoroscopic imaging systems are mounted on the accelerator to collect MV and kV radiographic images. The system is also capable of cone-beam tomographic imaging at both MV and kV energies. The gain stages of the two imaging systems have been modeled to assess imaging performance. The contrast-resolution of the kV and MV systems was measured using a contrast-detail (C-D) phantom. The dosimetric advantage of using the kV imaging system over the MV system for the detection of bone-like objects is quantified for a specific imaging geometry using a C-D phantom. Accurate guidance of the treatment beam requires registration of the imaging and treatment coordinate systems. The mechanical characteristics of the treatment and imaging gantries are examined to determine a localizing precision assuming an unambiguous object. MV and kV radiographs of patients receiving radiation therapy are acquired to demonstrate the radiographic performance of the system. The tomographic performance is demonstrated on phantoms using both the MV and the kV imaging system, and the visibility of soft-tissue targets is assessed. RESULTS AND DISCUSSION: Characterization of the gains in the two systems demonstrates that the MV system is x-ray quantum noise-limited at very low spatial frequencies; this is not the case for the kV system. The estimates of gain used in the model are validated by measurements of the total gain in each system. Contrast-detail measurements demonstrate that the MV system is capable of detecting subject contrasts of less than 0.1% (at 6 and 18 MV). A comparison of the kV and MV contrast-detail performance indicates that equivalent bony object detection can be achieved with the kV system at significantly lower doses (factors of 40 and 90 lower than for 6 and 18 MV, respectively). The tomographic performance of the system is promising; soft-tissue visibility is demonstrated at relatively low imaging doses (3 cGy) using four laboratory rats. CONCLUSIONS: We have integrated a kV radiographic and tomographic imaging system with a medical linear accelerator to allow localization of bone and soft-tissue structures in the reference frame of the accelerator. Modeling and experiments have demonstrated the feasibility of acquiring high-quality radiographic and tomographic images at acceptable imaging doses. Full integration of the kV and MV imaging systems with the treatment machine will allow on-line radiographic and tomographic guidance of field placement.

Animals↗

Computerized tracking of mammography patients: value of a radiology information system integrated with a personal-computer data base.

OBJECTIVE. We investigated the advantages of using a radiology information system as the primary data source for a mammographic patient-tracking system that is based on a personal-computer local-area network and that requires almost no data entry. HARDWARE AND SOFTWARE. Our mammographic data base is maintained on a file server that provides cross-platform access to both Macintosh and IBM-compatible personal computers. Locally developed software automatically transfers mammographic data from our radiology information system to the file server's mammographic data base. The data transferred include patients' demographics (e.g., hospital identification number, address, referring physician) and the complete mammographic report. With the use of specific terminology, the need for follow-up can be automatically gleaned from the mammographic report and coded within the data base. Graphically oriented, commercially available software provides easy access to this information from any personal computer on our department's network. The software provides considerable flexibility for searching and manipulating the data without the need for customized data-base programming. Redundant data entry and associated errors are drastically reduced, as are personnel requirements for maintaining the system. Relative to most commercial radiology information systems, a personal computer facilitates the steps involved in tracking patients and obtaining highly customized analyses of the mammographic data base. The data in the mammographic data base exactly match those in the hospital's registration data and are easily transferred to other personal-computer programs for ancillary processing. CONCLUSION. This technique is ideal for departments that use a general-purpose radiology information system for mammographic reporting, yet need a more powerful but user-friendly and low-cost method for tracking their mammography patients.

Female↗

Lab-on-valve system integrating a chemiluminescent entity and in situ generation of nascent bromine as oxidant for chemiluminescent determination of tetracycline.

A novel configuration of a lab-on-valve (LOV) system was fabricated and applied for chemiluminescence (CL) detection by integrating a demountable Z-type flow cell onto the LOV unit. A bismuthate immobilized microcolumn was incorporated in one port of the LOV for in situ oxidation of KBr and generation of bromine as oxidant for the bromine-hydrogen peroxide-tetracycline (TC) chemiluminescent reaction. The nascent bromine reacts with hydrogen peroxide and produces a weak CL signal, the intensity of which was significantly enhanced in the presence of TC following an energy-transfer mechanism. A novel procedure for tetracycline quantification was therefore developed based on the present system. When compared with the reported flow injection-CL methods for TC, this procedure not only provided an improved detection limit of 2.0 microg L(-)(1) but also minimized sample and reagent consumption. A linear range of 6.0-10 000 microg L(-)(1) was derived along with RSD values of 5.9 (at the concentration level of quantification limit) and 2.2% (at 50 microg L(-)(1)), and a sampling frequency of 120 h(-)(1) was achieved. The system was validated with a National Standard Procedure (GB/T 18932.4-2002, HPLC with UV detection) by measuring TC contents in commercial milk samples.

Bromine↗

Central and autonomic nervous system integration in emotion.

Emotions involve physiological responses that are regulated by the brain. The present paper reviews the empirical literature on central nervous system (CNS) and autonomic nervous system (ANS) concomitants of emotional states, with a focus on studies that simultaneously assessed CNS and ANS activity. The reviewed data support two primary conclusions: (1) numerous cortical and subcortical regions show co-occurring activity with ANS responses in emotion, and (2) there may be reversed asymmetries on cortical and subcortical levels with respect to CNS/ANS interrelations. These observations are interpreted in terms of a model of neurovisceral integration in emotion, and directions for future research are presented.

Affect↗

MPSA: integrated system for multiple protein sequence analysis with client/server capabilities.

UNLABELLED: MPSA is a stand-alone software intended to protein sequence analysis with a high integration level and Web clients/server capabilities. It provides many methods and tools, which are integrated into an interactive graphical user interface. It is available for most Unix/Linux and non-Unix systems. MPSA is able to connect to a Web server (e.g. http://pbil.ibcp.fr/NPSA) in order to perform large-scale sequence comparison on up-to-date databanks. AVAILABILITY: Free to academic http://www.ibcp.fr/mpsa/ CONTACT: c.blanchet@ibcp.fr

Computing Methodologies↗

Thrombomodulin-protein C-EPCR system: integrated to regulate coagulation and inflammation.

Late in the 18th century, William Hewson recognized that the formation of a clot is characteristic of many febrile, inflammatory diseases (Owen C. A History of Blood Coagulation. Rochester, Minnesota: Mayo Foundation; 2001). Since that time, there has been steady progress in our understanding of coagulation and inflammation, but it is only in the past few decades that the molecular mechanisms linking these 2 biologic systems have started to be delineated. Most of these can be traced to the vasculature, where the systems most intimately interact. Thrombomodulin (TM), a cell surface-expressed glycoprotein, predominantly synthesized by vascular endothelial cells, is a critical cofactor for thrombin-mediated activation of protein C (PC), an event further amplified by the endothelial cell protein C receptor (EPCR). Activated PC (APC), in turn, is best known for its natural anticoagulant properties. Recent evidence has revealed that TM, APC, and EPCR have activities that impact not only on coagulation but also on inflammation, fibrinolysis, and cell proliferation. This review highlights recent insights into the diverse functions of this complex multimolecular system and how its components are integrated to maintain homeostasis under hypercoagulable and/or proinflammatory stress conditions. Overall, the described advances underscore the usefulness of elucidating the relevant molecular pathways that link both systems for the development of novel therapeutic and diagnostic targets for a wide range of inflammatory diseases.

Animals↗

An integrated system for the non-invasive assessment of vessel wall and hemodynamic properties of large arteries by means of ultrasound.

OBJECTIVES: To integrate methods for non-invasive assessment of vessel wall properties (diastolic diameter, distension waveform and intima-media thickness) and hemodynamic properties (blood flow velocity and shear rate distribution) of large arteries by means of dedicated ultrasound signal processing. METHODS: we have developed an arterial laboratory (ART-lab) system. ART-lab consists of software running on a standard personal computer, equipped with a data acquisition card for the acquisition of radio frequency (RF) ultrasound signals obtained with a conventional echo scanner. It operates either (1) off-line or (2) in real-time. Real-time operation is restricted to the assessment of vessel wall properties because of limitations in computational power. RESULTS: This paper provides an overview of ART-lab ultrasound radio frequency data acquisition and dedicated RF-signal processing methods. The capabilities of the system are illustrated with some typical applications. CONCLUSIONS: ART-lab in real-time mode is a useful tool for monitoring arterial vessel wall dynamics, while off-line it can be employed to investigate the elastic vessel wall properties in combination with hemodynamics, such as blood flow velocity and shear rate distribution.

Arteries↗